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  • 1.
    Aho, Nikolas
    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.
    Proczkowska Björklund, Marie
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping. 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.
    Peritraumatic reactions in relation to trauma exposure and symptoms of posttraumatic stress in high school students2017In: European Journal of Psychotraumatology, ISSN 2000-8066, E-ISSN 2000-8066, Vol. 8, no 1, article id 1380998Article in journal (Refereed)
    Abstract [en]

    Background: Exposure to traumatic events is clearly associated with a diversity of subsequent mental health problems, with posttraumatic stress disorder (PTSD) as the most prevalent disorder. Epidemiologically, trauma exposure rates are more prevalent than PTSD, indicating that most trauma victims do not develop PTSD. More knowledge is needed to understand the development of the different posttraumatic pathways including the significance of pretraumatic, peritraumatic and posttraumatic risk factors. Objective: To study peritraumatic reactions in relation to trauma exposure and symptoms of posttraumatic stress and to enhance our understanding of peritraumatic reactions as mediators between trauma and later symptomatology. Method: The study was composed of a representative community sample of 5332 second year high school students (mean age 17.3 years) who completed the Juvenile Victimization Questionnaire (SAQ/JVQ), Trauma Symptom Checklist for Children (TSCC) and answered questions about peritraumatic reactions. Mediation effects of peritraumatic reactions on the trauma exposure relationship to symptoms was tested using the PROCESS macro for SPSS. Results: Traumatic events are common (84.1%) and are accompanied in three-quarters of the students with at least one form of peritraumatic reaction. Peritraumatic reactions, especially peritraumatic dissociative reactions, mediate the relationship between trauma exposure and symptoms, and gender moderates the effect of peritraumatic dissociation. This moderating effect was found to be larger for boys than for girls, indicating gender differences in response to trauma. Conclusions: The results indicate the need to screen for peritraumatic reactions as early as possible after a traumatic event in order to identify those at risk for PTSD.

  • 2.
    Aoun, E. G.
    et al.
    Brown Univ, RI 02912 USA.
    Jimenez, V. A.
    Oregon Hlth and Sci Univ, OR 97201 USA.
    Vendruscolo, L. F.
    Scripps Res Inst, CA 92037 USA; NIDA, MD 20892 USA.
    Walter, N. A. R.
    Oregon Hlth and Sci Univ, OR 97201 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.
    Ferrulli, A.
    Univ Cattolica Sacro Cuore, Italy.
    Haass-Koffler, C. L.
    Brown Univ, RI 02912 USA; NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Darakjian, P.
    Oregon Hlth and Sci Univ, OR 97201 USA.
    Lee, M. R.
    NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    Addolorato, G.
    Univ Cattolica Sacro Cuore, Italy.
    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, Department of Psychiatry.
    Hitzemann, R.
    Oregon Hlth and Sci Univ, OR 97201 USA.
    Koob, G. F.
    Scripps Res Inst, CA 92037 USA; NIAAA, MD 20852 USA.
    Grant, K. A.
    Oregon Hlth and Sci Univ, OR 97201 USA.
    Leggio, L.
    Brown Univ, RI 02912 USA; NIAAA, MD 20892 USA; NIDA, MD 20892 USA.
    A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans2018In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 6, p. 1466-1473Article in journal (Refereed)
    Abstract [en]

    Aldosterone regulates electrolyte and fluid homeostasis through binding to the mineralocorticoid receptors (MRs). Previous work provides evidence for a role of aldosterone in alcohol use disorders (AUDs). We tested the hypothesis that high functional activity of the mineralocorticoid endocrine pathway contributes to vulnerability for AUDs. In Study 1, we investigated the relationship between plasma aldosterone levels, ethanol self-administration and the expression of CYP11B2 and MR (NR3C2) genes in the prefrontal cortex area (PFC) and central nucleus of the amygdala (CeA) in monkeys. Aldosterone significantly increased after 6- and 12-month ethanol self-administration. NR3C2 expression in the CeA was negatively correlated to average ethanol intake during the 12 months. In Study 2, we measured Nr3c2 mRNA levels in the PFC and CeA of dependent and nondependent rats and the correlates with ethanol drinking during acute withdrawal. Low Nr3c2 expression levels in the CeA were significantly associated with increased anxiety-like behavior and compulsive-like drinking in dependent rats. In Study 3, the relationship between plasma aldosterone levels, alcohol drinking and craving was investigated in alcohol-dependent patients. Non-abstinent patients had significantly higher aldosterone levels than abstinent patients. Aldosterone levels positively correlated with the number of drinks consumed, craving and anxiety scores. These findings support a relationship between ethanol drinking and the aldosterone/MR pathway in three different species.

  • 3.
    Aronsson, Gunnar
    et al.
    University of Stockholm, Sweden.
    Theorell, Tores
    University of Stockholm, Sweden; Karolinska Institute, Sweden.
    Grape, Tom
    Health Care Centre, Sweden.
    Hammarstrom, Anne
    University of Umeå, Sweden.
    Högstedt, Christer
    Karolinska Institute, Sweden.
    Marteinsdottir, Ina
    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 Psychiatry.
    Skoog, Ingmar
    University of Gothenburg, Sweden.
    Traskman-Bendz, Lil
    Lund University, Sweden.
    Hall, Charlotte
    Swedish Council Health Technology Assessment, Sweden.
    A systematic review including meta-analysis of work environment and burnout symptoms2017In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 17, article id 264Article, review/survey (Refereed)
    Abstract [en]

    Background: Practitioners and decision makers in the medical and insurance systems need knowledge on the relationship between work exposures and burnout. Many burnout studies -original as well as reviews-restricted their analyses to emotional exhaustion or did not report results on cynicism, personal accomplishment or global burnout. To meet this need we carried out this review and meta-analyses with the aim to provide systematically graded evidence for associations between working conditions and near-future development of burnout symptoms. Methods: A wide range of work exposure factors was screened. Inclusion criteria were: 1) Study performed in Europe, North America, Australia and New Zealand 1990-2013. 2) Prospective or comparable case control design. 3) Assessments of exposure (work) and outcome at baseline and at least once again during follow up 1-5 years later. Twenty-five articles met the predefined relevance and quality criteria. The GRADE-system with its 4-grade evidence scale was used. Results: Most of the 25 studies focused emotional exhaustion, fewer cynicism and still fewer personal accomplishment. Moderately strong evidence (grade 3) was concluded for the association between job control and reduced emotional exhaustion and between low workplace support and increased emotional exhaustion. Limited evidence (grade 2) was found for the associations between workplace justice, demands, high work load, low reward, low supervisor support, low co-worker support, job insecurity and change in emotional exhaustion. Cynicism was associated with most of these work factors. Reduced personal accomplishment was only associated with low reward. There were few prospective studies with sufficient quality on adverse chemical, biological and physical factors and burnout. Conclusion: While high levels of job support and workplace justice were protective for emotional exhaustion, high demands, low job control, high work load, low reward and job insecurity increased the risk for developing exhaustion. Our approach with a wide range of work exposure factors analysed in relation to the separate dimensions of burnout expanded the knowledge of associations, evidence as well as research needs. The potential of organizational interventions is illustrated by the findings that burnout symptoms are strongly influenced by structural factors such as job demands, support and the possibility to exert control.

