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  • 1.
    Ahmad, Irma
    et al.
    Orebro Univ, Sweden.
    Sandberg, Matilda
    Orebro Univ, Sweden.
    Brus, Ole
    Orebro Univ, Sweden.
    Ekman, Carl Johan
    Karolinska Inst, Sweden.
    Hammar, Åsa
    Univ Bergen, Norway.
    Landén, Mikael
    Karolinska Institutet, Stockholm, Sweden; The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Lundberg, Johan
    Karolinska Inst, Sweden; Stockholm Health Care Services, Stockholm, Sweden.
    Nordanskog, Pia
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience.
    von Knorring, Lars
    Uppsala University, Uppsala, Sweden.
    Nordenskjöld, Axel
    Örebro University, Örebro, Sweden.
    Validity of diagnoses, treatment dates, and rating scales in the Swedish national quality register for electroconvulsive therapy2022In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 76, no 2, p. 96-103Article in journal (Refereed)
    Abstract [en]

    Background The Swedish national quality register for electroconvulsive therapy (Q-ECT) contains data on patients receiving treatment with electroconvulsive therapy (ECT) in Sweden. Aim This study determined the validity of diagnoses, treatment dates, and rating scales in the Q-ECT by investigating the degree of accordance between data from the Q-ECT and patient records. Materials and methods From January 2016 to December 2017, 200 treatment series were randomly selected from the Q-ECT. The corresponding patient records were requested from the treating hospitals. Data on the indicative diagnosis, dates for the first and the last ECT session, and rating scales were compared between the Q-ECT and patient records using (i) a strict and (ii) a liberal method of assessment. Using the liberal method, each variable was assessed as accordant if it belonged to the same diagnosis group, or if the dates differed by less than 1 week, or ratings differed by only 1 point on the Clinical Global Impression Scale (CGI- S), or no more than 3 points on the Montgomery angstrom sberg Depression Rating Scale between the Q-ECT and the patient record. Results A total of 179 patient records were received. The strict method of assessment showed an accordance of 89% or higher for all studied variables. The liberal method showed an accordance of 95% or higher. Conclusions We conclude that data on the studied variables in the Q-ECT have high validity. However, limited use of some rating scales makes the results uncertain. Measures can be taken to further improve the data quality.

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  • 2.
    Alm Mårtensson, Anna
    et al.
    Länsstyrelsen i Jönköping, Sverige.
    Boström, Anita
    Institutionen för hälsovetenskaper, Karlstads universitet, Sverige.
    Lindmark, Ulrika
    Jönköping University, HHJ, Avd. för naturvetenskap och biomedicin, Sverige.
    Lundgren, Charlie
    Länsstyrelsen Västerbotten, Sverige.
    Ludvigsson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine.
    Simmons, Johanna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Att möta våldsutsatta äldre personer2022In: Äldre personers utsatthet för våld i nära relationer: Interprofessionella perspektiv / [ed] Lena Östlund, Lund: Studentlitteratur AB , 2022, p. 183-220Chapter in book (Other academic)
  • 3.
    Aminoff, Victoria
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Bobeck, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Hjort, Sofia
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Sorliden, Elise
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Ludvigsson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Berg, Matilda
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Tailored internet-based psychological treatment for psychological problems during the COVID-19 pandemic: A randomized controlled trial2023In: Internet Interventions, ISSN 2214-7829, Vol. 34, article id 100662Article in journal (Refereed)
    Abstract [en]

    The COVID-19 pandemic influence mental health in both infected and non-infected populations. In this study we examined if individually tailored internet-based cognitive behavioral therapy (ICBT) could be an effective treatment for psychological symptoms related to the pandemic. Following recruitment we included 76 participants who were randomized to either a treatment group (n = 37) or a waitlist control group (n = 39). The treatment group received 8 modules (out of 16 possible) during 8 weeks with weekly therapist support. We collected data on symptoms of depression, experienced quality of life, anxiety, stress, anger, insomnia, PTSD, and alcohol use before, after the treatment and at one year follow-up. Using multiple regression analysis, group condition was found to be a statistically significant predictor for a decrease, favoring the treatment group, in symptoms of depression, insomnia, and anger with small to moderate effect sizes. The improvements remained at one year follow-up. Group condition did not significantly predict changing symptoms regarding experienced quality of life, anxiety, stress, PTSD and alcohol use. Findings indicate that ICBT is an effective intervention for some psychological symptoms associated with the COVID-19 pandemic. There is a need for further studies on mechanisms of change and on tailored ICBT for problems associated with crises like the pandemic.

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  • 4.
    Aminoff, Victoria
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Sellén, Malin
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Sörliden, Elise
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Ludvigsson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Health, Medicine and Caring Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Berg, Matilda
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Clinical Neuroscience, Karolinska Institute, Sweden.
    Internet-Based Cognitive Behavioral Therapy for Psychological Distress Associated With the COVID-19 Pandemic: A Pilot Randomized Controlled Trial2021In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 12, article id 684540Article in journal (Refereed)
    Abstract [en]

    Background: The COVID-19 pandemic has been associated with various negative psychological consequences. This is a challenge for the society as regular psychological services cannot be offered to the same extent as before the pandemic. In addition to the requirement of social distancing, there is a need to adjust psychological treatment components like exposure to avoid increasing the spread of the infection. Internet-delivered cognitive behavior therapy (ICBT) has an established evidence base for a range of psychiatric problems and has been suggested as one possible approach to deal with the situation. This study aimed to conduct a randomized controlled pilot trial during the summer of 2020 with a broad focus on psychological distress and a treatment approach that tailors the intervention based on symptom profile and preferences.

    Methods: Following the advertisement and interview, we included 52 participants with elevated levels of psychological distress. They were randomly allocated to either a 7-week-long individually tailored ICBT (n = 26) or a wait-list control condition (n = 26). Measures of depression and quality of life were used as primary outcomes. We also included secondary outcome measures of anxiety, insomnia, trauma, stress, anger, and alcohol use. For screening, we used the CoRonavIruS Health Impact Survey (CRISIS).

    Results: Overall moderate to large between-group effects were found at post-treatment in favor of the treatment on measures of both depression [Beck Depression Inventory (BDI); Cohens d = 0.63; Patient Health Questionnaire (PHQ-9): d = 0.62] and anxiety [Generalized Anxiety Disorder-7-item scale (GAD-7); d = 0.82]. This was also observed for stress symptoms [Perceived Stress Scale (PSS-14); d = 1.04]. No effects were seen on measures of quality of life, insomnia, symptoms of post-traumatic stress, and anger. There was an effect on alcohol use [Alcohol Use Disorder Identification Test (AUDIT); d = 0.54], which was not of clinical relevance.

    Conclusion: Individually tailored ICBT shows initial promise as a way to reduce psychological problems in association with the COVID-19 pandemic. A possible limitation was that the trial was conducted when the effects of the pandemic were decreasing and when fewer people were affected by the restrictions (e.g., the summer of 2020).

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  • 5.
    Andersson, Gerhard
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Käll, Anton
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Juhlin, Simon
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Wahlstrom, Carl
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Licht, Edvard de Fine
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Färdeman, Simon
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Franck, Anna
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Tholcke, Anna
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Nachtweij, Karin
    Linnaeus Univ, Sweden.
    Fransson, Emma
    Linnaeus Univ, Sweden.
    Vernmark, Kristofer
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Ludvigsson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Berg, Matilda
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Free choice of treatment content, support on demand and supervision in internet-delivered CBT for adults with depression: A randomized factorial design trial2023In: Behaviour Research and Therapy, ISSN 0005-7967, E-ISSN 1873-622X, Vol. 162, article id 104265Article in journal (Refereed)
    Abstract [en]

    Even if much is known regarding the effects of internet-delivered cognitive behaviour therapy (ICBT) for depression there are several topics that have not been studied. In this factorial design trial with 197 participants we investigated if clients in ICBT could select treatment modules themselves based on a selection of 15 tailored treatment modules developed for use in ICBT for depression. We contrasted this against clinician-tailored module selection. We also investigated if support on demand (initiated by the client) could work as well as scheduled support. Finally, we tested if clients that were mentioned in supervision would improve more than clients not mentioned (with the exception of acute cases). The treatment period lasted for 10 weeks, and we measured effects at post-treatment and two-year follow-up. Measures of depression and secondary outcomes were collected at pre-treatment, post-treatment and two-year follow-up. Overall, within-group effects were large across con-ditions (e.g., d = 1.73 on the BDI-II). We also found a small but significant difference in favour of self-tailored treatment over clinician-tailored (d = 0.26). Within-group effects for the secondary measures were all moderate to large including a test of knowledge about CBT. The other two contrasts "support on demand" and "supervision" yielded mostly non-significant differences, with the exception of a larger dropout rate in the support on demand condition. There were few negative effects (2.2%). Effects were largely maintained at a two-year follow-up. We conclude that clients can choose treatment modules and that support on demand may work. The role of su-pervision is not yet clear as advice can be transferred across clients.

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  • 6.
    Axfors, Cathrine
    et al.
    Uppsala Univ, Sweden.
    Iliadis, Stavros I.
    Uppsala Univ, Sweden.
    Rasmusson, Lovisa L.
    Uppsala Univ, Sweden.
    Beckman, Ulrika
    Sodra Alvsborgs Hosp, Sweden.
    Fazekas, Attila
    Lund Univ, Sweden.
    Frisén, Louise
    Karolinska Inst, Sweden.
    Sandström, Lotta
    Umea Univ, Sweden.
    Thelin, Nils
    Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Wahlberg, Jeanette
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine.
    Skalkidou, Alkistis
    Uppsala Univ, Sweden.
    Papadopoulos, Fotios C.
    Uppsala Univ, Sweden.
    Preferences for Gender Affirming Treatment and Associated Factors Among Transgender People in Sweden2023In: Sexuality Research & Social Policy, ISSN 1868-9884, E-ISSN 1553-6610, Vol. 20, p. 479-490Article in journal (Refereed)
    Abstract [en]

    Introduction Gender affirming surgery of primary and/or secondary sex characteristics has been shown to alleviate gender dysphoria. A descriptive snapshot of current treatment preferences is useful to understand the needs of the transgender population seeking health care. This study aimed to describe preferences for gender affirming treatment, and their correlates, among individuals seeking health care for gender dysphoria in Sweden after major national legislative reforms. Methods Cross-sectional study where transgender patients (n = 232) recruited from all six Gender Dysphoria centers in Sweden 2016-2019, answered a survey on treatment preferences and sociodemographic, health, and gender identity-related information during the same time-period. Factors associated with preferring top surgery (breast augmentation or mastectomy), genital surgery, and other surgery (e.g., facial surgery) were examined in univariable and multivariable regression analyses in the 197 people without prior such treatment. Main study outcomes were preferences for feminizing or masculinizing hormonal and surgical gender affirming treatment. Results The proportion among birth assigned male and assigned female patients preferring top surgery was 55.6% and 88.7%, genital surgery 88.9% and 65.7%, and other surgery (e.g., facial surgery) 85.6% and 22.5%, respectively. Almost all participants (99.1%) wanted or had already received hormonal treatment and most (96.7%) wished for some kind of surgical treatment; 55.0% wanted both top and genital surgery. Preferring a binary pronoun (he/she) and factors indicating more severe gender incongruence were associated with a greater wish for surgical treatment. Participants with somatic comorbidities were less likely to want genital surgery, while aF with lacking social support were less likely to want internal genital surgery, in the multivariable analyses. Conclusions In this sample of Swedish young adults seeking health care for gender dysphoria, preferences for treatment options varied according to perceived gender identity. Policy Implications The study findings underline the need for individualized care and flexible gender affirming treatment options. The role of somatic comorbidities should be further explored, and support should be offered to transgender people in need. There is an unmet need for facial surgery among aM.

