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  • 1.
    Brus, Ole
    et al.
    Orebro Univ, Sweden.
    Cao, Yang
    Orebro Univ, Sweden; Karolinska Inst, Sweden.
    Hammar, Asa
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Landen, Mikael
    Gothenburg Univ, Sweden; Karolinska Inst, Sweden.
    Lundberg, Johan
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Nordanskog, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Nordenskjold, Axel
    Orebro Univ, Sweden.
    Lithium for suicide and readmission prevention after electroconvulsive therapy for unipolar depression: population-based register study2019In: BJPsych Open, E-ISSN 2056-4724, Vol. 5, no 3, article id e46Article in journal (Refereed)
    Abstract [en]

    Background Electroconvulsive therapy (ECT) is effective for unipolar depression but relapse and suicide are significant challenges. Lithium could potentially lower these risks, but is used only in a minority of patients. Aims This study quantifies the effect of lithium on risk of suicide and readmission and identifies factors that are associate with readmission and suicide. Method This population-based register study used data from the Swedish National Quality Register for ECT and other Swedish national registers. Patients who have received ECT for unipolar depression as in-patients between 2011 and 2016 were followed until death, readmission to hospital or the termination of the study at the end of 2016. Cox regression was used to estimate hazard ratios (HR) of readmission and suicide in adjusted models. Results Out of 7350 patients, 56 died by suicide and 4203 were readmitted. Lithium was prescribed to 638 (9%) patients. Mean follow-up was 1.4 years. Lithium was significantly associated with lower risk of suicide (P = 0.014) and readmission (HR 0.84 95% CI 0.75-0.93). The number needed to be treated with lithium to prevent one readmission was 16. In addition, the following factors were statistically associated with suicide: male gender, being a widow, substance use disorder and a history of suicide attempts. Readmission was associated with young age, being divorced or unemployed, comorbid anxiety disorder, nonpsychotic depression, more severe symptoms before ECT, no improvement with ECT, not receiving continuation ECT or antidepressants, usage of antipsychotics, anxiolytics or benzodiazepines, severity of medication resistance and number of previous admissions. Conclusions More patients could benefit from lithium treatment.

  • 2.
    Carvalho, Andre F.
    et al.
    Ctr Addict and Mental Hlth, Canada; Univ Toronto, Canada.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Perez, Augusto
    Corp Nuevos Rumbos, Colombia.
    Probst, Charlotte
    Ctr Addict and Mental Hlth, Canada.
    Rehm, Jurgen
    Ctr Addict and Mental Hlth, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Ctr Addict and Mental Hlth, Canada; Tech Univ Dresden, Germany; Tech Univ Dresden, Germany; Sechenov First Moscow State Med Univ, Russia.
    Alcohol use disorders2019In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 394, no 10200, p. 781-792Article, review/survey (Refereed)
    Abstract [en]

    Alcohol use disorders consist of disorders characterised by compulsive heavy alcohol use and loss of control over alcohol intake. Alcohol use disorders are some of the most prevalent mental disorders globally, especially in high-income and upper-middle-income countries; and are associated with high mortality and burden of disease, mainly due to medical consequences, such as liver cirrhosis or injury. Despite their high prevalence, alcohol use disorders are undertreated partly because of the high stigma associated with them, but also because of insufficient systematic screening in primary health care, although effective and cost-effective psychosocial and pharmacological interventions do exist. Primary health care should be responsible for most treatment, with routine screening for alcohol use, and the provision of a staggered treatment response, from brief advice to pharmacological treatment. Clinical interventions for these disorders should be embedded in a supportive environment, which can be bolstered by the creation of alcohol control policies aimed at reducing the overall level of consumption.

  • 3.
    Domi, Esi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Camerino, Italy.
    Caputi, Francesca Felicia
    Alma Mater Studiorum Univ Bologna, Italy.
    Romualdi, Patrizia
    Alma Mater Studiorum Univ Bologna, Italy.
    Domi, Ana
    Univ Camerino, Italy.
    Scuppa, Giulia
    Univ Camerino, Italy.
    Candeletti, Sanzio
    Alma Mater Studiorum Univ Bologna, Italy.
    Atkins, Alison Lynn
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Demopulos, Gregory
    Omeros Corp, WA 98101 USA.
    Gaitanaris, George
    Omeros Corp, WA 98101 USA.
    Ciccocioppo, Roberto
    Univ Camerino, Italy.
    Ubaldi, Massimo
    Univ Camerino, Italy.
    Activation of PPAR gamma Attenuates the Expression of Physical and Affective Nicotine Withdrawal Symptoms through Mechanisms Involving Amygdala and Hippocampus Neurotransmission2019In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 39, no 49, p. 9864-9875Article in journal (Refereed)
    Abstract [en]

    An isoform of peroxisome proliferator-activated receptors (PPARs), PPAR gamma, is the receptor for the thiazolidinedione class of antidiabetic medications including pioglitazone. Neuroanatomical data indicate PPAR gamma localization in brain areas involved in drug addiction. Preclinical and clinical data have shown that pioglitazone reduces alcohol and opioid self-administration, relapse to drug seeking, and plays a role in emotional responses. Here, we investigated the behavioral effect of PPAR gamma manipulation on nicotine withdrawal in male Wistar rats and in male mice with neuron-specific PPAR gamma deletion (PPAR gamma(()(+/+)())) and their littermate wild-type (PPAR gamma((-/-))) controls. Real-time quantitative RT-PCR and RNAscope in situ hybridization assays were used for assessing the levels of expression and cell-type localization of PPAR gamma function, Memory, Mortality, Older subjects, Structural brain abnormalities during nicotine withdrawal. Brain site-specific microinjections of the PPAR gamma agonist pioglitazone were performed to explore the role of this system on nicotine withdrawal at a neurocircuitry level. Results showed that activation of PPAR gamma by pioglitazone abolished the expression of somatic and affective nicotine withdrawal signs in rats and in (PPAR gamma(()(+/+)())) mice. This effect was blocked by the PPAR gamma antagonist GW9662. During early withdrawal and protracted abstinence, the expression of PPAR gamma increased in GABAergic and glutamatergic cells of the amygdala and hippocampus, respectively. Hippocampal microinjections of pioglitazone reduced the expression of the physical signs of withdrawal, whereas excessive anxiety associated with protracted abstinence was prevented by pioglitazone microinjection into the amygdala. Our results demonstrate the implication of the neuronal PPAR gamma in nicotine withdrawal and indicates that activation of PPAR gamma may offer an interesting strategy for smoking cessation.