  • 4.
    Augier, Eric
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Barbier, Estelle
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Dulman, Russell S
    Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois, Chicago, IL 60612, USA.
    Licheri, Valentina
    Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Göteborg, 413 90 Göteborg, Sweden.
    Augier, Gaëlle
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Domi, Esi
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Barchiesi, Riccardo
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Farris, Sean
    The Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX 78712, USA.
    Nätt, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Mayfield, R Dayne
    The Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX 78712, USA.
    Adermark, Louise
    Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Göteborg, 413 90 Göteborg, 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, Department of Psychiatry.
    A molecular mechanism for choosing alcohol over an alternative reward.2018In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 360, no 6395, p. 1321-1326Article in journal (Refereed)
    Abstract [en]

    Alcohol addiction leads to increased choice of alcohol over healthy rewards. We established an exclusive choice procedure in which ~15% of outbred rats chose alcohol over a high-value reward. These animals displayed addiction-like traits, including high motivation to obtain alcohol and pursuit of this drug despite adverse consequences. Expression of the γ-aminobutyric acid (GABA) transporter GAT-3 was selectively decreased within the amygdala of alcohol-choosing rats, whereas a knockdown of this transcript reversed choice preference of rats that originally chose a sweet solution over alcohol. GAT-3 expression was selectively decreased in the central amygdala of alcohol-dependent people compared to those who died of unrelated causes. Impaired GABA clearance within the amygdala contributes to alcohol addiction, appears to translate between species, and may offer targets for new pharmacotherapies for treating this disorder.

  • 5.
    Augier, Eric
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Dulman, Russell S.
    NIAAA, MD USA.
    Damadzic, Ruslan
    NIAAA, MD USA.
    Pilling, Andrew
    NIAAA, MD USA.
    Hamilton, Paul
    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, Department of Psychiatry.
    The GABA(B) Positive Allosteric Modulator ADX71441 Attenuates Alcohol Self-Administration and Relapse to Alcohol Seeking in Rats2017In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 42, no 9, p. 1789-1799Article in journal (Refereed)
    Abstract [en]

    GABAergic signaling is involved in modulating the reinforcing properties of alcohol, and GABA(B) receptors have been proposed as a potential target for clinical treatment of alcoholism. The orthosteric GABA(B) receptor agonist baclofen has been shown to suppress operant self-administration of alcohol in animals and alcohol use in alcohol-dependent patients, but its utility is limited by a narrow therapeutic index. We tested the effects of ADX71441, a novel GABA(B) receptor positive allosteric modulator, on alcohol-related behaviors in rats. We first assessed the effects of ADX71441 ( 1, 3, 10 and 30 mg/kg, I.P.) on both non-dependent and dependent male Wistar rats trained to self-administer 20% alcohol. We then determined the effects of ADX71441 on stress-induced as well as cue-induced relapse-like behavior. Finally, we sought to identify the brain regions through which ADX71441 may act to prevent relapse-like behavior by mapping the neuronal activation induced by stress-induced reinstatement of alcohol-seeking using c-Fos immunohistochemistry. ADX71441 dose-dependently decreased alcohol self-administration of both dependent and non-dependent animals, but its potency was higher in alcohol-dependent rats. Furthermore, both cue-and stress-induced alcohol seeking were blocked by the GABA(B) receptor positive allosteric modulator. Finally, pretreatment with 3 mg/kg of ADX71441 before stress-induced reinstatement significantly decreased c-Fos expression in a network of brain regions implicated in stress-induced relapse, comprising the nucleus accumbens shell, the dorsal raphe nucleus and the medial prefrontal cortex. Our findings support a causal role of GABAB receptors in alcohol reinforcement and relapse to alcohol seeking. These effects are observed in the absence of significant sedative side effects. Jointly, these observations indicate that GABAB receptor positive allosteric modulators merit being tested clinically for the treatment of alcoholism. Our data also point to a potential biomarker of target engagement for early clinical studies.

  • 6.
    Augier, Eric
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Dulman, Russell S.
    National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA.
    Singley, Erick
    National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 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, Department of Psychiatry.
    A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training2017In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 119, article id e53305Article in journal (Refereed)
    Abstract [en]

    Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods require saccharin/sucrose fading, water deprivation and/or extended training to initiate operant responding in rats. This paper describes a novel and efficient method to quickly initiate operant responding for ethanol that is convenient for experimenters and does not require water deprivation or saccharin/sucrose fading, thus eliminating the potential confound of using sweeteners in ethanol operant self-administration studies. With this method, Wistar rats typically acquire and maintain self-administration of a 20% ethanol solution in less than two weeks of training. Furthermore, blood ethanol concentrations and rewards are positively correlated for a 30 min self-administration session. Moreover, naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress ethanol self-administration in rodents, dose-dependently decreases alcohol intake and motivation to consume alcohol for rats self-administering 20% ethanol, thus validating the use of this new method to study the reinforcing properties of alcohol in rats.

  • 7.
    Aziz, Abdul Maruf Asif
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Neuropeptide Receptors as Treatment Targets in Alcohol Use Disorders2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Alcohol use disorder (AUD) is a complex disorder with multiple pathophysiological processes contributing to the initiation, progression and development of the disease state. AUD is a chronic relapsing disease with escalation of alcohol-intake over time in repeated cycles of tolerance, abstinence and relapse and hence, it is very difficult to treat. There are only a few currently available treatments with narrow efficacy and variable patient response. Thus it is important to find new, more effective medications to increase the number of patients who can benefit from pharmacological treatment of AUD.

    The research presented in this thesis work focuses on the critical involvement of central neuropeptides in alcohol-related behaviors. The overall aim was to evaluate the nociceptin/orphanin FQ (NOP) receptor, the neuropeptide Y (NPY) Y2 receptor and the melanin-concentrating hormone (MCH) receptor 1 as novel and potential pharmacological treatment targets for AUD by testing the NOP receptor agonist SR-8993, the NPY-Y2 receptor antagonist CYM-9840 and the MCH1 receptor antagonist GW803430 in established animal models.

    In the first study (Paper I), the novel and selective NOP agonist SR-8993 was assessed in rat models of motivation to obtain alcohol and relapse to alcohol seeking behavior using the operant self-administration (SA) paradigm. Firstly, treatment with SR-8993 (1 mg/kg) showed a mildly anxiolytic effect and reversed acute alcohol withdrawal-induced “hangover” anxiety in the elevated plus-maze (EPM). Next, it potently attenuated alcohol SA and motivation to obtain alcohol in the progressive ratio responding (PRR) and reduced both alcohol cue-induced and yohimbine stress-induced reinstatement of alcohol seeking, without affecting the pharmacology and metabolism of alcohol nor other control behaviors. To extend these findings, SR-8993 was evaluated in escalated alcohol-intake in rats.  Treatment with SR-8993 significantly suppressed alcohol-intake and preference in rats that were trained to consume high amounts of alcohol in the two-bottle free choice intermittent access (IA) paradigm. SR-8993 also blocked operant SA of alcohol in rats that showed robust escalation in operant alcohol SA following chronic IA exposure to alcohol.

    In the second study (Paper II), SR-8993 was further evaluated in a model for escalated alcohol-intake induced by long-term IA exposure to alcohol. The effect of previous experience on operant alcohol SA on two-bottle free choice preference drinking was evaluated and sensitivity to treatment with SR-8993 was tested in rats selected for escalated and non-escalated alcohol seeking behavior. We found that rats exposed to the combined SA-IA paradigm showed greater sensitivity to SR-8993 treatment. In addition, acute escalation of alcohol SA after a three-week period of abstinence was completely abolished by pretreatment with SR-8993.

    In the third study (Paper III), the effects of the novel, small molecule NPY-Y2 antagonist CYM-9840 were tested in operant alcohol SA, PRR which is a model for motivation to work for alcohol and reinstatement of alcohol-seeking behavior. Treatment with CYM-9840 (10 mg/kg) potently attenuated alcohol SA, progressive ratio responding and stress-induced reinstatement using yohimbine as the stressor, while alcohol cue-induced reinstatement was unaffected. Moreover, a range of control behaviors including taste sensitivity, locomotor and pharmacological sensitivity to the sedative effects of alcohol remained unaffected by CYM-9840 pretreatment, indicating that its effects are specific to the rewarding and motivational aspects of alcohol-intake and related behaviors. CYM-9840 also reversed acute alcohol withdrawal-induced “hangover” anxiety measured in the EPM and reduced alcohol-intake in the 4 hour limited access two-bottle free choice preference drinking model.