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  • 7.
    Backberg, Matilda
    et al.
    RISE Res Inst Sweden, Sweden.
    Vikingsson, Svante
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, SE-58758 Linkoping, Sweden; RTI Int, NC 27709 USA.
    Strandberg, Joakim
    Publ Hlth Agcy Sweden, Sweden.
    Wall, Sara
    Publ Hlth Agcy Sweden, Sweden.
    Åstrand, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Hanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Persson, Mattias
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, SE-58758 Linkoping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, SE-58758 Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, SE-58758 Linkoping, Sweden.
    Using in vitro receptor activity studies of synthetic cannabinoids to support the risk assessment of new psychoactive substances-A Swedish strategy to protect public health from harm2023In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 348, article id 111691Article in journal (Refereed)
    Abstract [en]

    In the past 15 years, close to 1000 of new psychoactive substances (NPS) have been reported in Europe and globally. At the time of identification, data on safety, toxicity and carcinogenic potential of many NPS are not available or very limited. To work more efficiently, a strategy and collaboration between the Public Health Agency of Sweden (PHAS) and the National Board of Forensic Medicine was established involving in vitro receptor activity assays to demonstrate neurological activity of NPS. This report summarizes the first results on the synthetic cannabinoid receptor agonists (SCRAs), and subsequent actions taken by PHAS. A total of 18 potential SCRAs were selected by PHAS for in vitro pharmacological characterization. 17 compounds could be acquired and investigated for their activity on the human cannabinoid-1 (CB1) receptors expressed together with the AequoScreen system in CHO-K1 cells. Dose-response curves were established using eight different concentrations in triplicates at three occasions with JWH-018 as reference. For the MDMB-4enPINACA, MMB-022, ACHMINACA, ADB-BUTINACA, 5F-CUMYL-PeGACLONE, 5C-AKB48, NM-2201, 5FCUMYL-PINACA, JWH-022, 5Cl-AB-PINACA, MPhP-2201, 5F-AKB57 the half maximal effective concentration values ranged from 2.2 nM (5F-CUMYL-PINACA) to 171 nM (MMB-022). EG-018 and 3,5-AB-CHMFUPPYCA were none-active. The results contributed to 14 of these compounds being scheduled as narcotics in Sweden. In conclusion, many of the emerging SCRAs are potent activators of the CB1 receptor in vitro, although some lack activity or are partial agonists. The new strategy proved useful when data on psychoactive effects of the SCRAs under investigation were not available or limited. (c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

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  • 8.
    Barbier, Estelle
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Barchiesi, Riccardo
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Domi, Ana
    Univ Gothenburg, Sweden.
    Chanthongdee, Kanat
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Mahidol Univ, Thailand.
    Domi, Esi
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Gaëlle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Xu, Li
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Sichuan Prov Peoples Hosp, Peoples R China.
    Adermark, Louise
    Univ Gothenburg, Sweden.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Downregulation of Synaptotagmin 1 in the Prelimbic Cortex Drives Alcohol-Associated Behaviors in Rats2021In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 89, no 4, p. 398-406Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Alcohol addiction is characterized by persistent neuroadaptations in brain structures involved in motivation, emotion, and decision making, including the medial prefrontal cortex, the nucleus accumbens, and the amygdala. We previously reported that induction of alcohol dependence was associated with long-term changes in the expression of genes involved in neurotransmitter release. Specifically, Syt1, which plays a key role in neurotransmitter release and neuronal functions, was downregulated. Here, we therefore examined the role of Syt1 in alcohol-associated behaviors in rats. METHODS: We evaluated the effect of Syt1 downregulation using an adeno-associated virus (AAV) containing a short hairpin RNA against Syt1. Cre-dependent Syt1 was also used in combination with an rAAV2 retro-Cre virus to assess circuit-specific effects of Syt1 knockdown (KD). RESULTS: Alcohol-induced downregulation of Syt1 is specific to the prelimbic cortex (PL), and KD of Syt1 in the PL resulted in escalated alcohol consumption, increased motivation to consume alcohol, and increased alcohol drinking despite negative consequences ("compulsivity"). Syt1 KD in the PL altered the excitation/inhibition balance in the basolateral amygdala, while the nucleus accumbens core was unaffected. Accordingly, a projection-specific Syt1 KD in the PL-basolateral amygdala projection was sufficient to increase compulsive alcohol drinking, while a KD of Syt1 restricted to PL-nucleus accumbens core projecting neurons had no effect on tested alcohol-related behaviors. CONCLUSIONS: Together, these data suggest that dysregulation of Syt1 is an important mechanism in long-term neuroadaptations observed after a history of alcohol dependence, and that Syt1 regulates alcohol-related behaviors in part by affecting a PL-basolateral amygdala brain circuit.

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  • 9.
    Barchiesi, Riccardo
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Chanthongdee, Kanat
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Mahidol Univ, Thailand.
    Domi, Esi
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Gobbo, Francesco
    Univ Edinburgh, Scotland.
    Coppola, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Toivainen, Sanne
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Holm, Lovisa
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Gaëlle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Xu, Li
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Elect Sci & Technol China, Peoples R China.
    Augier, Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Barbier, Estelle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Stress-induced escalation of alcohol self-administration, anxiety-like behavior, and elevated amygdala Avp expression in a susceptible subpopulation of rats2021In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, Vol. 26, no 5, article id e13009Article in journal (Refereed)
    Abstract [en]

    Comorbidity between alcohol use and anxiety disorders is associated with more severe symptoms and poorer treatment outcomes than either of the conditions alone. There is a well-known link between stress and the development of these disorders, with post-traumatic stress disorder as a prototypic example. Post-traumatic stress disorder can arise as a consequence of experiencing traumatic events firsthand and also after witnessing them. Here, we used a model of social defeat and witness stress in rats, to study shared mechanisms of stress-induced anxiety-like behavior and escalated alcohol self-administration. Similar to what is observed clinically, we found considerable individual differences in susceptibility and resilience to the stress. Both among defeated and witness rats, we found a subpopulation in which exposure was followed by emergence of increased anxiety-like behavior and escalation of alcohol self-administration. We then profiled gene expression in tissue from the amygdala, a key brain region in the regulation of stress, alcohol use, and anxiety disorders. When comparing "comorbid" and resilient socially defeated rats, we identified a strong upregulation of vasopressin and oxytocin, and this correlated positively with the magnitude of the alcohol self-administration and anxiety-like behavior. A similar trend was observed in comorbid witness rats. Together, our findings provide novel insights into molecular mechanisms underpinning the comorbidity of escalated alcohol self-administration and anxiety-like behavior.

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  • 10.
    Barchiesi, Riccardo
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Chanthongdee, Kanat
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Mahidol Univ, Thailand.
    Petrella, Michele
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Xu, Li
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Söderholm, Simon
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Domi, Esi
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Gaëlle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Coppola, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Wiskerke, Joost
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Szczot, Ilona
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Domi, Ana
    Univ Gothenburg, Sweden.
    Adermark, Louise
    Univ Gothenburg, Sweden.
    Augier, Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Cantù, Claudio
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Barbier, Estelle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    An epigenetic mechanism for over-consolidation of fear memories2022In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 27, no 12, p. 4893-4904Article in journal (Refereed)
    Abstract [en]

    Excessive fear is a hallmark of anxiety disorders, a major cause of disease burden worldwide. Substantial evidence supports a role of prefrontal cortex-amygdala circuits in the regulation of fear and anxiety, but the molecular mechanisms that regulate their activity remain poorly understood. Here, we show that downregulation of the histone methyltransferase PRDM2 in the dorsomedial prefrontal cortex enhances fear expression by modulating fear memory consolidation. We further show that Prdm2 knock-down (KD) in neurons that project from the dorsomedial prefrontal cortex to the basolateral amygdala (dmPFC-BLA) promotes increased fear expression. Prdm2 KD in the dmPFC-BLA circuit also resulted in increased expression of genes involved in synaptogenesis, suggesting that Prdm2 KD modulates consolidation of conditioned fear by modifying synaptic strength at dmPFC-BLA projection targets. Consistent with an enhanced synaptic efficacy, we found that dmPFC Prdm2 KD increased glutamatergic release probability in the BLA and increased the activity of BLA neurons in response to fear-associated cues. Together, our findings provide a new molecular mechanism for excessive fear responses, wherein PRDM2 modulates the dmPFC -BLA circuit through specific transcriptomic changes.

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  • 11.
    Berg, Matilda
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Lindegaard, Tomas
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Flygare, Anna
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Sjöbrink, Julia
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Hagvall, Linn
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Palmebäck, Sofia
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Klemetz, Helena
    Psykologpartners, Private practice, Linköping, Sweden.
    Ludvigsson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Internet-based CBT for adolescents with low self-esteem: a pilot randomized controlled trial2022In: Cognitive Behaviour Therapy, ISSN 1650-6073, E-ISSN 1651-2316, Vol. 51, no 5, p. 388-407Article in journal (Refereed)
    Abstract [en]

    Low self-esteem is a common problem among adolescents and is related to psychiatric problems such as depression and anxiety. However, effective and available interventions primarily targeting low self-esteem are scarce, in particular for youths. To address this gap, the aim of this pilot study was to evaluate a novel internet-based Cognitive Behavioral Therapy (ICBT) program for low self-esteem in adolescents using a randomized controlled design. Fifty-two participants (15-19 years) were recruited and randomly allocated to seven weeks of therapist-supported ICBT (n=26) or to a waitlist control condition (n=26). The primary outcome was the Rosenberg Self-Esteem Scale (RSES). Secondary outcomes measured domain-specific aspects of self-esteem, self-compassion, quality of life, depression and anxiety. The treatment group showed significantly higher levels of self-rated self-esteem compared to the control group at post-treatment, with a large between-group effect-size (RSES, d = 1.18). Further, the treatment had significant positive impact on secondary measures of self-esteem, self-compassion, quality of life, depression and anxiety. The results of this pilot-RCT suggest that ICBT can be effective for treating low self-esteem in adolescents, decrease depression and anxiety levels, and increasing quality of life. Replication of the results in larger samples is needed.    

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  • 12.
    Berg, Matilda
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Rozental, Alexander
    Karolinska Inst, Sweden; UCL, England.
    de Brun Mangs, Josefine
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Näsman, Maja
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Strömberg, Karin
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Viberg, Linn
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Wallner, Erik
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Åhman, Hanna
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Silfvernagel, Kristin
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Zetterqvist, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Topooco, Naira
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Ctr M2Hlth, CA USA.
    Johansson Capusan, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. UCL, England.
    The Role of Learning Support and Chat-Sessions in Guided Internet-Based Cognitive Behavioral Therapy for Adolescents With Anxiety: A Factorial Design Study2020In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 11, article id 503Article in journal (Refereed)
    Abstract [en]

    Background Increased awareness of anxiety in adolescents emphasises the need for effective interventions. Internet-based cognitive behavioural therapy (ICBT) could be a resource-effective and evidence-based treatment option, but little is known about how to optimize ICBT or which factors boost outcomes. Recently, the role of knowledge in psychotherapy has received increased focus. Further, chat-sessions are of interest when trying to optimize ICBT for youths. This study aimed to evaluate the role of learning support and chat-sessions during ICBT for adolescent anxiety, using a factorial design. Method A total of 120 adolescents were randomised to one of four treatment groups, in a 2x2 design with two factors: with or without learning support and/or chat-sessions. Results Anxiety and depressive symptoms were reduced (Beck Anxiety Inventory- BAI; Cohensd=0.72; Beck Depression Inventory- BDI;d=0.97). There was a main effect of learning support on BAI (d=0.38), and learning support increased knowledge gain (d =0.42). There were no main effects or interactions related to the chat-sessions. Treatment effects were maintained at 6-months, but the added effect of learning support had by then vanished. Conclusion ICBT can be an effective alternative when treating adolescents with anxiety. Learning support could be of importance to enhance short-term treatment effects, and should be investigated further.