  • 4.
    Filipcic, Igor
    et al.
    Psychiat Hosp Sveti Ivan, Croatia; Josip Juraj Strossmayer Univ Osijek, Croatia; Univ Zagreb, Croatia.
    Filipcic, Ivona Simunovic
    Univ Hosp Ctr Zagreb, Croatia.
    Milovac, Zeljko
    Psychiat Hosp Sveti Ivan, Croatia.
    Sucic, Strahimir
    Psychiat Hosp Sveti Ivan, Croatia.
    Gajsak, Tomislav
    Psychiat Hosp Sveti Ivan, Croatia.
    Ivezic, Ena
    Psychiat Hosp Sveti Ivan, Croatia; Josip Juraj Strossmayer Univ Osijek, Croatia.
    Basic, Silvio
    Josip Juraj Strossmayer Univ Osijek, Croatia; Dubrava Univ Hosp, Croatia.
    Bajic, Zarko
    Psychiat Hosp Sveti Ivan, Croatia.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Efficacy of repetitive transcranial magnetic stimulation using a figure-8-coil or an H1-Coil in treatment of major depressive disorder; A randomized clinical trial2019In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 114, p. 113-119Article in journal (Refereed)
    Abstract [en]

    Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment option for major depressive disorder (MDD). However, comparisons of efficacy between the two FDA-approved protocols of rTMS modalities are lacking. The aim of this industry-independent, randomized-controlled, single-blind trial was to evaluate clinical outcome of the two FDA-approved rTMS protocols delivered by H1-coil and the figure-8-coil, in MDD patients. A total of 228 MDD patients were randomized to 20 sessions of H1-coil or 8-coil as an adjunct to standard-of-care pharmacotherapy, or standard-of-care pharmacotherapy alone. Baseline MDD symptom severity was almost the same in the three groups. Hamilton depression rating scale (HAM-D17) mean score was 17 (5.3) in H1-coil, 17 (5.4) in 8-coil, and 19 (6.1) in control group. The primary outcome was the proportion of patients achieving remission defined as HAM-D17 score amp;lt;= 7 at end-of-treatment at week-4. In the intention-to-treat analysis odds ratio for remission was 1.74 (CI95% 0.79-3.83) in H1-coil compared to the 8-coil group. The difference between two rTMS protocols was not significant. Remission rate was significantly greater in both HF-rTMS groups compared to the control: 60% (CI95% 48-71%), 43% (C195% 31-55%) and 11% (CI95% 5-20%) respectively. The response was significantly better in H1-coil, than in 8-coil group OR = 2.33; CI95% 1.04-5.21 (P = 0.040). The HAM-D17 was lowered by 59% in the H1-coil, 41% in the 8-coil (P = 0.048), and 17% in the control group (P amp;lt; 0.001 vs H1-coil; P = 0.003 vs 8-coil). Safety, tolerability, and the changes in quality of life were comparable. We confirmed the safety and efficacy of both FDA-approved protocols as adjunctive treatments of MDD. Better response rate and greater reduction of depression severity were observed in the H1-coil group, but without a significant difference in the remission rate between the two rTMS modalities.

  • 5.
    Fredlund, Cecilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Wadsby, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Jonsson, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Motives and Manifestations of Sex as Self-Injury2019In: Journal of Sex Research, ISSN 0022-4499, E-ISSN 1559-8519Article in journal (Refereed)
    Abstract [en]

    To view destructive sexual behaviors as a form of self-injury is a new concept in the research field that needs further exploration and conceptualization. The aim of this study was to explore experiences of sex as self-injury to identify motives and manifestations of the behavior. An anonymous self-selected open-ended questionnaire was used for the study, and qualitative content analysis was used to identify patterns and themes in the text. A total of 199 informants participated in the study (M = 27.9, SD = 9.3 years), all of whom were recruited via a range of websites of Swedish nongovernmental organizations. Sex as self-injury was described as voluntary exposure to sexual situations including psychological and/or physical harm. Affect regulation and receiving positive or negative confirmation emerged as important motives for the behavior. Respondents described sex as self-injury as difficult to stop when it felt compulsive and addictive, with ever-higher risk-taking and self-harming described. Our findings indicate that sex as self-injury often includes deliberate sexual violence, and is similar to other self-injurious behaviors, including non-suicidal self-injury. Sex as self-injury needs to be addressed in healthcare, such as in psychiatry and gynecology departments, to prevent further traumatization.

    The full text will be freely available from 2020-11-14 08:15
  • 6.
    Haglund, Lena
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Therese
    Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Andersson, Caroline
    Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    The use of MOHO intervention methods for enabling occupational change in mental health.2019Conference paper (Refereed)
    Abstract [en]

    The presented MOHO intervention methods; strategies and interventions, for facilitating change has not been investigated in practice in Sweden. MOHO is often seen as an assessment model. Many assessments have been translated and tested for scientific standard in Sweden but the intervention part has not been noticed in the same way. The aim of the presented survey was to investigate the use of the methods for facilitating change with MOHO in a Swedish context. Ten OT in the area of mental health were invited to partaken in the survey. In their daily work they reported on a questionnaire which methods they used if they were applying MOHO in the treatment sessions together with the client. Regarding therapeutic strategies in total 78 treatment sessions were reported. After following a treatment planning process including different MOHO assessments depending on the client ́s needs, it was stated that the main areas of concern for the clients were volition or habit or performance capacity to almost the same extent for all three elements. The result show that two of the strategies; “Validation” and “Identifying” was use most frequently. “Providing Physical Support” and “Negotiating” was used very sparingly. The most surprising result was that ”Structuring” was rated as number 6of the 9 strategies. When OT describe what they are doing, structuring daily occupations very often is mention as a regular intervention. The interventions are currently being tested, the results will be presented in September.