    Finally, in the fourth study (Paper IV), the selective MCH1-R antagonist GW803430 was tested in rat models of escalated alcohol-intake. Pretreatment with GW803430 (effective at 10 & 30 mg/kg) dose-dependently reduced alcohol and food-intake in rats that consumed high amounts of alcohol during IA, while it only decreased food-intake in rats that consumed low amounts of alcohol during IA, likely due to a floor effect. Upon protracted abstinence following IA, GW803430 significantly reduced operant alcohol SA and this was associated with adaptations in MCH and MCH1-R gene-expression. In contrast, GW803430 did not affect escalated alcohol SA induced by chronic alcohol vapor exposure and this was accompanied by no change in MCH or MCH1-R gene expression. Overall, these results suggest that the MCH1-R antagonist affects alcohol-intake through regulation of both motivation for caloric-intake and the rewarding properties of alcohol.

    In conclusion, our results suggest critical roles for these central neuropeptides in the regulation of anxiety and of alcohol reward, making them potential pharmacological targets in the treatment of AUD.

    List of papers
    1. The nociceptin/orphanin FQ receptor agonist SR-8993 as a candidate therapeutic for alcohol use disorders: validation in rat models
    Open this publication in new window or tab >>The nociceptin/orphanin FQ receptor agonist SR-8993 as a candidate therapeutic for alcohol use disorders: validation in rat models
    Show others...
    2016 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 19-20, p. 3553-3563Article in journal (Refereed) Published
    Abstract [en]

    RATIONALE: Alcoholism is a complex disorder in which diverse pathophysiological processes contribute to initiation and progression, resulting in a high degree of heterogeneity among patients. Few pharmacotherapies are presently available, and patient responses to these are variable. The nociceptin/orphanin FQ (NOP) receptor has been suggested to play a role both in alcohol reward and in negatively reinforced alcohol seeking. Previous studies have shown that NOP-receptor activation reduces alcohol intake in genetically selected alcohol-preferring as well as alcohol-dependent rats. NOP activation also blocks stress- and cue-induced reinstatement of alcohol-seeking behavior.

    OBJECTIVES: Here, we aimed to examine a novel, potent, and brain-penetrant small-molecule NOP-receptor agonist, SR-8993, in animal models of alcohol- as well as anxiety-related behavior using male Wistar rats.

    RESULTS: SR-8993 was mildly anxiolytic when given to naïve animals and potently reversed acute alcohol withdrawal-induced ("hangover") anxiety. SR-8993 reduced both home-cage limited access drinking, operant responding for alcohol, and escalation induced through prolonged intermittent access to alcohol. SR-8993 further attenuated stress- as well as cue-induced relapse to alcohol seeking. For the effective dose (1.0 mg/kg), non-specific effects such as sedation may be limited, since a range of control behaviors were unaffected, and this dose did not interact with alcohol elimination.

    CONCLUSION: These findings provide further support for NOP-receptor agonism as a promising candidate treatment for alcoholism and establish SR-8993 or related molecules as suitable for further development as therapeutics.

    Place, publisher, year, edition, pages
    Springer, 2016
    Keywords
    Nociception/orphanin FQ, Agonist, Wistar rat, Alcohol, Operant, Reinstatement, Elevated plus-maze
    National Category
    Substance Abuse
    Identifiers
    urn:nbn:se:liu:diva-132347 (URN)10.1007/s00213-016-4385-8 (DOI)000383672500006 ()27515665 (PubMedID)
    Note

    Funding Agencies|National Institutes of Health [R01-DA035055]; Swedish Research Council [2010-3219]

    Available from: 2016-11-12 Created: 2016-11-01 Last updated: 2017-08-21Bibliographically approved
    2. Melanin-Concentrating Hormone and Its MCH-1 Receptor: Relationship Between Effects on Alcohol and Caloric Intake
    Open this publication in new window or tab >>Melanin-Concentrating Hormone and Its MCH-1 Receptor: Relationship Between Effects on Alcohol and Caloric Intake
    Show others...
    2016 (English)In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 40, no 10, p. 2199-2207Article in journal (Refereed) Published
    Abstract [en]

    Background: Reward and energy homeostasis are both regulated by a network of hypothalamic neuropeptide systems. The melanin-concentrating hormone (MCH) and its MCH-1 receptor (MCH1-R) modulate alcohol intake, but it remains unknown to what extent this reflects actions on energy balance or reward. Here, we evaluated the MCH1-R in regulation of caloric intake and motivation to consume alcohol in states of escalated consumption.

    Methods: Rats had intermittent access (IA) to alcohol and were divided into high- and low-drinking groups. Food and alcohol consumption was assessed after administration of an MCH1-R antagonist, GW803430. Next, GW803430 was evaluated on alcohol self-administration in protracted abstinence induced by IA in high-drinking rats. Finally, the effect of GW803430 was assessed on alcohol self-administration in acute withdrawal in rats exposed to alcohol vapor. Gene expression of MCH and MCH1-R was measured in the hypothalamus and nucleus accumbens (NAc) in both acute and protracted abstinence.

    Results: High-drinking IA rats consumed more calories from alcohol than chow and GW803430 decreased both chow and alcohol intake. In low-drinking rats, only food intake was affected. In protracted abstinence from IA, alcohol self-administration was significantly reduced by pretreatment with GW803430 and gene expression of both MCH and the MCH1-R were dysregulated in hypothalamus and NAc. In contrast, during acute withdrawal from vapor exposure, treatment with GW803430 did not affect alcohol self-administration, and no changes in MCH or MCH1-R gene expression were observed.

    Conclusions: Our data suggest a dual role of MCH and the MCH1-R in regulation of alcohol intake, possibly through mechanisms involving caloric intake and reward motivation. A selective suppression of alcohol self-administration during protracted abstinence by GW803430 was observed and accompanied by adaptations in gene expression of MCH and MCH1-R. Selective suppression of escalated consumption renders the MCH1-R an attractive target for treatment of alcohol use disorders.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2016
    Keywords
    Alcohol Escalation, Reward, Motivation, Calorie Intake, Melanin-Concentrating Hormone Receptor-1
    National Category
    Substance Abuse
    Identifiers
    urn:nbn:se:liu:diva-132522 (URN)10.1111/acer.13181 (DOI)000385542900017 ()27579857 (PubMedID)
    Available from: 2016-11-14 Created: 2016-11-13 Last updated: 2018-03-19Bibliographically approved
  • 8.
    Badiani, Aldo
    et al.
    Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy; Sussex Addiction Research and Intervention Centre (SARIC), University of Sussex, Brighton, UK.
    Berridge, Kent C.
    Department of Psychology, University of Michigan, Ann Arbor, MI, 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, Department of Psychiatry.
    Nutt, David J.
    Imperial College, London, UK.
    Robinson, Terry E.
    Department of Psychology, University of Michigan, Ann Arbor, MI, USA.
    Comments: Addiction research and theory: a commentary on the Surgeon Generals Report on alcohol, drugs, and health2018In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, Vol. 23, no 1, p. 3-5Article in journal (Other academic)
    Abstract [en]

    The Office of the Surgeon General recently produced its first Report on the consequences of alcohol and drug abuse on health, making several very laudable policy recommendations. The Report also emphasizes the importance of adequate funding for biomedical research, which is good news for both researchers and patients. However, the Report is marred by a biased viewpoint on the psychology and neurobiology of drug addiction. We highlight here four controversial issues that were depicted as facts in the Report, thereby potentially misleading non-expert readers about the current state-of-the-art understanding of the psychology and neurobiology of drug addiction. It will be important to recognize a fuller range of scientific viewpoints in addiction neuroscience to avoid amplifying this bias in the coming years.