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  • 13.
    Bergman, David
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Hagström, Hannes
    Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Johansson Capusan, Andrea
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Mårild, Karl
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden; Department of Pediatric Gastroenterology, Queen Silvia Children’s Hospital, Gothenburg, Sweden.
    Nyberg, Fredrik
    School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sundquist, Kristina
    Center for Primary Health Care Research, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Ludvigsson, Jonas F
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Orebro University Hospital, Orebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
    Incidence of ICD-Based Diagnoses of Alcohol-Related Disorders and Diseases from Swedish Nationwide Registers and Suggestions for Coding2020In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 12, p. 1433-1442Article in journal (Refereed)
    Abstract [en]

    Aim: To improve consistency between register studies in Sweden and ensure valid comparisons of possible changes in alcohol-related disorders and diseases (ARDDs) over time, we propose a definition of ARDDs. Based on this definition, we examined Sweden's incidence rates of ARDDs from 1970 to 2018 in non-primary healthcare settings (inpatient and outpatient).

    Methods: Swedish Society of Epidemiology members were invited to give feedback on the International Classification of Disease (ICD) codes with a potential link to alcohol use. We then calculated age-standardised and age-specific incidence of ARDDs over time according to the National Patient Register, and the lifetime prevalence of ARDDs diagnosed in adults alive in Sweden on Dec 31, 2018.

    Results: Sweden's estimated incidence of ARDDs increased substantially after introducing the new ICD-9 codes in 1987. In the past 10 years (2009-2018), the incidence of ARDDs has been stable (males: 110/100,000 person-years, females: 49/100,000 person-years). Requiring at least two ICD records for diagnosed ARDDs led to a somewhat lower incidence of ARDDs (males: 71 per 100,000 person-years, females: 29 per 100,000 person-years). In Sweden, the lifetime prevalence of diagnosed ARDDs in adults on Dec 31, 2018, was 1.9% (95% CI=1.9-1.9).

    Conclusion: In this nationwide study, we found an incidence of ARDDs of 50-100/100,000 person-years. In 2018, 1 in 52 adults in Sweden had been diagnosed with ARDDs in the National Patient Register.

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  • 14.
    Best, Laura M.
    et al.
    Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada.
    Williams, Belinda
    Ctr Addict & Mental Hlth, Canada.
    Le Foll, Bernard
    Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Univ Toronto, Canada.
    Mansouri, Esmaeil
    Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada.
    Bazinet, Richard P.
    Univ Toronto, Canada.
    Lin, Lin
    Univ Toronto, Canada.
    De Luca, Vincenzo
    Univ Toronto, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Ctr Addict & Mental Hlth, Canada.
    Lagzdins, Dina
    Ctr Addict & Mental Hlth, Canada.
    Rusjan, Pablo
    Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada.
    Tyndale, Rachel F.
    Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Univ Toronto, Canada.
    Wilson, Alan A.
    Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada.
    Hendershot, Christian S.
    Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Ctr Addict & Mental Hlth, Canada.
    Heilig, Markus
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Houle, Sylvain
    Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada.
    Tong, Junchao
    Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada.
    Kish, Stephen J.
    Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Ctr Addict & Mental Hlth, Canada.
    Boileau, Isabelle
    Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Ctr Addict & Mental Hlth, Canada.
    Lower brain fatty acid amide hydrolase in treatment-seeking patients with alcohol use disorder: a positron emission tomography study with [C-11]CURB2020In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 45, no 8, p. 1289-1296Article in journal (Refereed)
    Abstract [en]

    The endocannabinoid enzyme, fatty acid amide hydrolase (FAAH), has been proposed as a therapeutic target for alcohol use disorder (AUD) and co-morbid psychiatric illnesses. Investigating this target in the living human brain and its relationship to clinical outcome is a critical step of informed drug development. Our objective was to establish whether brain FAAH levels are low in individuals with AUD and related to drinking behavior. In this pilot study, treatment-seeking patients with AUD completed two PET scans with the FAAH radiotracer [C-11]CURB after 3-7 days (n = 14) and 2-4 weeks (n = 9) of monitored abstinence. Healthy controls (n = 25) completed one scan. FAAH genetic polymorphism (rs324420) and blood concentrations of anandamide and other N-acylethanolamines metabolized by FAAH were determined and AUD symptoms assessed. In AUD, brain FAAH levels were globally lower than controls during early abstinence (F(1,36) = 5.447; p = 0.025)) and FAAH substrates (anandamide, oleoylethanolamide, and N-docosahexaenoylethanolamide) were significantly elevated (30-67%). No significant differences in FAAH or FAAH substrates were noted after 2-4 weeks abstinence. FAAH levels negatively correlated with drinks per week (r = -0.57, p = 0.032) and plasma concentrations of the three FAAH substrates (r > 0.57; p < 0.04)). Our findings suggest that early abstinence from alcohol in AUD is associated with transiently low brain FAAH levels, which are inversely related to heavier alcohol use and elevated plasma levels of FAAH substrates. Whether low FAAH is an adaptive beneficial response to chronic alcohol is unknown. Therapeutic strategies focusing on FAAH inhibition should consider the possibility that low FAAH during early abstinence may be related to drinking.

  • 15.
    Blanken, M. A. J. T.
    et al.
    Vrije Univ, Netherlands; Vrije Univ Amsterdam Med Ctr, Netherlands.
    Oudega, M. L.
    GGZ InGeest Specialized Mental Hlth Care, Netherlands; Vrije Univ, Netherlands; Vrije Univ, Netherlands; Vrije Univ Amsterdam Med Ctr, Netherlands.
    Hoogendoorn, A. W.
    GGZ InGeest Specialized Mental Hlth Care, Netherlands; Vrije Univ, Netherlands; Vrije Univ Amsterdam Med Ctr, Netherlands.
    Sonnenberg, C. S.
    Vrije Univ, Netherlands; GGZ Parnassia NH, Netherlands.
    Rhebergen, D.
    Vrije Univ, Netherlands; Vrije Univ Amsterdam Med Ctr, Netherlands; GGZ Cent, Netherlands.
    Klumpers, U. M. H.
    Vrije Univ, Netherlands; Vrije Univ, Netherlands; Vrije Univ Amsterdam Med Ctr, Netherlands.
    Van Diermen, L.
    Psychiat Ctr Bethanie, Belgium; Univ Antwerp, Belgium; Univ Psychiat Ctr UPC Duffel, Belgium.
    Birkenhager, T.
    Univ Antwerp, Belgium; Erasmus MC, Netherlands.
    Schrijvers, D.
    Univ Antwerp, Belgium; Univ Psychiat Ctr UPC Duffel, Belgium.
    Redlich, R.
    Univ Halle, Germany; Univ Munster, Germany.
    Dannlowski, U.
    Univ Munster, Germany.
    Heindel, W.
    Univ Munster, Germany.
    Coenjaerts, M.
    Univ Hosp Bonn, Germany.
    Nordanskog, Pia
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Oltedal, L.
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Kessler, U.
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Frid, L. M.
    Univ Bergen, Norway.
    Takamiya, A.
    Keio Univ, Japan; Katholieke Univ Leuven, Belgium.
    Kishimoto, T.
    Keio Univ, Japan.
    Jorgensen, M. B.
    Univ Copenhagen, Denmark; Univ Copenhagen, Denmark.
    Jorgensen, A.
    Univ Copenhagen, Denmark; Univ Copenhagen, Denmark.
    Bolwig, T.
    Univ Copenhagen, Denmark.
    Emsell, L.
    Katholieke Univ Leuven, Belgium.
    Sienaert, P.
    Katholieke Univ Leuven, Belgium.
    Bouckaert, F.
    Katholieke Univ Leuven, Belgium.
    Abbott, C. C.
    Univ New Mexico, NM 87131 USA.
    Peran, P.
    Univ Toulouse, France.
    Arbus, C.
    Univ Toulouse, France.
    Yrondi, A.
    Univ Toulouse, France.
    Kiebs, M.
    Univ Bonn, Germany; Univ Hosp Oldenburg, Germany.
    Philipsen, A.
    Univ Bonn, Germany.
    van Waarde, J. A.
    Rijnstate Arnhem, Netherlands.
    Prinsen, E.
    Rijnstate Arnhem, Netherlands.
    van Verseveld, M.
    Rijnstate Arnhem, Netherlands.
    Van Wingen, G.
    Univ Amsterdam, Netherlands; Amsterdam Neurosci, Netherlands.
    ten Doesschate, F.
    Rijnstate Arnhem, Netherlands; Univ Amsterdam, Netherlands.
    Camprodon, J. A.
    Harvard Med Sch, MA USA.
    Kritzer, M.
    Harvard Med Sch, MA USA.
    Barbour, T.
    Massachusetts Gen Hosp, MA 02114 USA.
    Argyelan, M.
    Feinstein Inst Med Res, NY USA.
    Cardoner, N.
    Hosp Santa Creu & Sant Pau, Spain; Univ Autonoma Barcelona, Spain; Carlos III Hlth Inst, Spain.
    Urretavizcaya, M.
    Carlos III Hlth Inst, Spain; Bellvitge Univ Hosp, Spain; Univ Barcelona, Spain.
    Soriano-Mas, C.
    Carlos III Hlth Inst, Spain; Bellvitge Univ Hosp, Spain; Univ Barcelona, Spain.
    Narr, K. L.
    Univ Calif Los Angeles, CA USA.
    Espinoza, R. T.
    Univ Calif Los Angeles, CA USA.
    Prudic, J.
    Columbia Univ, NY 10027 USA.
    Rowny, S.
    Columbia Univ, NY 10027 USA.
    van Eijndhoven, Ph.
    Radboud Univ Nijmegen, Netherlands.
    Tendolkar, I.
    Radboud Univ Nijmegen, Netherlands.
    Dols, A.
    Vrije Univ, Netherlands; Vrije Univ Amsterdam Med Ctr, Netherlands; Univ Med Ctr Utrecht, Netherlands.
    Sex-specifics of ECT outcome2023In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 326, p. 243-248Article in journal (Refereed)
    Abstract [en]

    Objective: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. Methods: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). Results: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. Conclusion: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex-specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

  • 16.
    Blomberg, Rina
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Johansson Capusan, Andrea
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Signoret, Carine
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Danielsson, Henrik
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Rönnberg, Jerker
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    The Effects of Working Memory Load on Auditory Distraction in Adults With Attention Deficit Hyperactivity Disorder2021In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 15, article id 771711Article in journal (Refereed)
    Abstract [en]

    Cognitive control provides us with the ability to inter alia, regulate the locus of attention and ignore environmental distractions in accordance with our goals. Auditory distraction is a frequently cited symptom in adults with attention deficit hyperactivity disorder (aADHD)-yet few task-based fMRI studies have explored whether deficits in cognitive control (associated with the disorder) impedes on the ability to suppress/compensate for exogenously evoked cortical responses to noise in this population. In the current study, we explored the effects of auditory distraction as function of working memory (WM) load. Participants completed two tasks: an auditory target detection (ATD) task in which the goal was to actively detect salient oddball tones amidst a stream of standard tones in noise, and a visual n-back task consisting of 0-, 1-, and 2-back WM conditions whilst concurrently ignoring the same tonal signal from the ATD task. Results indicated that our sample of young aADHD (n = 17), compared to typically developed controls (n = 17), had difficulty attenuating auditory cortical responses to the task-irrelevant sound when WM demands were high (2-back). Heightened auditory activity to task-irrelevant sound was associated with both poorer WM performance and symptomatic inattentiveness. In the ATD task, we observed a significant increase in functional communications between auditory and salience networks in aADHD. Because performance outcomes were on par with controls for this task, we suggest that this increased functional connectivity in aADHD was likely an adaptive mechanism for suboptimal listening conditions. Taken together, our results indicate that aADHD are more susceptible to noise interference when they are engaged in a primary task. The ability to cope with auditory distraction appears to be related to the WM demands of the task and thus the capacity to deploy cognitive control.