  • 7.
    Heilig, Markus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Augier, Eric
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Pfarr, Simone
    Cent Inst Mental Hlth, Germany.
    Sommer, Wolfgang H.
    Cent Inst Mental Hlth, Germany; Cent Inst Mental Hlth, Germany.
    Developing neuroscience-based treatments for alcohol addiction: A matter of choice?2019In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 9, article id 255Article, review/survey (Refereed)
    Abstract [en]

    Excessive alcohol use is the cause of an ongoing public health crisis, and accounts for -5% of global disease burden. A minority of people with recreational alcohol use develop alcohol addiction (hereafter equated with "alcohol dependence" or simply "alcoholism"), a condition characterized by a systematically biased choice preference for alcohol at the expense of healthy rewards, and continued use despite adverse consequences ("compulsivity"). Alcoholism is arguably the most pressing area of unmet medical needs in psychiatry, with only a small fraction of patients receiving effective, evidence-based treatments. Medications currently approved for the treatment of alcoholism have small effect sizes, and their clinical uptake is negligible. No mechanistically new medications have been approved since 2004, and promising preclinical results have failed to translate into novel treatments. This has contributed to a reemerging debate whether and to what extent alcohol addiction represents a medical condition, or reflects maladaptive choices without an underlying brain pathology. Here, we review this landscape, and discuss the challenges, lessons learned, and opportunities to retool drug development in this important therapeutic area.

  • 8.
    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 Clinical and Experimental Medicine, 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, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    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 pathways2019In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, article id UNSP 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.

  • 9.
    Jonsson, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Fredlund, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Priebe, Gisela
    Lund Univ, Sweden.
    Wadsby, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Online sexual abuse of adolescents by a perpetrator met online: a cross-sectional study2019In: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 13, no 1, article id 32Article in journal (Refereed)
    Abstract [en]

    Background

    The current study aimed at exploring adolescents’ experiences of online sexual contacts leading to online sexual abuse by a perpetrator whom the victim had first met online. Associations with socio demographic background, experience of abuse, relation to parents, health and risk behaviors were studied.

    Methods

    The participants were a representative national sample of 5175 students in the third year of the Swedish high school Swedish (M age = 17.97). Analyses included bivariate statistics and stepwise multiple logistic regression models.

    Results

    In total 330 (5.8%) adolescents had gotten to know someone during the preceding 12 months for the purpose of engaging in some kind of sexual activity online. Thirty-two (9.7%) of those, the index group, had felt that they had been persuaded, pressed or coerced on at least one occasion. Sexual interaction under pressure was seen as constituting sexual abuse. These adolescent victims of online sexual abuse, the index group, did not differ with respect to socio-demographic background from the adolescents without this experience, the reference group. The index group had significantly more prior experiences of different kind of abuse, indicating that they belong to a polyvictimized group. More frequent risk behavior, poorer psychological health, poorer relationships with parents and lower self-esteem also characterized the index group. Online sexual abuse, without experiences of offline abuse, was associated with a poorer psychological health, at least at the same level as offline sexual abuse only.

    Conclusions

    The study made clear the importance of viewing online sexual abuse as a serious form of sexual abuse. Professionals meeting these children need to focus not only on their psychological health such as symptoms of trauma and depression but also need to screen them for online behavior, online abuse and other forms of previous abuse.

  • 10.
    Josefsson, Ann
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Vikström, Josefin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    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.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, 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.
    Major depressive disorder in women and risk for future generations: population-based three-generation study2019In: BJPsych Open, E-ISSN 2056-4724, Vol. 5, no 1, article id e8Article in journal (Refereed)
    Abstract [en]

    Background The well-known adverse consequences of maternal depression prompts consideration of the importance of learning more about intergenerational transmission in order to identify individuals at risk of developing depressive disorders. Aims To follow two generations of women with major depressive disorder (MDD) and to examine the risk of MDD in the third-generation children. Method A register-based, retrospective cohort study of all women born in Sweden between 1973 and 1982 who had given birth during the study period, their mothers and their children. All generations were followed until 2013. Data was stratified into two cohorts: women born between 1973 and 1977 and those born between 1978 and 1982. Results Second-generation women were twice as likely to be diagnosed with MDD if their mothers had been diagnosed with MDD. If both previous generations had been diagnosed with depression the likelihood of the third-generation child being diagnosed with MDD was markedly increased (odds ratio (OR) = 5.07, 95% CI 4.06-6.34 and OR = 7.20, 95% CI 4.41-11.77 in cohort 1 and cohort 2, respectively). Conclusions There is a strong intergenerational impact in the transmission of MDD. The risk of MDD is especially high in individuals with MDD in both previous maternal generations.