  • 9.
    Baker, Maggie
    et al.
    NIAAA, USA.
    Lindell, Stephen G.
    NIAAA, USA.
    Driscoll, Carlos A.
    NIAAA, USA.
    Zhou, Zhifeng
    NIAAA, USA.
    Yuan, Qiaoping
    NIAAA, USA.
    Schwandt, Melanie L.
    NIAAA, USA.
    Miller-Crews, Isaac
    NIAAA, USA.
    Simpson, Elizabeth A.
    Eunice Shriver Kennedy National Institute Child Health and Huma, MD 20837 USA.
    Paukner, Annika
    Eunice Shriver Kennedy National Institute Child Health and Huma, MD 20837 USA.
    Francesco Ferrari, Pier
    University of Claude Bernard Lyon, France.
    Kumar Sindhu, Ravi
    NIAAA, MD 20852 USA.
    Razaqyar, Muslima
    NIAAA, USA.
    Sommer, Wolfgang H.
    Heidelberg University, Germany; Heidelberg University, Germany.
    Lopez, Juan F.
    University of Michigan, MI 48109 USA.
    Thompson, Robert C.
    University of Michigan, MI 48109 USA.
    Goldman, David
    NIAAA, 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, Department of Psychiatry.
    Dee Higley, J.
    Brigham Young University, UT 84602 USA.
    Suomi, Stephen J.
    Eunice Shriver Kennedy National Institute Child Health and Huma, MD 20837 USA.
    Barr, Christina S.
    NIAAA, USA.
    Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 44, p. 11769-11774Article in journal (Refereed)
    Abstract [en]

    Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to deter mine whether a gain-of-function nonsynonymous OXTR SNP inter acted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavior al differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.

  • 10.
    Barbier, Estelle
    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, Department of Psychiatry.
    mTORC and ProSAPiP1: How Alcohol Changes Synapses of Reward Circuitry2017In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 96, no 1Article in journal (Other academic)
    Abstract [en]

    Alcohol addiction is characterized by broad and persistent changes in brain function, but the underlying neural adaptations remain largely unknown. In this issue of Neuron, Laguesse et al. (2017) describe a neural mechanism through which long-term alcohol exposure induces structural and synaptic adaptations that promote excessive alcohol use.

  • 11.
    Barbier, Estelle
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Johnstone, A. L.
    University of Miami, FL 33136 USA.
    Khomtchouk, B. B.
    University of Miami, FL 33136 USA.
    Tapocik, J. D.
    NIAAA, MD USA.
    Pitcairn, C.
    NIAAA, MD USA.
    Rehman, F.
    NIAAA, MD USA.
    Augier, Eric
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Borich, A.
    NIAAA, MD USA.
    Schank, J. R.
    University of Georgia, GA 30602 USA.
    Rienas, C. A.
    University of Miami, FL 33136 USA.
    Van Booven, D. J.
    University of Miami, FL 33136 USA.
    Sun, H.
    NIAAA, MD USA.
    Nätt, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Wahlestedt, C.
    University of Miami, FL 33136 USA; University of Miami, FL 33136 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, Department of Psychiatry. NIAAA, MD USA.
    Dependence-induced increase of alcohol self-administration and compulsive drinking mediated by the histone methyltransferase PRDM22017In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 22, no 12, p. 1746-1758Article in journal (Refereed)
    Abstract [en]

    Epigenetic processes have been implicated in the pathophysiology of alcohol dependence, but the specific molecular mechanisms mediating dependence-induced neuroadaptations remain largely unknown. Here, we found that a history of alcohol dependence persistently decreased the expression of Prdm2, a histone methyltransferase that monomethylates histone 3 at the lysine 9 residue (H3K9me1), in the rat dorsomedial prefrontal cortex (dmPFC). Downregulation of Prdm2 was associated with decreased H3K9me1, supporting that changes in Prdm2 mRNA levels affected its activity. Chromatin immunoprecipitation followed by massively parallel DNA sequencing showed that genes involved in synaptic communication are epigenetically regulated by H3K9me1 in dependent rats. In non-dependent rats, viral-vector-mediated knockdown of Prdm2 in the dmPFC resulted in expression changes similar to those observed following a history of alcohol dependence. Prdm2 knockdown resulted in increased alcohol self-administration, increased aversion-resistant alcohol intake and enhanced stress-induced relapse to alcohol seeking, a phenocopy of postdependent rats. Collectively, these results identify a novel epigenetic mechanism that contributes to the development of alcohol-seeking behavior following a history of dependence.

  • 12.
    Bejerot, Susanne
    et al.
    Karolinska Institutet, Clinical Neuroscience Stockholm, Sweden .
    Landén, Mikael
    Göteborgs universitet, Sahlgrenska akademin, 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, Department of Psychiatry.
    Anckarsäter, Henrik
    Göteborgs universitet, Sahlgrenska akademin, Sweden.
    Waern, Magda
    Göteborgs universitet, Sahlgrenska akademin, Sweden.
    Socialstyrelsens målnivåer signalerar brist på tillit in Lakartidningen, vol 114, issue , pp2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article in journal (Other academic)
  • 13.
    Bendas, Johanna
    et al.
    Technical University of Dresden, Germany.
    Georgiadis, Janniko R.
    University of Medical Centre Groningen, Netherlands.
    Ritschel, Gerhard
    Technical University of Dresden, Germany.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Weidner, Kerstin
    Technical University of Dresden, Germany.
    Croy, Ilona
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Technical University of Dresden, Germany.
    C-Tactile Mediated Erotic Touch Perception Relates to Sexual Desire and Performance in a Gender-Specific Way2017In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 14, no 5, p. 645-653Article in journal (Refereed)
    Abstract [en]

    Background: Unmyelinated low-threshold mechanoreceptors-the so-called C-tactile (CT) afferents-play a crucial role in the perception and conduction of caressing and pleasant touch sensations and significantly contribute to the concept of erotic touch perception. Aim: To investigate the relations between sexual desire and sexual performance and the perception of touch mediated by CT afferents. Methods: Seventy healthy participants (28 men, 42 women; mean age+/-SD = 24.84+/-4.08 years, range = 18-36 years) underwent standardized and highly controlled stroking stimulation that varied in the amount of CT fiber stimulation by changing stroking velocity (CT optimal = 1, 3 and 10 cm/s; CT suboptimal = 0.1, 0.3, and 30 cm/s). Participants rated the perceived pleasantness, eroticism, and intensity of the applied tactile stimulation on a visual analog scale, completed the Sexual Desire Inventory, and answered questions about sexual performance. Outcomes: Ratings of perceived eroticism of touch were related to self-report levels of sexual desire and sexual performance. Results: Pleasantness and eroticism ratings showed similar dependence on stroking velocity that aligned with the activity of CT afferents. Erotic touch perception was related to sexual desire and sexual performance in a gender-specific way. In women, differences in eroticism ratings between CT optimal and suboptimal velocities correlated positively with desire for sexual interaction. In contrast, in men, this difference correlated to a decreased frequency and longer duration of partnered sexual activities. Clinical Implications: The present results lay the foundation for future research assessing these relations in patients with specific impairments of sexual functioning (eg, hypoactive sexual desire disorder). Strengths and Limitations: The strength of the study is the combination of standardized neurophysiologic methods and behavioral data. A clear limitation of the study design is the exclusion of exact data on the female menstrual cycle and the recruitment of an inhomogeneous sample concerning sexual orientation. Conclusion: The present results provide further evidence that unmyelinated CT afferents play a role in the complex mechanism of erotic touch perception. The ability to differentiate between CT optimal and suboptimal stimuli relates to sexual desire and performance in a gender-specific way. Copyright (C) 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  • 14.
    Bergamino, Maurizio
    et al.
    Laureate Institute for Brain Research, Tulsa, OK, USA.
    Farmer, Madison
    Roosevelt University, Department of Industrial and Organizational Psychology, Chicago, IL, USA.
    Yeh, Hung-Wen
    Laureate Institute for Brain Research, Tulsa, OK, USA.
    Paul, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Statistical differences in the white matter tracts in subjects with depression by using different skeletonized voxel-wise analysis approaches and DTI fitting procedures2017In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1669, p. 131-140Article in journal (Refereed)
    Abstract [en]

    Major depressive disorder (MDD) is one of the most significant contributors to the global burden of illness. Diffusion tensor imaging (DTI) is a procedure that has been used in several studies to characterize abnormalities in white matter (WM) microstructural integrity in MDD. These studies, however, have provided divergent findings, potentially due to the large variety of methodological alternatives available in conducting DTI research. In order to determine the importance of different approaches to coregistration of DTI-derived metrics to a standard space, we compared results from two different skeletonized voxel-wise analysis approaches: the standard TBBS pipeline and the Advanced Normalization Tools (ANTs) approach incorporating a symmetric image normalization (SyN) algorithm and a group-wise template (ANTs TBSS). We also assessed effects of applying twelve different fitting procedures for the diffusion tensor. For our dataset, lower fractional anisotropy (FA) and axial diffusivity (AD) in depressed subjects compared with healthy controls were found for both methods and for all fitting procedures. No group differences were found for radial and mean diffusivity indices. Importantly, for the AD metric, the normalization methods and fitting procedures showed reliable differences, both in the volume and in the number of significant between-groups difference clusters detected. Additionally, a significant voxel-based correlation, in the left inferior fronto-occipital fasciculus, between AD and self-reported stress was found only for one of the normalization procedure (ANTs TBSS). In conclusion, the sensitivity to detect group-level effects on DTI metrics might depend on the DTI normalization and/or tensor fitting procedures used.