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  • 17.
    Blomberg, Rina
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research Division. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Signoret, Carine
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research Division. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Danielsson, Henrik
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research Division. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Perini, Irene
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Rönnberg, Jerker
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research Division. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Johansson Capusan, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Aberrant resting-state connectivity of auditory, ventral attention/salience and default-mode networks in adults with attention deficit hyperactivity disorder2022In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 16, article id 972730.Article in journal (Refereed)
    Abstract [en]

    Background Numerous resting-state studies on attention deficit hyperactivity disorder (ADHD) have reported aberrant functional connectivity (FC) between the default-mode network (DMN) and the ventral attention/salience network (VA/SN). This finding has commonly been interpreted as an index of poorer DMN regulation associated with symptoms of mind wandering in ADHD literature. However, a competing perspective suggests that dysfunctional organization of the DMN and VA/SN may additionally index increased sensitivity to the external environment. The goal of the current study was to test this latter perspective in relation to auditory distraction by investigating whether ADHD-adults exhibit aberrant FC between DMN, VA/SN, and auditory networks. Methods Twelve minutes of resting-state fMRI data was collected from two adult groups: ADHD (n = 17) and controls (n = 17); from which the FC between predefined regions comprising the DMN, VA/SN, and auditory networks were analyzed. Results A weaker anticorrelation between the VA/SN and DMN was observed in ADHD. DMN and VA/SN hubs also exhibited aberrant FC with the auditory network in ADHD. Additionally, participants who displayed a stronger anticorrelation between the VA/SN and auditory network at rest, also performed better on a cognitively demanding behavioral task that involved ignoring a distracting auditory stimulus. Conclusion Results are consistent with the hypothesis that auditory distraction in ADHD is linked to aberrant interactions between DMN, VA/SN, and auditory systems. Our findings support models that implicate dysfunctional organization of the DMN and VA/SN in the disorder and encourage more research into sensory interactions with these major networks.

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  • 18.
    Boström, Anita
    et al.
    Institutionen för hälsovetenskaper, Karlstads universitet, Sverige.
    Lindmark, Ulrika
    Jönköping University, HHJ, Avd. för naturvetenskap och biomedicin, Sverige.
    Ludvigsson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine.
    Saveman, Britt-Inger
    Institutionen för omvårdnad, Umeå universitet, Sverige.
    Simmons, Johanna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Siverskog, Anna
    Jönköping University, HHJ, Avd. för socialt arbete, Sverige.
    Åkerlund, Nina
    Jönköping University, HHJ, Avd. för socialt arbete, Sverige.
    Förekomsten av våld i nära relationer bland äldre personer2022In: Äldre personers utsatthet för våld i nära relationer: Interprofessionella perspektiv / [ed] Lena Östlund, Lund: Studentlitteratur AB , 2022, p. 31-64Chapter in book (Other academic)
  • 19.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Hoffmann, Mikael
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Comment on Hauser et al.: Medical use of opioids in Europe - Methodological concerns about data from the International Narcotics Control Board2022In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 26, no 4, p. 937-938Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 20.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Hoffmann, Mikael
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Opioid availability statistics from the International Narcotics Control Board do not reflect the medical use of opioids: comparison with sales data from Scandinavia2021In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 21, no 4, p. 696-706Article in journal (Refereed)
    Abstract [en]

    Objectives: Opioid analgesics are essential in clinical practice, but their excessive use is associated with addiction risk. Increases in opioid prescription rates have fuelled an epidemic of opioid addiction in the USA, making statistics on medical opioid use a critical warning signal. A dramatic 150% increase in Swedish opioid access 2001-2013 was recently reported based on data from the International Narcotics Control Board (INCB; Berterame et al. 2016) in conflict with other studies of opioid use in the Nordic countries. This article aims to analyse to what degree published INCB statistics on opioids in Scandinavia (Denmark, Norway and Sweden) reflect actual medical use and study the methodological reasons for putative discrepancies. Methods: Data on aggregated total national sales of opioids for the whole population, including hospitals, were collected from the Swedish e-Health Authority. Total sales data for Denmark and drugs dispensed at pharmacies in Norway are publicly available through the relevant authorities websites. Results: INCB opioid statistics during the period 2001-2013 were markedly inconsistent with sales data from Scandinavia, calling the reliability of INCB data into question. INCB-data were flawed by (a) over-representing the volume of fentanyl, (b) under-reporting of codeine, and (c) by not including tramadol. Conclusions: Opioid availability, as expressed by INCB statistics, does not reflect medical opioid use. It is crucial to underline that INCB statistics are based on the manual compilation of national production, import and export data from manufacturers and drug companies. This is not the same amount that is prescribed and consumed within the health care system. Moreover, there are methodological problems in the INCB reports, in particular concerning fentanyl, codeine and tramadol. We suggest that INCB should carefully review the quality of their data on medical opioids.

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  • 21.
    Böhme, Rebecca
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Frost-Karlsson, Morgan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Johansson Capusan, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Sharpened self-other distinction in attention deficit hyperactivity disorder2020In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 27, article id 102317Article in journal (Refereed)
    Abstract [en]

    Introduction

    Differentiation between self-produced tactile stimuli and touch by others is necessary for social interactions and for a coherent concept of “self”. In attention-deficit-hyperactivity-disorder (ADHD), tactile hypersensitivity and social cognition problems are part of the symptomatology, but pathophysiological mechanisms are largely unknown. Differentiation of self- and non-self- generated sensations might be key to understand and develop novel strategies for managing hypersensitivity. Here, we compared the neural signatures of affective self- and other-touch between adults with ADHD and neurotypical controls (NC).

    Methods

    Twenty-eight adult ADHD participants and 30 age- and gender-matched NC performed a self-other-touch-task during functional magnetic resonance imaging: they stroked their own arm, an object, or were stroked by the experimenter. In addition, tactile detection thresholds and rubber hand illusion (RHI) were measured.

    Results

    ADHD participants had more autistic traits than NC and reported to engage less in interpersonal touch. They also reported to be more sensitive to tactile stimuli. Compared to NC, ADHD participants showed enhanced responses to both the self- and other-touch conditions: stronger deactivation during self-touch in the anterior and posterior insula, and increased activation during other-touch in primary somatosensory cortex. ADHD participants had intact tactile detection thresholds, but were less susceptible to the RHI.

    Conclusions

    Unaltered detection thresholds suggest that peripheral processing is intact, and that hypersensitivity might be driven by central mechanisms. This has clinical implications for managing somatosensory hypersensitivity in ADHD. The more pronounced differentiation between self- and other-touch might indicate a clearer self-other-distinction. This is of interest regarding body ownership perception in both NC and ADHD, and possibly other psychiatric conditions with altered self-experiences, like schizophrenia. A sharper boundary of the own body might relate to deficits in social cognition and tactile hypersensitivity.

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  • 22.
    de Wit, Harriet
    et al.
    Univ Chicago, IL 60637 USA.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bershad, A. K.
    Univ Calif Los Angeles, CA USA.
    Does acute stress play a role in the lasting therapeutic effects of psychedelic drugs?2023In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 48, no 10, p. 1422-1424Article in journal (Refereed)
    Abstract [en]

    Psychedelic drugs, when used in the context of psychotherapy, can produce significant and long-lasting memories with enduring beneficial effects. Yet, the behavioral and neurobiological mechanisms that underlie these beneficial effects remain a mystery. Here, we suggest that both the quality and durability of memories of the drug-facilitated therapeutic experience may be mediated, in part, by the acute stress responses induced by the drugs. It is known that high doses of psychedelic drugs activate autonomic and hormonal stress responses. For evolutionarily adaptive reasons, acute stress is known to i) instill meaning to the immediate context in which it is experienced, and ii) lead to the formation of salient and lasting memories of the events surrounding the stress. Thus, the stress-inducing effect of psychedelic drugs may contribute to the reported sense of meaning, as well as the durability of the memory of the drug experience. When used in a therapeutic context these actions may i) enhance the salience of insights gained during the experience and ii) strengthen the memories formed by these experiences. Future empirical studies will help to determine whether acute stress contributes to the emotional significance and lasting effects of psychedelic-assisted psychotherapy.

  • 23.
    Domi, Esi
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Domi, Ana
    Univ Gothenburg, Sweden.
    Adermark, Louise
    Univ Gothenburg, Sweden.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Augier, Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Neurobiology of alcohol seeking behavior2021In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 157, no 5, p. 1585-1614Article, review/survey (Refereed)
    Abstract [en]

    Alcohol addiction is a chronic relapsing brain disease characterized by an impaired ability to stop or control alcohol use despite adverse consequences. A main challenge of addiction treatment is to prevent relapse, which occurs in more than >50% of newly abstinent patients with alcohol disorder within 3 months. In people suffering from alcohol addiction, stressful events, drug-associated cues and contexts, or re-exposure to a small amount of alcohol trigger a chain of behaviors that frequently culminates in relapse. In this review, we first present the preclinical models that were developed for the study of alcohol seeking behavior, namely the reinstatement model of alcohol relapse and compulsive alcohol seeking under a chained schedule of reinforcement. We then provide an overview of the neurobiological findings obtained using these animal models, focusing on the role of opioids systems, corticotropin-release hormone and neurokinins, followed by dopaminergic, glutamatergic, and GABAergic neurotransmissions in alcohol seeking behavior.

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  • 24.
    Domi, Esi
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Xu, Li
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Sichuan Prov Peoples Hosp, Peoples R China.
    Paetz, Marvin
    Heidelberg Univ, Germany.
    Nordeman, Anton
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Gaëlle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Holm, Lovisa
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Toivainen, Sanne
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Hansson, Anita C.
    Heidelberg Univ, Germany.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Nicotine increases alcohol self-administration in male rats via a mu-opioid mechanism within the mesolimbic pathway2020In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 177, no 19, p. 4516-4531Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: Alcohol and nicotine use disorders are commonly comorbid. Both alcohol and nicotine can activate opioid systems in reward-related brain regions, leading to adaptive changes in opioid signalling upon chronic exposure. The potential role of these adaptations for comorbidity is presently unknown. Here, we examined the contribution of mu and kappa-opioid receptors to nicotine-induced escalation of alcohol self-administration in rats. Experimental Approach: Chronic nicotine was tested on alcohol self-administration and motivation to obtain alcohol. We then tested the effect of the kappa antagonist CERC-501 and the preferential mu receptor antagonist naltrexone on basal and nicotine-escalated alcohol self-administration. To probe mu or kappa receptor adaptations, receptor binding and G-protein coupling assays were performed in reward-related brain regions. Finally, dopaminergic activity in response to alcohol was examined, using phosphorylation of DARPP-32 in nucleus accumbens as a biomarker. Key Results: Nicotine robustly induced escalation of alcohol self-administration and motivation to obtain alcohol. This was blocked by naltrexone but not by CERC-501. Escalation of alcohol self-administration was associated with decreased DAMGO-stimulated mu receptor signalling in the ventral tegmental area (VTA) and decreased pDARPP-32 in the nucleus accumbens shell in response to alcohol. Conclusions and Implications: Collectively, these results suggest that nicotine contributes to escalate alcohol self-administration through a dysregulation of mu receptor activity in the VTA. These data imply that targeting mu rather than kappa receptors may be the preferred pharmacotherapeutic approach for the treatment of alcohol use disorder when nicotine use contributes to alcohol consumption.