  • 11.
    Lee, Mary R.
    et al.
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Tapocik, Jenica D.
    NIDA, MD 20892 USA.
    Ghareeb, Mwlod
    Univ Rhode Isl, RI 02881 USA.
    Schwandt, Melanie L.
    NIAAA, MD USA.
    Dias, Alexandra A.
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Le, April N.
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Cobbina, Enoch
    Univ Rhode Isl, RI 02881 USA.
    Farinelli, Lisa A.
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Bouhlal, Sofia
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Farokhnia, Mehdi
    NIAAA, MD 20892 USA; NIDA, MD 20892 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, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken. NIDA, MD 20892 USA.
    Akhlaghi, Fatemeh
    Univ Rhode Isl, RI 02881 USA.
    Leggio, Lorenzo
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA; Brown Univ, RI 02912 USA.
    The novel ghrelin receptor inverse agonist PF-5190457 administered with alcohol: preclinical safety experiments and a phase 1b human laboratory study2020In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 25, no 2, p. 461-475Article in journal (Refereed)
    Abstract [en]

    Rodent studies indicate that ghrelin receptor blockade reduces alcohol consumption. However, no ghrelin receptor blockers have been administered to heavy alcohol drinking individuals. Therefore, we evaluated the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and behavioral effects of a novel ghrelin receptor inverse agonist, PF-5190457, when co-administered with alcohol. We tested the effects of PF-5190457 combined with alcohol on locomotor activity, loss-of-righting reflex (a measure of alcohol sedative actions), and on blood PF-5190457 concentrations in rats. Then, we performed a single-blind, placebo-controlled, within-subject human study with PF-5190457 (placebo/0 mg b.i.d., 50 mg b.i.d., 100 mg b.i.d.). Twelve heavy drinkers during three identical visits completed an alcohol administration session, subjective assessments, and an alcohol cue-reactivity procedure, and gave blood samples for PK/PD testing. In rats, PF-5190457 did not interact with the effects of alcohol on locomotor activity or loss-of-righting reflex. Alcohol did not affect blood PF-5190457 concentrations. In humans, all adverse events were mild or moderate and did not require discontinuation or dose reductions. Drug dose did not alter alcohol concentration or elimination, alcohol-induced stimulation or sedation, or mood during alcohol administration. Potential PD markers of PF-5190457 were acyl-to-total ghrelin ratio and insulin-like growth factor-1. PF-5190457 (100 mg b.i.d.) reduced alcohol craving during the cue-reactivity procedure. This study provides the first translational evidence of safety and tolerability of the ghrelin receptor inverse agonist PF-5190457 when co-administered with alcohol. PK/PD/behavioral findings support continued research of PF-5190457 as a potential pharmacological agent to treat alcohol use disorder.

  • 12.
    Ljungvall, Hanna
    et al.
    Uppsala Univ, Sweden.
    Persson, Anna
    Karolinska Inst, Sweden.
    Asenlof, Pernilla
    Uppsala Univ, Sweden.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Ekselius, Lisa
    Uppsala Univ, Sweden.
    Reliability of the Addiction Severity Index self-report form (ASI-SR): a self-administered questionnaire based on the Addiction Severity Index composite score domains2019In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725Article in journal (Refereed)
    Abstract [en]

    Objectives: The Addiction Severity Index (ASI) is a standardized interview used to assess problems associated with substance use. Although widely used, the time required for the interview remains an obstacle to its acceptance in many clinical settings. We examined if a self-administered questionnaire based on the composite score (CS) items, the ASI Self-Report form (ASI-SR), offers a reliable alternative to the ASI in assessing current substance use and related problems. Methods: Participants were 59 treatment seeking individuals entering outpatient programs at the Addiction Psychiatric Clinic at Uppsala University Hospital who were assessed with Swedish versions of the ASI and ASI-SR. Agreement between the ASI interviews CS and ASI-SRs CS was evaluated on the individual basis by intraclass correlation analysis (ICC) and on group level with the Wilcoxon signed rank test. Reliability and internal consistency were evaluated using Cronbachs alpha. Results: For 6 out of 7 CS domains, the ICC for the ASI interview and ASI-SR were good to excellent. Internal consistency was acceptable for 6 out of 7 CS domains on the ASI interview and for 5 out of 7 CS domains on the ASI-SR. Conclusions: The present study suggests that the ASI-SR is a reliable alternative to the ASI interview for assessing current patient functioning and evaluation of problems related to alcohol and drug use.

  • 13.
    Ludvigsson, Mikael
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Milberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Advanced Home Care in Norrköping.
    Morbidity and mortality in very old individuals with subsyndromal depression: an 8-year prospective study2019In: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 31, no 11, p. 1569-1579, article id PII S1041610219001480Article in journal (Refereed)
    Abstract [en]

    Objectives: Both morbidity and mortality are elevated for individuals with subsyndromal depression (SSD) compared to non-depression (ND) in those of younger ages, but scientific studies are scarce for very old individuals. The aim of this study was therefore to compare the morbidity and mortality in very old individuals with SSD and ND. Design and setting: An 8-year prospective population-based study was undertaken on 85-year-old individuals in Sweden. Measurements: Data were collected from postal questionnaires and clinical assessments at baseline, after 1, 5, and 8 years. Depressive symptoms were measured with Geriatric Depression Scale and the results were classified into ND, SSD, and syndromal depression. Mortality was investigated using multivariable cox regressions, and variables of morbidity were investigated using linear mixed models. Results: Compared to ND, in people with SSD, mortality was elevated in the univariate regression, but this association vanished when controlling for relevant covariates. Morbidity was elevated with regard to basic activities of daily living (ADLs), instrumental ADLs, loneliness, self-perceived health, and depressive symptoms for individuals with SSD compared to ND, whereas cognitive speed, executive functions, and global cognitive function were not significantly impaired when adjusting for covariates. Conclusions: SSD among very old individuals is longitudinally associated with elevated morbidity but not mortality, when controlling for relevant covariates. Considering the high prevalence of SSD and the demographic development of increasing numbers of very old people, the findings highlight the need to develop clinical and societal strategies to prevent SSD and associated negative outcomes.