  • 15.
    Björnsdotter Åberg, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Davidovic, Monika
    Univ Gothenburg, Sweden.
    Karjalainen, Louise
    Univ Gothenburg, Sweden.
    Starck, Goran
    Univ Gothenburg, Sweden.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Gothenburg, Sweden.
    Wentz, Elisabet
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Grey matter correlates of autistic traits in women with anorexia nervosa2018In: Journal of Psychiatry & Neuroscience, ISSN 1180-4882, E-ISSN 1488-2434, Vol. 43, no 2, p. 79-86Article in journal (Refereed)
    Abstract [en]

    Background: Patients with anorexia nervosa exhibit higher levels of behaviours typically associated with autism-spectrum disorder (ASD), but the neural basis is unclear. We sought to determine whether elevated autistic traits in women with anorexia nervosa may be reflected in cortical morphology. Methods: We used voxel-based morphometry (VBM) to examine regional grey matter volumes in high-resolution MRI structural brain scans in women with anorexia nervosa and matched healthy controls. The Autism-spectrum Quotient (AQ) scale was used to assess autistic traits. Results: Women with anorexia nervosa (n = 25) had higher AQ scores and lower bilateral superior temporal sulcus (STS) grey matter volumes than the control group (n = 25). The AQ scores correlated negatively with average left STS grey matter volume in women with anorexia nervosa. Limitations: We did not control for cognitive ability and examined only women with ongoing anorexia nervosa. Conclusion: Elevated autistic traits in women with anorexia nervosa are associated with morphometric alterations of brain areas linked to social cognition. This finding provides neurobiological support for the behavioural link between anorexia nervosa and ASD and emphasizes the importance of recognizing autistic traits in preventing and treating-anorexia nervosa.

  • 16.
    Blomqvist, Anders
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Neural Mechanisms of Inflammation-Induced Fever2018In: The Neuroscientist, ISSN 1073-8584, E-ISSN 1089-4098, Vol. 24, no 4, p. 381-399Article, review/survey (Refereed)
    Abstract [en]

    Fever is a common symptom of infectious and inflammatory disease. It is well-established that prostaglandin E-2 is the final mediator of fever, which by binding to its EP3 receptor subtype in the preoptic hypothalamus initiates thermogenesis. Here, we review the different hypotheses on how the presence of peripherally released pyrogenic substances can be signaled to the brain to elicit fever. We conclude that there is unequivocal evidence for a humoral signaling pathway by which proinflammatory cytokines, through their binding to receptors on brain endothelial cells, evoke fever by eliciting prostaglandin E-2 synthesis in these cells. The evidence for a role for other signaling routes for fever, such as signaling via circumventricular organs and peripheral nerves, as well as transfer into the brain of peripherally synthesized prostaglandin E-2 are yet far from conclusive. We also review the efferent limb of the pyrogenic pathways. We conclude that it is well established that prostaglandin E-2 binding in the preoptic hypothalamus produces fever by disinhibition of presympathetic neurons in the brain stem, but there is yet little understanding of the mechanisms by which factors such as nutritional status and ambient temperature shape the response to the peripheral immune challenge.

  • 17.
    Bouwmeester, S
    et al.
    Erasmus University, The Netherlands.
    Verkoeijen, P. P. J. L.
    Erasmus University, The Netherlands.
    Aczel, B
    Eotvos Lorand University, Hungary.
    Barbosa, F
    University of Porto, Portugal.
    Bègue, L
    Universite Grenoble Alpes, France.
    Brañas-Garza, P
    Middlesex University, UK.
    Chmura, TGH
    University of Nottingham, UK.
    Cornelissen, G
    Pompeu Fabra University, Barcelona, Spain.
    Døssing, FS
    University of Copenhagen, Denmark.
    Espín, AM
    Middlesex University, UK.
    Evans, AM
    Tilburg University, The Netherlands.
    Ferreira-Santos, S
    University of Porto, Portugal.
    Fiedler, S
    Max Planck Institute, Germany.
    Flegr, J
    Charles University, Prague, Czech Republic.
    Ghaffari, M
    Max Planck Institute, Germany.
    Glöckner, A
    University of Hagen, Germany; Max Planck Institute, Germany.
    Goeschl, T
    University of Heidelberg, Germany.
    Guo, L
    University of California, USA.
    Hauser, OP
    Harvard University, USA.
    Hernan-Gonzalez, R
    University of Nottingham, UK.
    Herrero, A
    Universite Grenoble Alpes, France.
    Horne, Z
    University of Illinois, USA.
    Houdek, P
    University of Economics, Prague, Czech Republic.
    Johannesson, M
    Stockholm University, Sweden.
    Koppel, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Kujal, P
    Middlesex University, UK.
    Laine, T
    Universite Grenoble Alpes, France.
    Lohse, J
    University of Birmingham, UK.
    Martins, EC
    Maia University, Institute ISMI/CPUP, USA.
    Mauro, C
    Catholic University of Portugal, Portugal.
    Mischkowski, D
    University of Hagen, Germany.
    Mukherjee, S
    Indian Institute of Management Ahmedabad, India.
    Myrseth, KOR
    Trinity College Dublin, Ireland.
    Navarro-Martínez, D
    Pompeu Fabra University, Barcelona, Spain.
    Neal, TMS
    Arizona State University, USA.
    Novakova, J
    Charles University, Prague, Czech Republic.
    Pagà, R
    Pompeu Fabra University, Barcelona, Spain.
    Paiva, TO
    University of Porto, Portugal.
    Palfi, B
    Eotvos Lorand University, Hungary.
    Piovesan, M
    University of Copenhagen, Denmark.
    Rahal, RM
    Max Planck Institute, Germany.
    Salomon, E
    University of Illinois, USA.
    Srinivasan, N
    University of Allahabad, India.
    Srivastava, A
    University of Allahabad, India.
    Szaszi, B
    Eotvos Lorand University, Hungary.
    Szollosi, A
    Eotvos Lorand University, Hungary.
    Thor, K Ø
    University of Copenhagen, Denmark.
    Tinghög, Gustav
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Trueblood, JS
    Vanderbilt University, USA.
    van Bavel, JJ
    New York University, USA.
    van ‘t Veer, A. E.
    Leiden University, The Netherlands.
    Västfjäll, Daniel
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Decision Research, Eugene, OR, USA.
    Warner, M
    Arizona State University, USA.
    Wengström, E
    Lund University, Sweden.
    Wills, J
    New York University, USA.
    Wollbrant, CE
    University of Gothenburg, Sweden; NTNU Business School, Norway.
    Registered Replication Report: Rand, Greene, and Nowak (2012): Multilab direct replication of: Study 7 from Rand, D. G., Greene, J. D., & Nowak, M. A. (2012) Spontaneous giving and calculated greed. Nature, 489, 427–430.2017In: Perspectives on Psychological Science, ISSN 1745-6916, E-ISSN 1745-6924, Vol. 12, no 3, p. 527-542Article in journal (Refereed)
    Abstract [en]

    In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of −0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation. 