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  • 25.
    Domi, Esi
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Camerino, Italy.
    Xu, Li
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Toivainen Eloff, Sanne
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Wiskerke, Joost
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Coppola, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Holm, Lovisa
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Petrella, Michele
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Activation of GABA(B) receptors in central amygdala attenuates activity of PKC delta plus neurons and suppresses punishment-resistant alcohol self-administration in rats2023In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 48, p. 1386-1395Article in journal (Refereed)
    Abstract [en]

    Alcohol use despite negative consequences is a core phenomenon of alcohol addiction. We recently used alcohol self-administration that is resistant to footshock punishment as a model of this behavior, and found that activity of PKC delta + GABAergic neurons in the central amygdala (CeA) is a determinant of individual susceptibility for punishment resistance. In the present study, we examined whether activation of GABA(B) receptors in CeA can attenuate the activity of PKC delta + neurons in this region, and whether this will result in suppression of punishment- resistant alcohol self-administration in the minority of rats that show this behavior. Systemic administration of the clinically approved GABA(B) agonist baclofen (1 and 3 mg/kg) dose- dependently reduced punishment-resistant alcohol self-administration. Bilateral microinjections of baclofen into CeA (64 ng in 0.3 mu l/side) reduced the activity of PKC delta + neurons, as measured by Fos expression. This manipulation also selectively suppressed punished alcohol self-administration in punishment-resistant rats. Expression analysis indicated that virtually all CeA PKC delta + neurons express the GABA(B) receptor. Using in vitro electrophysiology, we found that baclofen induced hyperpolarization of CeA neurons, reducing their firing rate in response to depolarizing current injections. Together, our findings provide a potential mechanism that contributes to the clinical efficacy of baclofen in alcohol addiction. Therapeutic use of baclofen itself is limited by problems of tolerance and need for dose escalation. Our findings support a mechanistic rationale for developing novel, improved alcohol addiction medications that target GABA(B) receptors, and that lack these limitations, such as e.g., GABA(B) positive allosteric modulators (PAM:s).

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  • 26.
    Domi, Esi
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Xu, Li
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Elect Sci & Technol China, Peoples R China.
    Toivainen, Sanne
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Nordeman, Anton
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Gobbo, Francesco
    Univ Edinburgh, Scotland.
    Venniro, Marco
    Univ Maryland, MD 21201 USA.
    Shaham, Yavin
    Natl Inst Drug Abuse NIDA, MD 21224 USA.
    Messing, Robert O.
    Univ Texas Austin, TX 78712 USA; Univ Texas Austin, TX 78712 USA; Univ Texas Austin, TX 78712 USA.
    Visser, Esther
    Vrije Univ Amsterdam, Netherlands.
    van den Oever, Michel C.
    Vrije Univ Amsterdam, Netherlands.
    Holm, Lovisa
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Barbier, Estelle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    A neural substrate of compulsive alcohol use2021In: Science Advances, E-ISSN 2375-2548, Vol. 7, no 34, article id eabg9045Article in journal (Refereed)
    Abstract [en]

    Alcohol intake remains controlled in a majority of users but becomes "compulsive," i.e., continues despite adverse consequences, in a minority who develop alcohol addiction. Here, using a footshock-punished alcohol self-administration procedure, we screened a large population of outbred rats to identify those showing compulsivity operationalized as punishment-resistant self-administration. Using unsupervised clustering, we found that this behavior emerged as a stable trait in a subpopulation of rats and was associated with activity of a brain network that included central nucleus of the amygdala (CeA). Activity of PKC delta(+) inhibitory neurons in the lateral subdivision of CeA (CeL) accounted for similar to 75% of variance in punishment-resistant alcohol taking. Activity-dependent tagging, followed by chemogenetic inhibition of neurons activated during punishment-resistant self-administration, suppressed alcohol taking, as did a virally mediated shRNA knockdown of PKC delta in CeA. These findings identify a previously unknown mechanism for a core element of alcohol addiction and point to a novel candidate therapeutic target.

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  • 27.
    Donevan, Meghan
    et al.
    Ersta Skondal Bracke Univ Coll, Sweden.
    Jonsson, Linda
    Ersta Skondal Bracke Univ Coll, Sweden.
    Bladh, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Priebe, Gisela
    Lund Univ, Sweden.
    Fredlund, Cecilia
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Svedin, Carl Goran
    Ersta Skondal Bracke Univ Coll, Sweden.
    Adolescents Use of Pornography: Trends over a Ten-year Period in Sweden2022In: Archives of Sexual Behavior, ISSN 0004-0002, E-ISSN 1573-2800, Vol. 51, no 2, p. 1125-1140Article in journal (Refereed)
    Abstract [en]

    Using survey data from three nationally representative surveys in 2004, 2009, and 2014 among senior high school students in Sweden, this study investigates trends in adolescents lifetime prevalence of pornography use, frequency of pornography use, and type of pornography used over time. While almost all boys and a considerable proportion of girls used pornography across the three waves, the lifetime prevalence of pornography use decreased overall for both girls and boys. The share of boys who use pornography frequently increased over the three survey cycles; those who reported using pornography daily increased from 11% in 2004 to 24% in 2014. In contrast, there was no change in girls who reported using pornography daily, while the proportion who never used pornography increased from 40% in 2004 to 51% in 2014. Adolescents appear to use a narrower range of different pornography types over the survey cycles. Multiple logistic regression models were generated to investigate factors associated with pornography use over the 10-year period. The results suggest that rule-breaking behavior, having higher economic status and higher academic achievement were related to boys pornography use, while rule-breaking behavior, early sexual debut and victimization were associated with girls pornography use.

  • 28.
    Ekstrand, Joakim
    et al.
    Lund Univ, Sweden.
    Fattah, Christian
    Lund Univ, Sweden.
    Persson, Marcus
    Lund Univ, Sweden.
    Cheng, Tony
    Lund Univ, Sweden.
    Nordanskog, Pia
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience.
    Åkeson, Jonas
    Lund Univ, Sweden.
    Tingström, Anders
    Lund Univ, Sweden.
    Lindström, Mats B.
    Lund Univ, Sweden.
    Nordenskjöld, Axel
    Örebro Univ, Sweden.
    Rad, Pouya Movahed
    Lund Univ, Sweden.
    Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT)2022In: International Journal of Neuropsychopharmacology, ISSN 1461-1457, E-ISSN 1469-5111, Vol. 25, no 5, p. 339-349Article in journal (Refereed)
    Abstract [en]

    Background Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared with electroconvulsive therapy (ECT), the most effective therapy for depression. Methods Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery angstrom sberg Depression Rating Scale score <= 10). Secondary outcomes included adverse events (AEs), time to remission, and relapse. Treatment sessions (maximum of 12) were administered until remission or maximal effect was achieved. Remitters were followed for 12 months after the final treatment session. Results In total 186 inpatients were included and received treatment. Among patients receiving ECT, 63% remitted compared with 46% receiving ketamine infusions (P = .026; difference 95% CI 2%, 30%). Both ketamine and ECT required a median of 6 treatment sessions to induce remission. Distinct AEs were associated with each treatment. Serious and long-lasting AEs, including cases of persisting amnesia, were more common with ECT, while treatment-emergent AEs led to more dropouts in the ketamine group. Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within 12 months in the ketamine and ECT groups, respectively (P = .52). Conclusion Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18-85 years) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.

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  • 29.
    Fredlund, Cecilia
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Jonsson, Linda S.
    Marie Cederschiold Univ, Sweden.
    Perceived Help and Support for Sex as Self-Injury: A Qualitative Study of a Swedish Sample2023In: Archives of Sexual Behavior, ISSN 0004-0002, E-ISSN 1573-2800, Vol. 52, no 1, p. 149-160Article in journal (Refereed)
    Abstract [en]

    Earlier research has found that sexual acts could be used as a means of self-injury, with comparable functions to nonsuicidal self-injury (NSSI) such as cutting or burning the skin. However, no previous study has investigated the experience of help and support in relation to sex as a means of self-injury (SASI), which this study aims to investigate. The study was based on an anonymous open-ended questionnaire published from December 2016 to April 2017 on the websites of NGOs working with help and support for women and youths in Sweden. In total, 197 participants (mostly women, mean age 27.9 years, range 15-64 years) with self-reported experiences of SASI were included in the study. Three main themes were found concerning experiences of help and support for SASI. The need for: (1) Framing the behavior of SASI, to find a word for SASI-to know it exists, to get questions and information about SASI and its function; (2) Flexible, respectful, and professional help and support from an early age, to be listened to and confirmed in ones experience of SASI; and (3) Help with underlying reasons to exit SASI such as finding ones own value and boundaries through conventional therapy, through life itself, or through therapy for underlying issues such as earlier traumatic events, PTSD, dissociation, or anxiety. In conclusion, similar interventions could be helpful for SASI as for NSSI, irrespective of the topographical differences between the behaviors, but the risk of victimization and traumatization must also be addressed in SASI.

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  • 30.
    Frost-Karlsson, Morgan
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Johansson Capusan, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Perini, Irene
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Zetterqvist, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Gustafsson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Böhme, Rebecca
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Neural processing of self-touch and other-touch in anorexia nervosa and autism spectrum condition2022In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 36, article id 103264Article in journal (Refereed)
    Abstract [en]

    Introduction: The tactile sense plays a crucial role in the development and maintenance of a functional bodily self. The ability to differentiate between self-and nonself-generated touch contributes to the perception of the bodies boundaries and more generally to self-other-distinction, both of which are thought be altered in anorexia nervosa (AN) and autism spectrum condition (AS). While it has been suggested that AN and AS are characterized by overlapping symptomatology, they might differ regarding body perception and self-other-distinction. Methods: Participants with a diagnosis of AN (n = 25), AS (n = 29), and a comparison group without diagnoses (n = 57) performed a self-other-touch task during functional brain imaging. In the experimental conditions, they stroked their own arm or were stroked on the arm by an experimenter. Results: As shown previously, the CG group showed lower activation or deactivation in response to self-touch compared to social touch from someone else. A main group effect was found in areas including somatosensory cortex, frontal and temporal gyri, insula, and subcortical regions. This was driven by increased activations in participants with AN, while participants in the AS group showed mostly comparable activations to the com-parison group. Conclusions: AN diagnosis was associated with an increased neural activity in response to both self-touch and social touch. Failure to attenuate self-touch might relate to altered predictions regarding the own body and reduced perception of bodily boundaries. Participants with an AS diagnosis were mostly comparable to the comparison group, potentially indicating unaltered tactile self-other-distinction.

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  • 31.
    Glans, Martin R.
    et al.
    Orebro Univ, Sweden.
    Thelin, Nils
    Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Humble, Mats B.
    Orebro Univ, Sweden.
    Elwin, Marie
    Orebro Univ, Sweden.
    Bejerot, Susanne
    Orebro Univ, Sweden; Orebro Univ, Sweden; Karolinska Inst KI, Sweden.
    The Relationship Between Generalised Joint Hypermobility and Autism Spectrum Disorder in Adults: A Large, Cross-Sectional, Case Control Comparison2022In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 12, article id 803334Article in journal (Refereed)
    Abstract [en]

    Autism spectrum disorder (ASD) and generalised joint hypermobility (GJH) share a number of clinical manifestations including proprioceptive impairment, motor difficulties, sensory hypersensitivity, and autonomic dysfunction. Clinical observations suggest that GJH is overrepresented in ASD. However, there are currently few systematic studies available. Knowledge about comorbidities may unfold common aetiopathological pathways underlying the association and improve the clinical management. The aim of this large, cross-sectional comparative study is to evaluate the relationship between ASD and GJH in adults. Data on joint hypermobility, symptoms associated with both hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS), lifetime psychiatric diagnoses, psychiatric rating scales for ASD and attention deficit hyperactivity disorder (ADHD), and socio-demographics was collected for 199 individuals with ASD and 419 non-ASD community controls. Logistic regression models adjusting for covariates (age, sex, ethnicity) revealed a significant relationship between ASD and GJH and between ASD and symptomatic GJH, with adjusted odds ratios of 3.1 (95% CI: 1.9, 5.2; p < 0.001) and 4.9 (95% CI: 2.6, 9.0; p < 0.001), respectively. However, the high prevalence of comorbid ADHD in the study sample reduces the generalizability of the results among individuals with ASD without comorbid ADHD. Possibly, an additional ADHD phenotype is the primary driver of the association between ASD and GJH. Furthermore, GJH with additional self-reported symptoms, suggestive of HSD/hEDS, showed a stronger association with ASD than did non-specified GJH, indicating that symptomatic GJH plays a greater role in the relationship than non-specified GJH does. Therefore, the current study underscores the need of careful sample subclassifications. ASD with GJH may represent a novel subgroup of ASD in terms of aetiopathology and clinical presentation. Future research should elucidate the aetiological factors behind the association between ASD and GJH and evaluate how the comorbidity of GJH affects ASD outcomes.