  • 14.
    Mayo, Leah
    et al.
    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.
    Lindé, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Morena, Maria
    Cummings Scool Med, Canada; Univ Calgary, Canada; Univ Calgary, Canada.
    Haataja, Roosa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Hammar, Valter
    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.
    Hill, Matthew N.
    Cummings Scool Med, Canada; Cummings Scool Med, Canada; Univ Calgary, Canada; Univ Calgary, Canada.
    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, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial2020In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 87, no 6, p. 538-547Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Posttraumatic stress disorder, an area of large unmet medical needs, is characterized by persistence of fear memories and maladaptive stress responses. In rodents, elevation of the endocannabinoid anandamide due to inhibition of fatty acid amide hydrolase (FAAH) facilitates fear extinction and protects against the anxiogenic effects of stress. We recently reported that elevated anandamide levels in people homozygous for a loss-of-function FAAH mutation are associated with a similar phenotype, suggesting a translational validity of the preclinical findings. METHODS: In this double-blind, placebo-controlled experimental medicine study, healthy adults were randomized to an FAAH inhibitor (PF-04457845, 4 mg orally, once daily; n = 16) or placebo (n = 29) for 10 days. On days 9 and 10, participants completed a task battery assessing psychophysiological indices of fear learning, stress reactivity, and stress-induced affective responses. RESULTS: FAAH inhibition produced a 10-fold increase in baseline anandamide. This was associated with potentiated recall of fear extinction memory when tested 24 hours after extinction training. FAAH inhibition also attenuated autonomic stress reactivity, assessed via electrodermal activity, and protected against stress-induced negative affect, measured via facial electromyography. CONCLUSIONS: Our data provide preliminary human evidence that FAAH inhibition can improve the recall of fear extinction memories and attenuate the anxiogenic effects of stress, in a direct translation of rodent findings. The beneficial effects of FAAH inhibition on fear extinction, as well as stress- and affect-related behaviors, provide a strong rationale for developing this drug class as a treatment for posttraumatic stress disorder.

  • 15.
    Mayo, Leah
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    In the face of stress: Interpreting individual differences in stress-induced facial expressions2019In: NEUROBIOLOGY OF STRESS, ISSN 2352-2895, Vol. 10, article id 100166Article, review/survey (Refereed)
    Abstract [en]

    Stress is an inevitable part of life that can profoundly impact social and emotional functioning, contributing to the development of psychiatric disease. One key component of emotion and social processing is facial expressions, which humans can readily detect and react to even without conscious awareness. Facial expressions have been the focus of philosophic and scientific interest for centuries. Historically, facial expressions have been relegated to peripheral indices of fixed emotion states. More recently, affective neuroscience has undergone a conceptual revolution, resulting in novel interpretations of these muscle movements. Here, we review the role of facial expressions according to the leading affective neuroscience theories, including constructed emotion and social-motivation accounts. We specifically highlight recent data (Mayo et al, 2018) demonstrating the way in which stress shapes facial expressions and how this is influenced by individual factors. In particular, we focus on the consequence of genetic variation within the endocannabinoid system, a neuromodulatory system implicated in stress and emotion, and its impact on stress-induced facial muscle activity. In a re-analysis of this dataset, we highlight how gender may also influence these processes, conceptualized as variation in the "fight-or-flight" or "tend-and-befriend" behavioral responses to stress. We speculate on how these interpretations may contribute to a broader understanding of facial expressions, discuss the potential use of facial expressions as a trans-diagnostic marker of psychiatric disease, and suggest future work necessary to resolve outstanding questions.

  • 16.
    Muench, Christine
    et al.
    NIAAA, MD 20892 USA.
    Charlet, Katrin
    NIAAA, MD 20892 USA.
    Balderston, Nicholas L.
    NIMH, MD 20892 USA.
    Grillon, Christian
    NIMH, MD 20892 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Cortes, Carlos R.
    NIAAA, MD 20892 USA.
    Momenan, Reza
    NIAAA, MD 20892 USA.
    Lohoff, Falk W.
    NIAAA, MD 20892 USA.
    Fear conditioning and extinction in alcohol dependence: Evidence for abnormal amygdala reactivity2019In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, article id UNSP e12835Article in journal (Refereed)
    Abstract [en]

    Fear conditioning and extinction (FCE) are vital processes in adaptive emotion regulation and disrupted in anxiety disorders. Despite substantial comorbidity between alcohol dependence (ALC) and anxiety disorders and reports of altered negative emotion processing in ALC, neural correlates of FCE in this clinical population remain unknown. Here, we used a 2-day fear learning paradigm in 43 healthy participants and 43 individuals with ALC at the National Institutes of Health. Main outcomes of this multimodal study included structural and functional brain magnetic resonance imaging, clinical measures, as well as skin conductance responses (SCRs) to confirm differential conditioning. Successful FCE was demonstrated across participants by differential SCRs in the conditioning phase and no difference in SCRs to the conditioned stimuli in the extinction phase. The ALC group showed significantly reduced blood oxygenation level-dependent responses in the right amygdala during conditioning (Cohens d = .89, P-(FWE) = .037) and in the left amygdala during fear renewal (Cohens d = .68, P-(FWE) = .039). Right amygdala activation during conditioning was significantly correlated with ALC severity (r = .39, P-(Bonferroni) = .009), depressive symptoms (r = .37, P-(Bonferroni) = .015), trait anxiety (r = .41, P-(Bonferroni) = .006), and perceived stress (r = .45, P-(Bonferroni) = .002). Our data suggest that individuals with ALC have dysregulated fear learning, in particular, dysregulated neural activation patterns, in the amygdala. Furthermore, amygdala activation during fear conditioning was associated with ALC-related clinical measures. The FCE paradigm may be a promising tool to investigate structures involved in negative affect regulation, which might inform the development of novel treatment approaches for ALC.