  • 18.
    Brus, O.
    et al.
    Örebro University, Sweden.
    Cao, Y.
    Örebro University, Sweden; Karolinska Institute, Sweden.
    Gustafsson, E.
    Umeå University Hospital, Sweden.
    Hulten, M.
    Lund University, Sweden.
    Landen, M.
    Karolinska Institute, Sweden; Gothenburg University, Sweden.
    Lundberg, J.
    Karolinska Institute, Sweden; Stockholm County 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, Department of Psychiatry.
    Nordenskjold, A.
    Örebro University, Sweden.
    Self-assessed remission rates after electroconvulsive therapy of depressive disorders2017In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 45, p. 154-160Article in journal (Refereed)
    Abstract [en]

    Background: Electroconvulsive therapy (ECT) effectively treats severe depression, but not all patients remit. The aim of the study was to identify clinical factors that associate with ECT-induced remission in a community setting. Methods: Depressed patients who underwent ECT in 2011-2014 were identified from the Swedish National Quality Register for ECT. Remission was defined as self-rated Montgomery-Asberg Depression Rating Scale scores of 0-10 after ECT. Other registers provided data on previous antidepressant use, comorbidities, and demographics. Results: Of 1671 patients fulfilling the inclusion criteria, 42.8% achieved remission. Older age, education length over 9 years, psychotic symptoms, shorter duration of preceding antidepressant use, pulse width stimulus amp;gt;= 0.50 ms, absence of substance use disorders, anxiety diagnosis, lamotrigine, and benzodiazepines, were associated with remission. Conclusions: This study shows that psychotic subtype of depression and older age are clinically relevant predictors of a beneficial ECT effect. Additionally, ECT outcomes can be further improved by optimizing the treatment technique and concomitant medication. (C) 2017 The Author(s). Published by Elsevier Masson SAS.

  • 19.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of 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 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 Psychiatry.
    Hoffmann, Mikael
    Stiftelsen NEPI - nätverk för läkmedelsepidemiologi - Linköping, Sweden .
    Dynamiken i förskrivningen av opioider i Sverige 2000–2015 - Markanta omfördelningar inom opioidgruppen, men ingen »epidemi«2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article in journal (Refereed)
    Abstract [en]

    Opioid prescription changes in Sweden 2000-2015 In contrast to the well-established »opioid epidemic« in the US, very little is known about how the prescription of opioids in Sweden has developed during the last decade. Aggregated data from the open Statistical database of the Swedish Board of Health and Welfare were analyzed descriptively. The yearly prevalence of opioid prescription did not change 2006-2015, but there were dramatic shifts in the choice of opioids. During this period, dextropropoxyphene was pulled off the market. Tramadol was used by fewer individuals (-54 % over the decade), but dosages expressed as Defined Daily Dose/patient/year (DDD/pat/y) increased (+41 %). In contrast, oxycodone and morphine were used by more individuals (+465 % and +137 %, respectively), but DDD/pat/y decreased during the period (-56% and -54%). Studies on non-aggregated data from available registries are needed to further elucidate the circumstances and possible consequences of these shifts in opioid prescription patterns.

  • 20.
    Böhme, Rebecca
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Charite, Germany.
    Lorenz, Robert C.
    Charite, Germany; Max Planck Institute Human Dev, Germany.
    Gleich, Tobias
    Charite, Germany; NeuroCure Excellence Cluster, Germany.
    Romund, Lydia
    Charite, Germany.
    Pelz, Patricia
    Charite, Germany.
    Golde, Sabrina
    Charite, Germany.
    Flemming, Eva
    Charite, Germany.
    Wold, Andrew
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Deserno, Lorenz
    Charite, Germany; Max Planck Institute Human Cognit and Brain Science, Germany; Otto von Guericke University, Germany.
    Behr, Joachim
    Charite, Germany; Charite, Germany; Medical School Brandenburg, Germany.
    Raufelder, Diana
    Freie University, Germany.
    Heinz, Andreas
    Charite, Germany.
    Beck, Anne
    Charite, Germany.
    Reversal learning strategy in adolescence is associated with prefrontal cortex activation2017In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 45, no 1, p. 129-137Article in journal (Refereed)
    Abstract [en]

    Adolescence is a critical maturation period for human cognitive control and executive function. In this study, a large sample of adolescents (n=85) performed a reversal learning task during functional magnetic resonance imaging. We analyzed behavioral data using a reinforcement learning model to provide individually fitted parameters and imaging data with regard to reward prediction errors (PE). Following a model-based approach, we formed two groups depending on whether individuals tended to update expectations predominantly for the chosen stimulus or also for the unchosen one. These groups significantly differed in their problem behavior score obtained using the child behavior checklist (CBCL) and in a measure of their developmental stage. Imaging results showed that dorsolateral striatal areas covaried with PE. Participants who relied less on learning based on task structure showed less prefrontal activation compared with participants who relied more on task structure. An exploratory analysis revealed that PE-related activity was associated with pubertal development in prefrontal areas, insula and anterior cingulate. These findings support the hypothesis that the prefrontal cortex is implicated in mediating flexible goal-directed behavioral control.

  • 21.
    Carlhäll, Sara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Källén, Karin
    Institution of Clinical Sciences Lund, Center for Reproductive Epidemiology, Tornblad Institute, Lund University, Lund, Sweden.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Blomberg, Marie
    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.
    Maternal plasma leptin levels in relation to the duration of the active phase of labor2018In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 97, no 10, p. 1248-1256Article in journal (Refereed)
    Abstract [en]

    Abstract Introduction Obese women have increased leptin levels and longer duration of labor compared with normal-weight women. Leptin has an inhibitory effect on myometrial contractility in vitro. Our purpose was to examine whether maternal leptin levels in active labor were associated with the duration of the active phase of labor. Material and methods This prospective cohort study included 914 women. Maternal blood samples were collected in active labor. The plasma-leptin concentration was obtained using a direct sandwich-based ELISA. Bivariate and multiple linear regression analyses were used to study the association between leptin levels and the duration of labor. Results A 1 ng/mL increase in maternal plasma leptin was associated with a 0.015 hour increase in duration of labor (P < .007). This association was not statistically significant in the adjusted analyses nor when analyzing nulliparous and multiparous women separately. In women with spontaneous labor (n = 766) leptin levels were not associated with an increase in duration of labor in the adjusted analyses. Conclusions There was no significant association between leptin levels and duration of the active phase of labor. Leptin in vivo might display a similar dose-response effect on myometrial contractility as demonstrated in in vitro studies. Future studies need to explore the association between leptin levels and time in labor in obese women with high leptin levels to evaluate a possible dose-response effect.

  • 22.
    Case, Laura K.
    et al.
    NIH, MD 20892 USA.
    Laubacher, Claire M.
    NIH, MD 20892 USA.
    Richards, Emily A.
    NIH, MD 20892 USA.
    Spagnolo, P. A.
    NIAAA, MD USA.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Bushnell, M. Catherine
    NIH, MD 20892 USA.
    Inhibitory rTMS of secondary somatosensory cortex reduces intensity but not pleasantness of gentle touch2017In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 653, p. 84-91Article in journal (Refereed)
    Abstract [en]

    Research suggests that the discriminative and affective aspects of touch are processed differently in the brain. Primary somatosensory cortex is strongly implicated in touch discrimination, whereas insular and prefronal regions have been associated with pleasantness aspects of touch. However, the role of secondary somatosensory cortex (S2) is less clear. In the current study we used inhibitory repetitive transcranial magnetic stimulation (rTMS) to temporarily deactivate S2 and probe its role in touch perception. Nineteen healthy adults received two sessions of 1-Hz rTMS on separate days, one targeting right S2 and the other targeting the vertex (control). Before and after rTMS, subjects rated the intensity and pleasantness of slow and fast gentle brushing of the hand and performed a 2-point tactile discrimination task, followed by fMRI during additional brushing. rTMS to S2 (but not vertex) decreased intensity ratings of fast brushing, without altering touch pleasantness or spatial discrimination. MRI showed a reduced response to brushing in S2 (but not in S1 or insula) after S2 rTMS. Together, our results show that reducing touch evoked activity in S2 decreases perceived touch intensity, suggesting a causal role of S2 in touch intensity perception. Published by Elsevier Ireland Ltd.