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  • 32.
    Glans, Martin
    et al.
    Orebro Univ, Sweden.
    Thelin, Nils
    Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Humble, Mats B.
    Orebro Univ, Sweden; Orebro Univ, Sweden.
    Elwin, Marie
    Orebro Univ, Sweden.
    Bejerot, Susanne
    Orebro Univ, Sweden; Orebro Univ, Sweden; Karolinska Inst, Sweden.
    Association between adult attention-deficit hyperactivity disorder and generalised joint hypermobility: A cross-sectional case control comparison2021In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 143, p. 334-340Article in journal (Refereed)
    Abstract [en]

    Growing evidence suggests an unexpected association between generalised joint hypermobility (GJH) and several psychiatric conditions, and a shared pathophysiology has been proposed. No previous studies on adult attention-deficit/hyperactivity disorder (ADHD) are available. This study aimed to evaluate the association between adult ADHD and GJH. A total of 431 adults with ADHD and 417 non-ADHD controls were included in this cross-sectional comparative study. GJH was assessed by physical examination following the Beighton scoring system (BSS). Furthermore, musculoskeletal symptoms and skin abnormalities were queried to create a proxy for symptomatic GJH (e.g., Hypermobility spectrum disorders and Ehlers-Danlos syndrome) to differentiate this from non-specified GJH defined by BSS only. Logistic regression examined the influence of ADHD and candidate covariates (age, sex, ethnicity) on GJH and symptomatic GJH, respectively. ADHD was significantly associated with GJH, as defined by the BSS, with adjusted odds ratios of 4.7 (95% confidence interval [CI] 3.0-7.2, p &lt; .005). Likewise, ADHD was significantly associated with symptomatic GJH, as defined by the BSS and additional symptoms, with adjusted odds ratios of 6.9 (CI 95% 4.1-11.9, p &lt; .005). Our results suggest that GJH may represent a marker for an underlying systemic disorder involving both connective tissue and the central nervous system. GJH with additional musculoskeletal symptoms and/or skin abnormalities has a considerable stronger link to adult ADHD than non-specified GJH has, and may need awareness in ADHD management. Future studies should investigate the mechanisms behind this association and how comorbid GJH affects ADHD outcome.

  • 33.
    Goeterfelt, Linda
    et al.
    Orebro Univ, Sweden.
    Ekman, Carl Johan
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Hammar, Asa
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Landen, Mikael
    Karolinska Inst, Sweden; Gothenburg Univ, Sweden.
    Lundberg, Johan
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Nordanskog, Pia
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Nordenskjoeld, Axel
    Orebro Univ, Sweden.
    The Incidence of Dental Fracturing in Electroconvulsive Therapy in Sweden2020In: Journal of ECT, ISSN 1095-0680, E-ISSN 1533-4112, Vol. 36, no 3, p. 168-171Article in journal (Refereed)
    Abstract [en]

    Objectives 

    One adverse effect of electroconvulsive therapy (ECT) is dental fracture; thus, a bite guard and muscle relaxants are used to prevent it. Earlier research reported varying rates of dental fracture, but there is no large-scale study on the incidence of dental fracture during ECT. This study aimed to examine the incidence of dental fracture during ECT and to investigate whether the incidence differs between different sexes, age groups, diagnosis groups, electrode placements, or number of treatment sessions.

    Methods 

    This register-based study used data from the Swedish national quality register for ECT. All hospitals offering ECT report to this register, and the coverage ratio is about 90%. All registered patients who started an ECT series between January 2012 and January 2019 were included in this study, with the data representing 16,681 individuals, 38,862 series, and 254,906 sessions.

    Results 

    Forty-six dental fractures were identified, giving an incidence of dental fracture of 0.2% per series, 0.02% per session, and 0.3% per individual. We did not find any significant associations between dental fracture rates and male or female populations, age, or different diagnosis groups, nor was there any significant difference between dental fracture rates and electrode placement. The mean number of treatments was significantly higher in the dental fracture group than in patients without dental fracture.

    Conclusions 

    There is a minimal risk of dental fracture during ECT. Our findings, together with those of other studies, provide further motivation for the use of a bite guard and muscle relaxant.

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  • 34.
    Guney, Pelin
    et al.
    Orebro Univ, Sweden.
    Ekman, Carl Johan
    Karolinska Inst, Sweden; Reg Stockholm, Sweden.
    Hammar, Asa
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Heintz, Emelie
    Karolinska Inst, Sweden.
    Landen, Mikael
    Karolinska Inst, Sweden; Gothenburg Univ, Sweden.
    Lundberg, Johan
    Karolinska Inst, Sweden; Reg Stockholm, Sweden.
    Nordanskog, Pia
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Nordenskjold, Axel
    Orebro Univ, Sweden.
    Electroconvulsive Therapy in Depression Improvement in Quality of Life Depending on Age and Sex2020In: Journal of ECT, ISSN 1095-0680, E-ISSN 1533-4112, Vol. 36, no 4, p. 242-246Article in journal (Refereed)
    Abstract [en]

    Objectives: It is uncertain if there are variations in the improvement of quality in life between sexes and age groups after electroconvulsive therapy (ECT). The aim of this study was to investigate how health-related quality of life changed after treatment and to examine differences in the results between sex and age groups. Methods: This register-based study used data from the Swedish national quality register for ECT. The study population was patients diagnosed with depression who had received ECT. Health-related quality of life was quantified using the 3-level version the EuroQol 5-dimensional questionnaire (EQ-5D 3 L). Analysis of variance was used to compare change in EQ-5D score from pretreatment to posttreatment between sex and age groups. Results: There was a statistically significant improvement in EQ-5D index score and EQ visual analog scale (VAS) score in all patient groups after ECT. The mean improvement in EQ-5D index score and EQ-VAS score ranged from 0.31 to 0.46 and 28.29 to 39.79, respectively. Elderly patients had greater improvement in EQ-5D index score and EQ-VAS score than younger patients. There was no significant difference in improvement between the sexes. The mean improvement in EQ-5D index score was 0.40 for male patients and 0.41 for female patients. Conclusions: Electroconvulsive therapy had a considerable effect on health-related quality of life in patients with depression of both sexes and all age groups. The improvement was greatest in elderly patients, who more often had psychotic features. More studies are needed to investigate the long-term effects of ECT and to further explain the varying treatment results between elderly and younger patients.

  • 35.
    Hansen, Johan Liseth
    et al.
    Quantify Res, Sweden; Univ Oslo, Norway.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Kalso, Eija
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Stubhaug, Audun
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Knutsson, Douglas
    Quantify Res, Sweden.
    Sandin, Patrik
    Quantify Res, Sweden.
    Dorling, Patricia
    Pfizer Inc, NY USA.
    Beck, Craig
    Pfizer Ltd, England.
    Grip, Emilie Toresson
    Quantify Res, Sweden; Karolinska Inst, Sweden.
    Blakeman, Karin Hygge
    Pfizer AB, Sweden.
    Arendt-Nielsen, Lars
    Aalborg Univ, Denmark.
    Problematic opioid use among osteoarthritis patients with chronic post-operative pain after joint replacement: analyses from the BISCUITS study2023In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 23, no 2, p. 353-363Article in journal (Refereed)
    Abstract [en]

    Objectives: Opioids are commonly used to manage pain, despite an increased risk of adverse events and complications when used against recommendations. This register study uses data of osteoarthritis (OA) patients with joint replacement surgery to identify and characterize problematic opioid use (POU) prescription patterns.Methods: The study population included adult patients diagnosed with OA in specialty care undergoing joint replacement surgery in Denmark, Finland, Norway, and Sweden during 1 January 2011 to 31 December 2014. Those with cancer or OA within three years before the first eligible OA diagnosis were excluded. Patients were allocated into six POU cohorts based on dose escalation, frequency, and dosing of prescription opioids post-surgery (definitions were based on guidelines, previous literature, and clinical experience), and matched on age and sex to patients with opioid use, but not in any of the six cohorts. Data on demographics, non-OA pain diagnoses, cardiovascular diseases, psychiatric disorders, and clinical characteristics were used to study patient characteristics and predictors of POU.Results: 13.7% of patients with OA and a hip/knee joint replacement were classified as problematic users and they had more comorbidities and higher pre-surgery doses of opioids than matches. Patients dispensing high doses of opioids pre-surgery dispensed increased doses post-surgery, a pattern not seen among patients prescribed lower doses pre-surgery. Being dispensed 1-4,500 oral morphine equivalents in the year pre-surgery or having a non-OA pain diagnosis was associated with post-surgery POU (OR: 1.44-1.50, and 1.11-1.20, respectively).Conclusions: Based on the discovered POU predictors, the study suggests that prescribers should carefully assess pain management strategies for patients with a history of comorbidities and pre-operative, long-term opioid use. Healthcare units should adopt risk assessment tools and ensure that these patients are followed up closely. The data also demonstrate potential areas for further exploration in improving patient outcomes and trajectories.

  • 36.
    Harel, Maayan
    et al.
    Ben Gurion Univ Negev, Israel; Ben Gurion Univ Negev, Israel.
    Perini, Irene
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Kämpe, Robin
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Alyagon, Uri
    Ben Gurion Univ Negev, Israel; Ben Gurion Univ Negev, Israel.
    Shalev, Hadar
    Ben Gurion Univ Negev, Israel; Ben Gurion Univ Negev, Israel; Soroka Med Ctr, Israel.
    Besser, Itay
    Ben Gurion Univ Negev, Israel; Ben Gurion Univ Negev, Israel; Soroka Med Ctr, Israel.
    Sommer, Wolfgang H.
    Heidelberg Univ, Germany; Bethanien Hosp Psychiat Psychosomat & Psychothera, Germany.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Zangen, Abraham
    Ben Gurion Univ Negev, Israel; Ben Gurion Univ Negev, Israel.
    Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized, Double-Blind, Sham-Controlled Proof-of-Concept Trial Targeting the Medial Prefrontal and Anterior Cingulate Cortices2022In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 91, no 12, p. 1061-1069Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Alcohol addiction is associated with a high disease burden, and treatment options are limited. In a proof-of-concept study, we used deep repetitive transcranial magnetic stimulation (dTMS) to target circuitry associated with the pathophysiology of alcohol addiction. We evaluated clinical outcomes and explored associated neural signatures using functional magnetic resonance imaging. METHODS: This was a double-blind, randomized, sham-controlled trial. A total of 51 recently abstinent treatment-seeking patients with alcohol use disorder (moderate to severe) were randomized to sham or active dTMS, using an H7 coil targeting midline frontocortical areas, including the medial prefrontal and anterior cingulate cortices. Treatment included 15 sessions over 3 weeks, followed by five sessions over 3 months of follow-up. Each session delivered 100 trains of 30 pulses at 10 Hz. The primary predefined outcome was reduction in percentage of heavy drinking days, obtained using timeline follow-back interviews. Secondary analyses included self-reports of craving, ethyl glucuronide in urine, and brain imaging measures. RESULTS: Both craving after treatment and percentage of heavy drinking days during follow-up were significantly lower in the active versus sham control group (percentage of heavy drinking days = 2.9 +/- 0.8% vs. 10.6 +/- 1.9%, p = .037). Active dTMS was associated with decreased resting-state functional connectivity of the dorsal anterior cingulate cortex with the caudate nucleus and decreased connectivity of the medial prefrontal cortex to the subgenual anterior cingulate cortex. CONCLUSIONS: We provide initial proof-of-concept for dTMS targeting midline frontocortical structures as a treatment for alcohol addiction. These data strongly support a rationale for a full-scale confirmatory multicenter trial. Therapeutic benefits of dTMS appear to be associated with persistent changes in brain network activity.