  • 17.
    Nelson, Britta S.
    et al.
    Univ Georgia, GA 30602 USA.
    Fulenwider, Hannah D.
    Univ Georgia, GA 30602 USA.
    Nennig, Sadie E.
    Univ Georgia, GA 30602 USA.
    Smith, Britessia M.
    Univ Georgia, GA 30602 USA.
    Sequeira, Michelle K.
    Univ Georgia, GA 30602 USA.
    Chimberoff, Scott H.
    Univ Georgia, GA 30602 USA.
    Richie, Christopher T.
    NIDA, MD 20892 USA.
    Cheng, Kejun
    NIAAA, MD USA; NIDA, MD 20892 USA; US FDA, MD USA.
    Rice, Kenner C.
    NIAAA, MD USA; NIDA, MD 20892 USA.
    Harvey, Brandon K.
    NIDA, MD 20892 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Schank, Jesse R.
    Univ Georgia, GA 30602 USA.
    Escalated Alcohol Self-Administration and Sensitivity to Yohimbine-lnduced Reinstatement in Alcohol Preferring Rats: Potential Role of Neurokinin-1 Receptors in the Amygdala2019In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 413, p. 77-85Article in journal (Refereed)
    Abstract [en]

    Genetic factors significantly contribute to the risk for developing alcoholism. To study these factors and other associated phenotypes, rodent lines have been developed using selective breeding for high alcohol preference. One of these models, the alcohol preferring (P) rat, has been used in hundreds of preclinical studies over the last few decades. However, very few studies have examined relapse-like behavior in this rat strain. In this study, we used operant self-administration and yohimbine-induced reinstatement models to examine relapse-like behavior in P rats. Our previous work has demonstrated that P rats show increased expression of the neurokinin-1 receptor (NK1R) in the central nucleus of the amygdala (CeA), and this functionally contributes to escalated alcohol consumption in this strain. We hypothesized that P rats would show increased sensitivity to yohimbine-induced reinstatement that is also mediated by NK1R in the CeA. Using Fos staining, site-specific infusion of NK1R antagonist, and viral vector overexpression, we examined the influence of NK1R on the sensitivity to yohimbine-induced reinstatement of alcohol seeking. We found that P rats displayed increased sensitivity to yohimbine-induced reinstatement as well as increased neuronal activation in the CeA after yohimbine injection compared to the control Wistar strain. Intra-CeA infusion of NK1R antagonist attenuates yohimbine-induced reinstatement in P rats. Conversely, upregulation of NK1R within the CeA of Wistar rats increases alcohol consumption and sensitivity to yohimbine-induced reinstatement. These findings suggest that NK1R upregulation in the CeA contributes to multiple alcohol-related phenotypes in the P rat, including alcohol consumption and sensitivity to relapse. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

  • 18.
    Ousdal, Olga Therese
    et al.
    Haukeland Hosp, Norway.
    Argyelan, Miklos
    Feinstein Inst Med Res, NY USA.
    Narr, Katherine L.
    Univ Calif Los Angeles, CA 90024 USA.
    Abbott, Christopher
    Univ New Mexico, NM 87131 USA.
    Wade, Benjamin
    Univ Calif Los Angeles, CA 90024 USA.
    Vandenbulcke, Mathieu
    Katholieke Univ Leuven, Belgium.
    Urretavizcaya, Mikel
    Univ Barcelona, Spain; Univ Barcelona, Spain; Carlos III Hlth Inst, Spain.
    Tendolkar, Indira
    Radboud Univ Nijmegen, Netherlands; Ctr Cognit Neuroimaging, Netherlands; Univ Duisburg Essen, Germany; Univ Duisburg Essen, Germany.
    Takamiya, Akihiro
    Keio Univ, Japan; Komagino Hosp, Japan.
    Stek, Max L.
    Geestelijke GezondheidsZorg InGeest Specialized M, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Soriano-Mas, Carles
    Univ Barcelona, Spain; Univ Autonoma Barcelona, Spain; Carlos III Hlth Inst, Spain.
    Redlich, Ronny
    Univ Munster, Germany.
    Paulson, Olaf B.
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Oudega, Mardien L.
    Geestelijke GezondheidsZorg InGeest Specialized M, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Opel, Nils
    Univ Munster, Germany; Univ Munster, 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, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Kishimoto, Taishiro
    Keio Univ, Japan.
    Kämpe, Robin
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Jorgensen, Anders
    Rigshosp, Denmark.
    Hanson, Lars G.
    Tech Univ Denmark, Denmark; Copenhagen Univ Hosp, Denmark.
    Hamilton, Paul
    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).
    Espinoza, Randall
    Univ Calif Los Angeles, CA 90024 USA.
    Emsell, Louise
    Katholieke Univ Leuven, Belgium.
    van Eijndhoven, Philip
    Radboud Univ Nijmegen, Netherlands; Ctr Cognit Neuroimaging, Netherlands.
    Dols, Annemieke
    Geestelijke GezondheidsZorg InGeest Specialized M, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Dannlowski, Udo
    Univ Munster, Germany.
    Cardoner, Narcis
    Univ Autonoma Barcelona, Spain; Carlos III Hlth Inst, Spain; Univ Hosp Parc Tauli I3PT, Spain.
    Bouckaert, Filip
    Katholieke Univ Leuven, Belgium.
    Anand, Amit
    Cleveland Clin, OH 44106 USA.
    Bartsch, Hauke
    Univ Calif Los Angeles, CA USA; Ctr Multimodal Imaging and Genet, CA USA; Univ Calif San Diego, CA 92093 USA.
    Kessler, Ute
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Oedegaard, Ketil J.
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Dale, Anders M.
    Univ Calif Los Angeles, CA USA; Ctr Multimodal Imaging and Genet, CA USA; Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA.
    Oltedal, Leif
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Brain Changes Induced by Electroconvulsive Therapy Are Broadly Distributed2020In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 87, no 5, p. 451-461Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response. METHODS: Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites. RESULTS: Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean +/- SD of 1.04 +/- 1.03% (Cohens d = 1.01, p amp;lt; .001) and the subcortical gray matter volume increased by 1.47 +/- 1.05% (d = 1.40, p amp;lt; .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearmans rank correlation rho = -.44, p amp;lt; .001), while total white matter volume remained unchanged (d = -0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome. CONCLUSIONS: The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.