  • 23.
    Chae, Younbyoung
    et al.
    Kyung Hee University, South Korea.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    The role of touch in acupuncture treatment2017In: Acupuncture in Medicine, ISSN 0964-5284, E-ISSN 1759-9873, Vol. 35, no 2, p. 148-152Article, review/survey (Refereed)
    Abstract [en]

    Acupuncture is a therapeutic treatment that is characterised by the insertion of a needle at a particular location on the body. Acupuncture stimulation includes sensory-discriminative and affective-social touch dimensions. In this review, we discuss the role of touch during acupuncture stimulation with an emphasis on the therapeutic, sensory-discriminative and affective-social aspects. In the discriminative dimension, de qi, which is associated with needling, includes a combination of various sensations, such as heaviness, numbness, soreness and distension. Achieving the appropriate de qi sensation appears to be fundamental to the therapeutic outcome following acupuncture treatment. In the affective dimension, the acupuncture procedure typically includes gentle manual touch stimulation, which induces feelings of calm and well-being, perhaps by activating C tactile fibres. Enhanced activity of C tactile afferents may induce a limbic touch response, resulting in emotional and hormonal reactions. Because acupuncture is a therapist intensive and complex intervention, it is necessary to understand the role of social touch between the practitioner and patient. Both sensory-discriminative and affective-social touch aspects play an important role in the therapeutic effect of acupuncture treatment in clinical practice.

  • 24.
    Chau, David T.
    et al.
    Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.
    Fogelman, Phoebe
    University of Tennessee, Knoxville, Tennessee, USA.
    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, Department of Psychiatry.
    Drevets, Wayne C.
    Laureate Institute for Brain Research, Tulsa, Oklahoma, USA; Janssen Research and Development, Janssen Pharmaceuticals of Johnson and Johnson, Titusville, New Jersey, USA.
    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. Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.
    Distinct Neural-Functional Effects of Treatments With Selective Serotonin Reuptake Inhibitors, Electroconvulsive Therapy, and Transcranial Magnetic Stimulation and Their Relations to Regional Brain Function in Major Depression: A Meta-analysis2017In: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, ISSN 2451-9030, Vol. 2, no 4, p. 318-326Article in journal (Refereed)
    Abstract [en]

    Functional neuroimaging studies have examined the neural substrates of treatments for major depressive disorder (MDD). Low sample size and methodological heterogeneity, however, undermine the generalizability of findings from individual studies. We conducted a meta-analysis to identify reliable neural changes resulting from different modes of treatment for MDD and compared them with each other and with reliable neural functional abnormalities observed in depressed versus control samples.

  • 25.
    Checa, Antonio
    et al.
    Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Malmqvist, Anna
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Flyckt, Lena
    Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
    Schwieler, Lilly
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Samuelsson, Martin
    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 Psychiatry.
    Skogh, Elisabeth
    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 Psychiatry.
    Cervenka, Simon
    Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
    Dahl, Marja-Liisa
    Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Piehl, Fredrik
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Erhardt, Sophie
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Wheelock, Craig E.
    Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Cerebrospinal fluid levels of sphingolipids associate with disease severity in first episode psychosis patients2018In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 199, p. 438-441Article in journal (Other academic)
    Abstract [en]

    n/a

  • 26.
    Chermá, Maria D.
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Rydberg, Irene
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Woxler, Per
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Dependency in Linköping.
    Trygg, Tomas
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Dependency in Linköping.
    Hollertz, Olle
    Department of General Psychiatry, Västervik Hospital, Västervik, Sweden.
    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.
    Methylphenidate for Treating ADHD: A Naturalistic Clinical Study of Methylphenidate Blood Concentrations in Children and Adults With Optimized Dosage.2017In: European journal of drug metabolism and pharmacokinetics, ISSN 0378-7966, E-ISSN 2107-0180, Vol. 42, no 2, p. 295-307Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Methylphenidate (MPH), along with behavioral and psychosocial interventions, is the first-line medication to treat attention-deficit hyperactivity disorder (ADHD) in Sweden. The dose of MPH for good symptom control differs between patients. However, studies of MPH concentration measurement in ADHD treatment are limited.

    OBJECTIVE: To describe blood and oral fluid (OF) concentrations of MPH after administration of medication in patients with well-adjusted MPH treatment for ADHD, and to identify the most suitable matrix for accurate MPH concentration during treatment.

    METHODS: Patients were recruited from Child and Adolescent Psychiatry (CAP), General Psychiatry (GP), and the Department of Dependency (DD). Blood and OF samples were collected in the morning before MPH administration as well as 1 and 6 h after administration of the prescribed morning dose of MPH.

    RESULTS: Fifty-nine patients aged between 9 and 69 years, 76 % males. The daily dose of MPH varied from 18 to 180 mg, but the median daily dose per body weight was similar, approximately 1.0 mg/kg body weight. The median MPH concentration in blood 1 and 6 h after the morning dose was 5.4 and 9.3 ng/mL, respectively. Highly variable OF-to-blood ratios for MPH were found at all time points for all three groups.

    CONCLUSIONS: Weight is a reliable clinical parameter for optimal dose titration. Otherwise, MPH blood concentration might be used for individual dose optimization and for monitoring of the prescribed dose. Relying only on the outcome in OF cannot be recommended for evaluation of accurate MPH concentrations for treatment monitoring.

  • 27.
    Cortes, Carlos R.
    et al.
    NIAAA, MD 20892 USA.
    Grodin, Erica N.
    NIAAA, MD 20892 USA.
    Mann, Claire L.
    NIAAA, MD 20892 USA.
    Mathur, Karan
    NIAAA, MD 20892 USA.
    Kerich, Michael
    NIAAA, MD 20892 USA.
    Zhu, Xi
    NIAAA, MD 20892 USA.
    Schwandt, Melanie
    NIAAA, MD 20892 USA.
    Diazgranados, Nancy
    NIAAA, MD 20892 USA.
    George, David T.
    NIAAA, MD 20892 USA.
    Momenan, Reza
    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, Department of Psychiatry.
    Insula Sensitivity to Unfairness in Alcohol Use Disorder2018In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 53, no 3, p. 201-208Article in journal (Refereed)
    Abstract [en]

    Aims: Social decision making has recently been evaluated in alcohol use disorder (AUD) using the ultimatum game (UG) task, suggesting a possible deficit in aversive emotion regulation elicited by the unfairness during this task. Despite the relevance to relapse of this possible faulty regulation, the brain correlates of the UG in AUD are unknown. Methods: In total, 23 AUD and 27 healthy controls (HC) played three consecutive fMRI runs of the UG, while behavioral and brain responses were recorded. Results: Overall, acceptance rate of unfair offers did not differ between groups, but there was a difference in the rate of behavioral change across runs. We found significant anterior insula (aINS) activation in both groups for both fair and unfair conditions, but only HC showed a trend towards increased activation during unfair vs. fair offers. There were not overall whole-brain between-group significant differences. We found a trend of signal attenuation, instead of an increase, in the aINS for AUD when compared to HC during the third run, which is consistent with our recent findings of selective insula atrophy in AUD. Conclusion: We found differential group temporal dynamics of behavioral response in the UG. The HC group had a low acceptance rate for unfair offers in the first two runs that increased markedly for the third run; whereas the AUD group was consistent in their rejection of unfair offers across the three runs. We found a strong significant decrease in neural response across runs for both groups. Short summary: This fMRI study of UG in alcohol use disorder found behavioral group differences in acceptance rate across runs, which together with significant BOLD-signal decrease across runs in UG-related regions in both groups, highlights the impairment of strategy in AUD and the effect of repetitive exposure to unfairness in this task.