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  • 37.
    Hedén, Ludwig
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Jonsson, Linda S.
    Marie Cederschiold Univ, Sweden.
    Fredlund, Cecilia
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    The Connection Between Sex as Self-Injury and Sexual Violence2023In: Archives of Sexual Behavior, ISSN 0004-0002, E-ISSN 1573-2800, Vol. 52, p. 3531-3540Article in journal (Refereed)
    Abstract [en]

    Nonsuicidal self-injury (NSSI) is a suggested diagnosis recognized by DSM-5 as in need of further research. Recent studies conclude that sex as self-injury (SASI) and NSSI share similar functions, such as being used as emotional regulation. SASI has been associated with earlier sexual abuse, but the understanding of the association between sexual violence and SASI is still limited. The aim of this study was to further investigate the connection between sexual violence and the experience of SASI. How could SASI be related to sexual violence? The study used a qualitative design and was based on an anonymous questionnaire published on the websites of Swedish NGOs, providing help and support to women and youths, such as those in womens shelters. In total, 139 informants with a mean age of 27.9 years (range 15-64 years) were included in the study. Three main themes were found: (1) Normalization of sexual violence and a shift in boundaries could be seen as consequences of earlier experiences of sexual violence leading to SASI; (2) SASI could escalate into sexual violence through increased need of emotional regulation, increased risk-taking, and risk of victimization; (3) SASI could be used to regain control of re-experiences, the body, sexuality, and shame after sexual abuse. In conclusion, a complex connection was identified whereby SASI could escalate into sexual violence, and earlier experiences of sexual violence could lead to SASI in a vicious loop. Hence, SASI should be seen as a risk factor for further victimization and sexual abuse.

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  • 38.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Startrek: The Next Generation of Alcohol Researchers: A Perspective from Markus Heilig, 2019 Recipient of the ESBRA Manfred Lautenschlager-European Alcohol Research Award2021In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 56, no 2, p. 125-126Article in journal (Other academic)
    Abstract [en]

    n/a

  • 39.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Stress-related neuropeptide systems as targets for treatment of alcohol addiction: A clinical perspective2023In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 293, no 5, p. 559-573Article, review/survey (Refereed)
    Abstract [en]

    Alcohol use is a major cause of disability and death globally. These negative consequences disproportionately affect people who develop alcohol addiction, a chronic relapsing condition characterized by increased motivation to use alcohol, choice of alcohol over healthy, natural rewards, and continued use despite negative consequences. Available pharmacotherapies for alcohol addiction are few, have effect sizes in need of improvement, and remain infrequently prescribed. Research aimed at developing novel therapeutics has in large part focused on attenuating pleasurable or "rewarding" properties of alcohol, but this targets processes that primarily play a role as initiation factors. As clinical alcohol addiction develops, long-term changes in brain function result in a shift of affective homeostasis, and rewarding alcohol effects become progressively reduced. Instead, increased stress sensitivity and negative affective states emerge in the absence of alcohol and create powerful incentives for relapse and continued use through negative reinforcement, or "relief." Based on research in animal models, several neuropeptide systems have been proposed to play an important role in this shift, suggesting that these systems could be targeted by novel medications. Two mechanisms in this category, antagonism at corticotropin-releasing factor type 1, and neurokinin 1/substance P receptors, have been subject to initial evaluation in humans. A third, kappa-opioid receptor antagonism, has been evaluated in nicotine addiction and could soon be tested for alcohol. This paper discusses findings with these mechanisms to date, and their prospects as future targets for novel medications.

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  • 40.
    Heilig, Markus
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Barbier, Estelle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Cycles of addiction and loneliness2022In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 110, no 24, p. 4035-4037Article in journal (Other academic)
    Abstract [en]

    In this issue of Neuron, Pomrenze and colleagues(1) report a novel mechanism behind sociability deficits in mice during protracted withdrawal from morphine. Dorsal raphe dynorphin neurons terminating in the nucleus accumbens suppress local serotonin release through kappa opioid receptors. These findings likely have important clinical implications.

  • 41.
    Heilig, Markus
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    MacKillop, James
    McMaster Univ, Canada; St Josephs Healthcare Hamilton, Canada; Homewood Res Inst, Canada.
    Martinez, Diana
    New York State Psychiat Inst & Hosp, NY 10032 USA; Columbia Univ, NY USA.
    Rehm, Juergen
    Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto UofT, Canada; Univ Toronto UofT, Canada; Tech Univ Dresden, Germany; IM Sechenov First Moscow State Med Univ, Russia.
    Leggio, Lorenzo
    NIDA, MD USA; NIAAA, MD USA.
    Vanderschuren, Louk J. M. J.
    Univ Utrecht, Netherlands.
    Response to "Addiction is a social disease: just as tenable as calling it a brain disease"2021In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 46, p. 1713-1714Article in journal (Other academic)
    Abstract [en]

    n/a

  • 42.
    Heilig, Markus
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    MacKillop, James
    McMaster Univ, Canada; St Josephs Healthcare Hamilton, Canada; Homewood Res Inst, Canada.
    Martinez, Diana
    New York State Psychiat Inst & Hosp, NY 10032 USA; Columbia Univ, NY USA.
    Rehm, Jurgen
    Ctr Addict & Mental Hlth CAMH, Canada; Ctr Addict & Mental Hlth CAMH, Canada; Univ Toronto UofT, Canada; Univ Toronto UofT, Canada; Tech Univ Dresden, Germany; IM Sechenov First Moscow State Med Univ, Russia.
    Leggio, Lorenzo
    NIDA, MD USA; NIAAA, MD USA.
    Vanderschuren, Louk J. M. J.
    Univ Utrecht, Netherlands.
    Addiction as a brain disease revised: why it still matters, and the need for consilience2021In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 46, no 10, p. 1715-1723Article, review/survey (Refereed)
    Abstract [en]

    The view that substance addiction is a brain disease, although widely accepted in the neuroscience community, has become subject to acerbic criticism in recent years. These criticisms state that the brain disease view is deterministic, fails to account for heterogeneity in remission and recovery, places too much emphasis on a compulsive dimension of addiction, and that a specific neural signature of addiction has not been identified. We acknowledge that some of these criticisms have merit, but assert that the foundational premise that addiction has a neurobiological basis is fundamentally sound. We also emphasize that denying that addiction is a brain disease is a harmful standpoint since it contributes to reducing access to healthcare and treatment, the consequences of which are catastrophic. Here, we therefore address these criticisms, and in doing so provide a contemporary update of the brain disease view of addiction. We provide arguments to support this view, discuss why apparently spontaneous remission does not negate it, and how seemingly compulsive behaviors can co-exist with the sensitivity to alternative reinforcement in addiction. Most importantly, we argue that the brain is the biological substrate from which both addiction and the capacity for behavior change arise, arguing for an intensified neuroscientific study of recovery. More broadly, we propose that these disagreements reveal the need for multidisciplinary research that integrates neuroscientific, behavioral, clinical, and sociocultural perspectives.

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  • 43.
    Iliadis, Stavros I.
    et al.
    Uppsala Univ, Sweden.
    Axfors, Cathrine
    Uppsala Univ, Sweden.
    Friberg, Agnes
    Uppsala Univ, Sweden.
    Arinell, Hans
    Uppsala Univ, Sweden.
    Beckman, Ulrika
    Sodra Alvsborgs Hosp, Sweden.
    Fazekas, Attila
    Lund Univ, Sweden.
    Frisen, Louise
    Karolinska Inst, Sweden.
    Sandstroem, Lotta
    Umea Univ, Sweden.
    Thelin, Nils
    Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Wahlberg, Jeanette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
    Sodersten, Maria
    Karolinska Inst, Sweden.
    Papadopoulos, Fotios C.
    Uppsala Univ, Sweden.
    Psychometric properties and concurrent validity of the Transgender Congruence Scale (TCS) in the Swedish setting2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 18701Article in journal (Refereed)
    Abstract [en]

    The Transgender Congruence Scale (TCS) is a non-binary tool used in Sweden for gender dysphoria (GD) assessment; however, its Swedish version has not been validated. To investigate the psychometric properties of the TCS, its capacity to distinguish individuals with GD and its concurrent validity compared to other scales. Patients with GD (n=135) and controls (n=443) filled in a questionnaire containing sociodemographic questions, the TCS, the Utrecht Gender Dysphoria Scale (UGDS), and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). TCS had good discriminatory validity and internal consistency. Patients with GD, stratified by birth-assigned sex, had lower TCS scores compared to controls. Confirmatory factor analysis (CFA) supported the two-factor model of the TCS. Multiple-group CFA suggested measurement invariance between birth-assigned sexes and configural invariance between patients with GD and controls. Area under the ROC curve for birth-assigned males was 0.991 and for females 0.994. A TCS mean value of three provided sensitivity 94.3% and 95.1% as well as specificity 98.6% and 98% for aM and aF, respectively. The TCS was significantly correlated to UGDS and GIDYQ-AA. The TCS may be a valuable tool in the clinical assessment of individuals with GD.

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  • 44.
    Jaarsma, Pier
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Gelhaus, Petra
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Eklund Saksberg, My
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences.
    Two cases of nursing older nursing home residents during COVID-192023In: Nursing Ethics, ISSN 0969-7330, E-ISSN 1477-0989Article in journal (Refereed)
    Abstract [en]

    Introduction Two ethical challenges of nursing home nurses during the COVID-19 pandemic in Sweden are discussed in this paper. Background Historically, the nurses primary concern is for the person who is ill, which is the core of nurses moral responsibility and identity. In Sweden, person-centered care is generally deemed important in nursing older nursing home residents. Objective To chart moral responsibilities of nursing home nurses in two cases involving older residents during the COVID-19 pandemic in Sweden. Methods We used Margaret Urban Walkers framework for moral responsibilities and the International Council of Nurses (ICN) code of ethics for nurses (2021) for our normative analysis. Ethical considerations Written and verbal consent was obtained before the interviews, and information was given that participation was entirely voluntary and possible to cancel at any time before the work was published. The Swedish Ethical Review Agency gave an advisory opinion stating that there were no ethical objections to this research project (Dnr. 2020-05649). Findings Case #1: a palliative older nursing home resident who was coercively tested for COVID-19, and case #2: a COVID-19-infected resident with dementia who was isolated using sedation. The decision that was finally made in the respective case was analyzed in the light of either consequentialist/utilitarian or non-consequentialist/deontological reasons. Discussion Empowerment of nurses as moral agents is required for the application of practical wisdom in the balancing of different care relationships (responsibilities), moral identities (professional virtues), and competing moral values. This requires resources and opens possibilities for profound ethical reflection in nursing education and at work. Conclusion During the COVID-19 pandemic, the moral and professional responsibility of nursing home nurses to deliver person-centered care was sometimes problematically abandoned in favor of a more utilitarian manner of ethical decision-making.

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  • 45.
    Johansson Capusan, Andrea
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Gustafsson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Kuja-Halkola, Ralf
    Karolinska Inst, Sweden.
    Igelström, Kajsa
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Mayo, Leah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Re-examining the link between childhood maltreatment and substance use disorder: a prospective, genetically informative study2021In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, no 7, p. 3201-3209Article in journal (Refereed)
    Abstract [en]

    Childhood maltreatment is considered a risk factor for substance use disorders (SUD), but this is largely based on retrospective self-reports that are subject to recall bias, designs that do not control for familial confounding, or both. The specific contribution of childhood maltreatment to SUD risk thus remains unclear. Here, we evaluated this contribution in a prospective cohort with objectively recorded childhood maltreatment, using a design that allows controlling for familial confounding. We used medical records and registers to study 525 young adults (20-37 years) with prospectively and objectively documented severe maltreatment exposure, 1979 clinical controls (unexposed former child and adolescent psychiatry patients), 1388 matched healthy controls; and their siblings and cousins. We examined the association between maltreatment and SUD using Cox regression models in the population, as well as stratified within siblings in the same family. SUD risk was significantly increased with childhood maltreatment exposure (crude HR: 6.61, 95% CI: 5.81-7.53; HR adjusted for sex, birthyear, externalizing problems, parents SUD and socioeconomic factors: 3.50, 95% CI 2.95, 4.16). An approximately threefold elevated SUD risk remained when comparing exposed individuals with their unexposed siblings (adjusted HR: 3.12, 95% CI 2.21, 4.42). We provide estimates of the association between childhood maltreatment and SUD accounting for possible confounds of both recall bias and familial factors. When familial confounding is controlled for, SUD risk attributable to severe childhood maltreatment is decreased, but nevertheless considerable. These findings establish a specific contribution of childhood maltreatment to SUD, underscoring the need for SUD prevention in young people exposed to maltreatment.