  • 19.
    Perini, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Per A
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Hamilton, Paul J.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Kämpe, Robin
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Mayo, Leah M.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Zetterqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Brain-based Classification of Negative Social Bias in Adolescents With Nonsuicidal Self-injury: Findings From Simulated Online Social Interaction.2019In: EClinicalMedicine, ISSN 2589-5370, Vol. 13, p. 81-90Article in journal (Refereed)
    Abstract [en]

    Background: Interpersonal stress and perceived rejection have been clinically observed as common triggers of nonsuicidal self-injury (NSSI), with self-injury behavior regulating both affective and social experiences. We investigated whether the subjective interpretation of social interaction in a simulated online environment might be biased in the NSSI group, and the brain mechanisms underlying the experience.

    Methods: Thirty female adolescent patients with NSSI and thirty female age-matched controls were investigated in this case-control study. In our novel task that simulates interaction on current social media platforms, participants indicated whether they liked or disliked pictures of other players during a functional magnetic resonance imaging (fMRI) scan. Participants also viewed positive and negative feedback directed toward them by others. The task also assessed the subjective effects of the social interaction. Finally, subjects underwent a separate facial electromyography session, which measured facial expressions processing.

    Outcomes: Behaviorally, the NSSI group showed a negative bias in processing social feedback from others. A multi-voxel pattern analysis (MVPA) identified brain regions that robustly classified NSSI subjects and controls. Regions in which mutual activity contributed to the classification included dorsomedial prefrontal cortex and subgenual anterior cingulate cortex, a region implicated in mood control. In the NSSI group, multi-voxel classification scores correlated with behavioral sensitivity to negative feedback from others. Results remained significant after controlling for medication, symptoms of depression, and symptoms of borderline personality disorder.

    Interpretation: This study identified behavioral and neural signatures of adolescents with NSSI during social interaction in a simulated social media environment. These findings highlight the importance of understanding social information processing in this clinical population and can potentially advance treatment approaches.

  • 20.
    Persson, Emil
    et al.
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Asutay, Erkin
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Löfberg, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Pedersen, Nancy
    Karolinska Inst, Sweden.
    Västfjäll, Daniel
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Decis Res, OR USA.
    Tinghög, Gustav
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Variation in the mu-Opioid Receptor Gene (OPRM1) Does Not Moderate Social-Rejection Sensitivity in Humans2019In: Psychological Science, ISSN 0956-7976, E-ISSN 1467-9280, Vol. 30, no 7, p. 1050-1062Article in journal (Refereed)
    Abstract [en]

    Given previous findings from animal studies and small-scale studies in humans, variation in the mu-opioid receptor gene (OPRM1) has been proposed as a strong biological candidate for moderating sensitivity to social rejection. Using a substantially larger sample (N = 490) than previous studies, a prospective genotyping strategy, and preregistered analysis plans, we tested the hypotheses that OPRM1 variation measured by the functional A118G polymorphism (rs1799971) moderates (a) dispositional sensitivity to rejection and feelings of distress following social exclusion and (b) decision making involving social cognition. In three experimental tasks commonly used to assess altruism, reciprocity, and trust in humans, we found no evidence in favor of the hypotheses; nine main tests were preregistered, and all of them yielded small and statistically insignificant estimates. In secondary analyses, we used Bayesian inference and estimation to quantify support for our findings. Taken together, our results strongly suggest that the link between OPRM1 A118G variation and social-rejection sensitivity is weaker than previously thought.

  • 21.
    Popiolek, K.
    et al.
    Orebro Univ, Sweden.
    Beierot, S.
    Orebro Univ, Sweden.
    Brus, O.
    Orebro Univ, Sweden.
    Hammer, A.
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Leaden, M.
    Gothenburg Univ, Sweden; Karolinska Inst, Sweden.
    Lundberg, J.
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Nordanskog, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Nordenskjold, A.
    Orebro Univ, Sweden.
    Electroconvulsive therapy in bipolar depression - effectiveness and prognostic factors2019In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 140, no 3, p. 196-204Article in journal (Refereed)
    Abstract [en]

    Objective Electroconvulsive therapy (ECT) is used in patients with severe forms of bipolar depression. ECT is effective but not all patients respond. The aim of this study was to determine prognostic factors for response to ECT in patients hospitalized for bipolar depression. Methods Data were obtained from several national Swedish registers. All patients with bipolar depression treated with ECT in any hospital in Sweden between 2011 and 2016 for whom information about ECT response was available were included (n = 1251). Response was defined as a score on the Clinical Global Impression - Improvement scale of one or two. Univariate and multivariate logistic regression were conducted to investigate associations between socio-demographic and clinical factors and response. Results Response was achieved in 80.2% patients. Older age was associated with higher response rate to ECT. Patients with comorbid obsessive-compulsive disorder or personality disorder, and patients previously treated with lamotrigine had lower response rate. Conclusion Electroconvulsive therapy for bipolar depression was associated with very high response rates. The strongest prognostic factors were higher age, absence of comorbid obsessive-compulsive disorder or personality disorder, and less prior pharmacologic treatment.

  • 22.
    Rehm, Juergen
    et al.
    CAMH, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Tech Univ Dresden, Germany; IM Sechenov First Moscow State Med Univ, Russia.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Gual, Antoni
    Hosp Clin Barcelona, Spain; IDIBAPS Inst Recerca Biomed Agusti Pi and Sunyer, Spain; Inst Carlos III, Spain.
    ICD-11 for Alcohol Use Disorders: Not a Convincing Answer to the Challenges2019In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277Article in journal (Refereed)
    Abstract [en]

    n/a

  • 23.
    Rönnqvist, Ida
    et al.
    Orebro Univ, Sweden.
    Brus, Ole
    Orebro Univ, 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 Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Nordenskjold, Axel
    Orebro Univ, Sweden.
    Rehospitalization of Postpartum Depression and Psychosis After Electroconvulsive Therapy A Population-Based Study With a Matched Control Group2019In: Journal of ECT, ISSN 1095-0680, E-ISSN 1533-4112, Vol. 35, no 4, p. 264-271Article in journal (Refereed)
    Abstract [en]