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  • 46.
    Johansson Capusan, Andrea
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Guterstam, Joar
    Beroendecent­rum Stockholm, Sverige; Institutionen för klinisk neurovetenskap, Centrum för psykiatriforskning, Karolinska institutet, Stockholm, Sverige.
    Ginsberg, Ylva
    Centrum för psykiatriforskning, Karolinska institutet, Stockholm, Sverige; Socialstyrelsen, Sverige.
    Borg Skoglund, Lotta
    Uppsala universitet, Sverige; Smart psykiatri, Stockholm, Sverige.
    Den mörka sidan – ADHD vanligt vid substansbruk och kriminalitet: [The dark side of ADHD - comorbidity with substance use disorder and criminality - an overview]2022In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 119, article id 21105Article, review/survey (Refereed)
    Abstract [sv]

    ADHD frequently co-occurs with substance use disorder (SUD) and is also common in prison populations. Screening and structured diagnosis should therefore be made available to treatment seeking SUD patients as well as to prison inmates. Multimodal, integrated treatment, including appropriate pharmacological and psychosocial therapies, is recommended for both ADHD and SUD. Long-acting stimulants with lower misuse potential are first line treatment for ADHD, with research indicating that somewhat higher stimulant doses could be necessary in this population. Increased frequency of underlying cardiovascular conditions, as well as increased risks for medication misuse in SUD populations, warrant careful treatment monitoring. There is no evidence suggesting that stimulant treatment increases risk for SUD. Given its high prevalence in prison settings, diagnosis of and integrated pharmacological and psychosocial treatment  for ADHD may decrease SUD relapse and criminality in those incarcerated.

  • 47.
    Johnson, Björn
    et al.
    Malmö Univ, Sweden.
    Flensburg, Olivia Liahaugen
    Malmö Univ, Sweden.
    Johansson Capusan, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Patient perspectives on depot buprenorphine treatment for opioid addiction - a qualitative interview study2022In: Substance Abuse Treatment, Prevention, and Policy, E-ISSN 1747-597X, Vol. 17, no 1, article id 40Article in journal (Refereed)
    Abstract [en]

    Background: Recently developed buprenorphine depot injections have the potential to reduce risk for diversion and misuse, and to increase adherence with fewer visits for supervised intake. However, it is unclear how patients perceive this new form of medication. The purpose of this study was to explore patients experiences of depot injections and their reasons for continuing, discontinuing, or declining depot injection treatment.

    Methods: We conducted semi-structured qualitative interviews with 32 people, 14 of whom had ongoing depot injection treatment, 11 who had discontinued depot-injections and switched to other medication and seven who had declined treatment with depot formulations. Interviews were transcribed, coded, and analysed using NVivo, based on this overall stratification into three participant groups.

    Results: The main categories relate to the effects and side effects of the depot formulation, social and practical factors, psychological benefits and disadvantages, and interactions with treatment staff. Social and practical factors were of importance for choosing depot formulations, such as increased freedom and their making it easier to combine treatment with work and family life, as well as psychological advantages including "feeling normal". Initial withdrawal symptoms that resolved themselves after a number of injections were reported by most participants. Reliable information and patient-staff relationships characterized by trust helped patients to cope with these initial problems. Those who discontinued treatment often did so near the beginning of the treatment, reporting withdrawal symptoms and insufficient effects as the main reasons. Coercion and insufficient information contributed to a negative pharmaceutical atmosphere at one of the clinics, which may have adversely influenced perceptions of depot formulations and decreased willingness to accept and continue treatment.

    Conclusions: Buprenorphine depot injections may have social, practical, and psychological benefits compared to other formulations. However, depot injections are not perceived as an attractive option by all patients. Trust, consistent and adequate information, and awareness of the implications of the pharmaceutical atmosphere should be considered when introducing new medications.

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  • 48.
    Johnson, Björn
    et al.
    Lund Univ, Sweden.
    Monwell, Bodil
    Cty Hosp Jonkoping, Sweden; Jonkoping Univ, Sweden.
    Johansson Capusan, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Long-acting injectable depot buprenorphine from a harm reduction perspective in patients with ongoing substance use and multiple psychiatric comorbidities: a qualitative interview study2024In: Harm Reduction Journal, E-ISSN 1477-7517, Vol. 21, no 1, article id 68Article in journal (Refereed)
    Abstract [en]

    Background Long-acting injectable depot buprenorphine may increase access to opioid agonist treatment (OAT) for patients with opioid use disorder in different treatment phases. The aim of this study was to explore the experiences of depot buprenorphine among Swedish patients with ongoing substance use and multiple psychiatric comorbidities.Method Semi-structured qualitative interviews were conducted with OAT patients with experience of depot buprenorphine. Recruitment took place at two OAT clinics with a harm reduction focus, specializing in the treatment of patients with ongoing substance use and multiple comorbidities. Nineteen participants were included, 12 men and seven women, with a mean age of 41 years (range 24-56 years), and a mean of 21 years (5-35 years) of experience with illicit substance use. All participants had ongoing substance use and psychiatric comorbidities such as ADHD, anxiety, mood, psychotic and eating disorders. Interviews were transcribed verbatim. Thematic content analysis was conducted both manually and using qualitative data analysis software.Results Participants reported social benefits and positive changes in self-perception and identity. In particular, depot buprenorphine contributed to a realization that it was possible to make life changes and engage in activities not related to substance use. Another positive aspect that emerged from the interviews was a noticeable relief from perceived pressure to divert OAT medication, while some expressed the lack of income from diverted oral/sublingual OAT medication as a negative, but still acceptable, consequence of the depot buprenorphine. Many participants considered that the information provided prior to starting depot buprenorphine was insufficient. Also, not all patients found depot buprenorphine suitable, and those who experienced coercion exhibited particularly negative attitudes towards the medication.Conclusions OAT patients with ongoing substance use and multiple psychiatric comorbidities reported clear benefits of depot buprenorphine, including changes in self-perception which has been theorized to play an important role in recovery. Clinicians should consider the specific information needs of this population and the extensive diversion of traditional OAT medications in this population to improve the treatment experience and outcomes. Overall, depot buprenorphine is a valuable treatment option for a population in need of harm reduction and may also contribute to psychological changes that may facilitate recovery in those with the greatest need.

  • 49.
    Johnstone, Andrea L.
    et al.
    Univ Miami, FL 33136 USA; Univ Miami, FL 33136 USA; EpiCypher Inc, NC USA.
    Andrade, Nadja S.
    Univ Miami, FL 33136 USA.
    Barbier, Estelle
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Khomtchouk, Bohdan B.
    Univ Miami, FL 33136 USA; Univ Chicago, IL 60637 USA.
    Rienas, Christopher A.
    Univ Miami, FL 33136 USA.
    Lowe, Kenneth
    Univ Miami, FL 33136 USA.
    Van Booven, Derek J.
    Univ Miami, FL 33136 USA.
    Domi, Esi
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Esanov, Rustam
    Univ Miami, FL 33136 USA.
    Vilca, Samara
    Univ Miami, FL 33136 USA.
    Tapocik, Jenica D.
    NIAAA, MD USA.
    Rodriguez, Keli
    EpiCypher Inc, NC USA.
    Maryanski, Danielle
    EpiCypher Inc, NC USA.
    Keogh, Michael Christopher
    EpiCypher Inc, NC USA.
    Meinhardt, Marcus W.
    Heidelberg Univ, Germany.
    Sommer, Wolfgang H.
    Heidelberg Univ, Germany.
    Heilig, Markus
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Zeier, Zane
    Univ Miami, FL 33136 USA.
    Wahlestedt, Claes
    Univ Miami, FL 33136 USA.
    Dysregulation of the histone demethylase KDM6B in alcohol dependence is associated with epigenetic regulation of inflammatory signaling pathways2021In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, Vol. 26, no 1, article id e12816Article in journal (Refereed)
    Abstract [en]

    Epigenetic enzymes oversee long-term changes in gene expression by integrating genetic and environmental cues. While there are hundreds of enzymes that control histone and DNA modifications, their potential roles in substance abuse and alcohol dependence remain underexplored. A few recent studies have suggested that epigenetic processes could underlie transcriptomic and behavioral hallmarks of alcohol addiction. In the present study, we sought to identify epigenetic enzymes in the brain that are dysregulated during protracted abstinence as a consequence of chronic and intermittent alcohol exposure. Through quantitative mRNA expression analysis of over 100 epigenetic enzymes, we identified 11 that are significantly altered in alcohol-dependent rats compared with controls. Follow-up studies of one of these enzymes, the histone demethylase KDM6B, showed that this enzyme exhibits region-specific dysregulation in the prefrontal cortex and nucleus accumbens of alcohol-dependent rats. KDM6B was also upregulated in the human alcoholic brain. Upregulation of KDM6B protein in alcohol-dependent rats was accompanied by a decrease of trimethylation levels at histone H3, lysine 27 (H3K27me3), consistent with the known demethylase specificity of KDM6B. Subsequent epigenetic (chromatin immunoprecipitation [ChIP]-sequencing) analysis showed that alcohol-induced changes in H3K27me3 were significantly enriched at genes in the IL-6 signaling pathway, consistent with the well-characterized role of KDM6B in modulation of inflammatory responses. Knockdown of KDM6B in cultured microglial cells diminished IL-6 induction in response to an inflammatory stimulus. Our findings implicate a novel KDM6B-mediated epigenetic signaling pathway integrated with inflammatory signaling pathways that are known to underlie the development of alcohol addiction.

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  • 50.
    Kalling, Styrbjorn
    et al.
    Uppsala Univ, Sweden.
    Brus, Ole
    Orebro Univ, Sweden.
    Landen, Mikael
    Gothenburg Univ, Sweden; Karolinska Inst, Sweden.
    Lundberg, Johan
    Karolinska Inst, Sweden; Reg Stockholm, Sweden.
    Nordanskog, Pia
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Nordenskjold, Axel
    Orebro Univ, Sweden.
    Relapse risk after in-ward electroconvulsive therapy for acute polymorphic psychotic disorder2021In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 75, no 3, p. 201-206Article in journal (Refereed)
    Abstract [en]

    Purpose Acute polymorphic psychotic disorder (APPD) without symptoms of schizophrenia is a serious psychiatric condition. APPD can be effectively treated with electroconvulsive therapy (ECT), but little is known about relapse prevention after ECT for APPD. Materials and methods This was a retrospective register-based study conducted with 97 patients with APPD (ICD-10 diagnosis F23.0). We estimated the rates of readmission and suicide, and the prognostic factors of these outcomes after ECT. We combined data from several national Swedish registers and used Coxs regression analysis to identify demographic factors, disease characteristics, and relapse preventive treatments that predicted time to readmission or suicide (relapse). Data registered between 2011 and 2016 were used in the study. Results Twenty percent of cases relapsed within a year. Thereafter, relapse rate was low. Two cases died during follow-up, whereof one by suicide. Anxiolytic treatment, lamotrigine treatment, and having more than four previous psychiatric hospital admissions were associated with shorter time to relapse. The most robust of these associations was between anxiolytics and relapse risk. Conclusions The first year after discharge from APPD is the period associated with the highest risk of relapse. Having many previous admissions was associated to relapse risk after ECT for APPD. The associations between anxiolytics, lamotrigine, and relapse are uncertain and might be influenced by indication bias.

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