    Objectives Electroconvulsive therapy (ECT) is used in some cases of postpartum depression (PPD) and postpartum psychosis (PPP). The risk of relapse for PPD and PPP after ECT is unknown. This study compared the relapse rate after ECT between women who had been treated for PPD and/or PPP and women who had been treated for depression and/or psychosis outside the postpartum period. Methods The Swedish National Quality Register for ECT and the Swedish National Patient Register were used to identify women with PPD and/or PPP who had been treated with ECT within 6 months after delivery. For each case, a control (treated with ECT but not postpartum) patient was also selected. A Kaplan-Meier estimator was used to calculate the relapse rate (defined as rehospitalization or suicide) after ECT. Cox regression was used to identify variables associated with relapse. Results A total of 180 patients were included in each group. The proportions of patients who suffered relapse after 6 months, 1 year, and 2 years were 28%, 31%, and 40% for the postpartum group and 39%, 50%, and 55% for the nonpostpartum group. Treatment with benzodiazepines, several previous psychiatric admissions, and the absence of improvement after ECT were associated with relapse. Conclusions The risk of relapse after ECT is lower for patients with PPD and/or PPP than for patients outside the postpartum period, but the risk is nonetheless substantial in both groups.

  • 24.
    Spagnolo, Primavera A.
    et al.
    NINDS, MD 20892 USA.
    Kimes, Alane
    NIDA, MD 20892 USA.
    Schwandt, Melanie L.
    NIAAA, MD 20892 USA.
    Shokri-Kojori, Ehsan
    NIAAA, MD 20892 USA.
    Thada, Shantalaxmi
    NIDA, MD 20892 USA.
    Phillips, Karran A.
    NIDA, MD 20892 USA.
    Diazgranados, Nancy
    NIAAA, MD 20892 USA.
    Preston, Kenzie L.
    NIDA, MD 20892 USA; NIDA, MD 20892 USA.
    Herscovitch, Peter
    NIDA, MD 20892 USA.
    Tomasi, Dardo
    NIAAA, MD 20892 USA.
    Ramchandani, Vijay A.
    NIAAA, MD 20892 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Striatal Dopamine Release in Response to Morphine: A [C-11]Raclopride Positron Emission Tomography Study in Healthy Men2019In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 86, no 5, p. 356-364Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preclinical and human positron emission tomography studies have produced inconsistent results regarding the effects of opioids on mesolimbic dopamine (DA). Here, we quantify striatal DA release (measured by [C-11]raclopride displacement) in response to an intravenous infusion of morphine, and its relationship with morphine-induced subjective effects, in healthy, nondependent opioid-experienced participants. METHODS: Fifteen healthy male participants were initially included. Sessions were on separate days. On session 1, participants received intravenous morphine (10 mg/70 kg) in the clinic to ensure tolerability. Participants without adverse reactions (n = 10) then received intravenous morphine and placebo (saline) sessions, in counterbalanced order, while undergoing [C-11]raclopride positron emission tomography scans. Subjective and physiological responses were assessed. Region-of-interest and voxelwise image analyses were used to assess changes in [C-11]raclopride nondisplaceable binding potential. RESULTS: Morphine produced marked subjective and physiological effects and induced a significant decrease in [C-11]raclopride nondisplaceable binding potential, particularly in the nucleus accumbens and globus pallidus, where the change in [C-11]raclopride nondisplaceable binding potential was approximately 9%. However, the subjective effects of morphine did not show a simple pattern of correlation with DA release. CONCLUSIONS: This is, to our knowledge, the first study providing in vivo human evidence that DA transmission in the ventral striatum is affected by morphine. Further studies are required to fully delineate the DA contribution to the reinforcing effects of opioids.

  • 25.
    Spagnolo, Primavera A.
    et al.
    Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
    Wang, Han
    Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Peking Union Medical College Hospital, Beijing, China.
    Srivanitchapoom, Prachaya
    Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Division of Neurology, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
    Schwandt, Melanie
    Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Hallett, Mark
    Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
    Lack of Target Engagement Following Low-Frequency Deep Transcranial Magnetic Stimulation of the Anterior Insula2019In: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 22, no 8, p. 877-883Article in journal (Refereed)
    Abstract [en]

    To evaluate the safety and efficacy of low-frequency, inhibitory, deep rTMS with a novel H-coil specifically designed to stimulate the insula.

  • 26.
    Zallar, L J
    et al.
    Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Bethesda, MD, USA; Neurobiology of Addiction Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Tunstall, B J
    Neurobiology of Addiction Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Richie, C T
    Genetic Engineering and Viral Vector Core, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Zhang, Y J
    Genetic Engineering and Viral Vector Core, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, Rockville, MD, USA.
    You, Z B
    Neuropsychopharmacology Section, Molecular Targets and Medications Discover Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Gardner, E L
    Neuropsychopharmacology Section, Molecular Targets and Medications Discover Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken. Not Found:Center for Social and Affective Neuroscience, IKE, Linköping University, Linköping, Sweden.
    Pickel, J
    Transgenic Core Facility, National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.
    Koob, G F
    Neurobiology of Addiction Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Vendruscolo, L F
    Neurobiology of Addiction Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Harvey, B K
    Molecular Mechanisms of Cellular Stress and Inflammation Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA.
    Leggio, L-
    Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Bethesda, MD, USA. lorenzo.leggio@nih.gov; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA.
    Development and initial characterization of a novel ghrelin receptor CRISPR/Cas9 knockout wistar rat model2019In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 43, no 2, p. 344-354Article in journal (Refereed)
    Abstract [en]

    Ghrelin, a stomach-derived hormone implicated in numerous behaviors including feeding, reward, stress, and addictive behaviors, acts by binding to the growth hormone secretagogue receptor (GHSR). Here, we present the development, verification, and initial characterization of a novel GHSR knockout (KO) Wistar rat model created with CRISPR genome editing.

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