  • 28.
    Davidovic, Monika
    et al.
    Univ Gothenburg, Sweden.
    Karjalainen, Louise
    Univ Gothenburg, Sweden.
    Starck, Göran
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Wentz, Elisabet
    Univ Gothenburg, Sweden.
    Björnsdotter Åberg, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Gothenburg, Sweden.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Gothenburg, Sweden.
    Abnormal brain processing of gentle touch in anorexia nervosa2018In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 281, p. 53-60Article in journal (Refereed)
    Abstract [en]

    Body image disturbance is a core symptom in anorexia nervosa (AN). Recent research suggests that abnormalities in touch perception may contribute to the disease mechanisms in AN. Here, we used functional magnetic resonance imaging (fMRI) to study possible abnormalities in cortical processing of affective touch in AN. Gentle skin strokes were applied to the right forearm during fMRI scanning in women diagnosed with AN (n = 25) and in matched healthy controls (HC; n = 25). Blocks of skin stroking were alternated with blocks of static skin indentation. Participants provided ratings of the pleasantness of skin stroking stimulation. AN participants perceived skin stroking as significantly less pleasant than HC. We observed no group differences for the contrast between skin stroking and skin indentation in primary tactile regions. We did find, however, significantly less activity in the AN group in areas including left caudate nucleus. Also, we found less activity in the AN group in bilateral lateral occipital cortex for the main effect of skin stroking. Our results suggest that abnormal functioning of the dorsal striatum could affect evaluation of pleasant tactile stimuli, and that abnormal functioning of the lateral occipital cortex might be related to disturbed body image perception.

  • 29.
    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.
    Barbier, Estelle
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Eric
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Gaëlle
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Gehlert, D.
    Cerecor, MD USA; Matrix Pharmaceut Consulting, CO USA.
    Barchiesi, Riccardo
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Holm, Lovisa
    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, Department of Psychiatry.
    Preclinical evaluation of the kappa-opioid receptor antagonist CERC-501 as a candidate therapeutic for alcohol use disorders2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 9, p. 1805-1812Article in journal (Refereed)
    Abstract [en]

    Prior work suggests a role of kappa-opioid signaling in the control of alcohol drinking, in particular when drinking is escalated due to alcohol-induced long-term neuroadaptations. Here, we examined the small molecule selective kappa antagonist CERC-501 in rat models of alcohol-related behaviors, with the objective to evaluate its potential as a candidate therapeutic for alcohol use disorders. We first tested the effect of CERC-501 on acute alcohol withdrawal-induced anxiety-like behavior. CERC-501 was then tested on basal as well as escalated alcohol self-administration induced by 20% alcohol intermittent access. Finally, we determined the effects of CERC-501 on relapse to alcohol seeking triggered by both stress and alcohol-associated cues. Control experiments were performed to confirm the specificity of CERC-501 effects on alcohol-related behaviors. CERC-501 reversed anxiety-like behavior induced by alcohol withdrawal. It did not affect basal alcohol self-administration but did dose-dependently suppress self-administration that had escalated following long-term intermittent access to alcohol. CERC-501 blocked relapse to alcohol seeking induced by stress, but not when relapse-like behavior was triggered by alcohol-associated cues. The effects of CERC-501 were observed in the absence of sedative side effects and were not due to effects on alcohol metabolism. Thus, in a broad battery of preclinical alcohol models, CERC-501 has an activity profile characteristic of anti-stress compounds. Combined with its demonstrated preclinical and clinical safety profile, these data support clinical development of CERC-501 for alcohol use disorders, in particular for patients with negatively reinforced, stress-driven alcohol seeking and use.

  • 30.
    Dunn, James S.
    et al.
    University of Western Sydney, Australia.
    Mahns, David A.
    University of Western Sydney, Australia.
    Nagi, Saad S.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. University of Western Sydney, Australia.
    Why does a cooled object feel heavier? Psychophysical investigations into the Webers Phenomenon2017In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 18, article id 4Article in journal (Refereed)
    Abstract [en]

    Background: It has long been known that a concomitantly cooled stimulus is perceived as heavier than the same object at a neutral temperature-termed Webers Phenomenon (WP). In the current study, we re-examined this phenomenon using well-controlled force and temperature stimuli to explore the complex interplay between thermal and tactile systems, and the peripheral substrates contributing to these interactions. A feedback-controlled apparatus was constructed using a mechanical stimulator attached to a 5- x 5-mm thermode. Force combinations of 0.5 and 1 N (superimposed on 1-N step) were applied to the ulnar territory of dorsal hand. One of the forces had a thermal component, being cooled from 32 to 28 degrees C at a rate of 2 degrees C/s with a 3-s static phase. The other stimulus was thermally neutral (32 degrees C). Participants were asked to report whether the first or the second stimulus was perceived heavier. These observations were obtained in the all-fibre-intact condition and following the preferential block of myelinated fibres by compression of ulnar nerve. Results: In normal condition, when the same forces were applied, all subjects displayed a clear preference for the cooled tactile stimulus as being heavier than the tactile-only stimulus. The frequency of this effect was augmented by an additional similar to 17% when cooling was applied concurrently with the second stimulus. Following compression block, the mean incidence of WP was significantly reduced regardless of whether cooling was applied concurrently with the first or the second stimulus. However, while the effect was abolished in case of former (elicited in amp;lt; 50% of trials), the compression block had little effect in four out of nine participants in case of latter who reported WP in at least 80% of trials (despite abolition of vibration and cold sensations). Conclusions: WP was found to be a robust tactile-thermal interaction in the all-fibre-intact condition. The emergence of inter-individual differences during myelinated block suggests that subjects may adopt strategies, unbeknownst to them, that focus on the dominant input (myelinated fibres, hence WP abolished by block) or the sum of convergent inputs (myelinated and C fibres, hence WP preserved during block) in order to determine differences in perceived heaviness.

  • 31.
    Emilsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Department of Health Science, University West, Trollhättan, Sweden.
    Treatment adherence in Asthma and Attention Deficit Hyperactivity Disorder (ADHD), Personality traits, Beliefs about medication and Illness perception2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Adherence to medication in asthma and attention deficit hyperactivity disorder (ADHD) is important because medication may prevent serious consequences, possibly with lifelong effects. Several factors have been identified that influence adherence to medication in these disorders, but the importance of personality traits, beliefs about medication and illness perception has been insufficiently explored.

    The overall aim of this thesis was to study adherence to medication in asthma and ADHD, and in particular factors associated with adherence.

    The participants (n=268) in Study I were recruited epidemiologically and consisted of young adults with asthma, aged 22 years (±1 year). Impulsivity and, in men Antagonism and Alexithymia were associated with low adherence among respondents with regular asthma medication (n=109).

    The participants (n=35) in Study II were recruited from primary care clinics and consisted of adults (mean age 53 years). In men, Neuroticism was associated with low adherence, but Conscientiousness with high adherence. Beliefs about the necessity of medication were positively associated with adherence behaviour in women. In the total sample, a positive necessity-concern differential of beliefs predicted higher adherence.

    The participants in Study III, IV (n=101) and V (n=99) were recruited from Child and Adolescent Psychiatric clinics and consisted of adolescents with ADHD on long-term ADHD medication. Study IV assessed the reliability and validity of Swedish translations of the Beliefs about Medicines Questionnaire-specific (BMQ-Specific) and Brief Illness Perception Questionnaire (B-IPQ) for use in adolescents with ADHD. Exploratory Principal Component Analysis (PCA) loadings of the BMQ-Specific items confirmed the original components, the specific-necessity and specific-concerns. The exploratory PCA for B-IPQ revealed two components; the first one, B-IPQ Consequences, captured questions regarding perceptions of the implication of having ADHD (items 1, 2, 5, 6 and 8) and the second one, B-IPQ-Control, the perceptions of the ability to manage the ADHD disorder (items 3, 4 and 7). Adherence correlated positively with BMQ-necessity-concern differential but negatively with beliefs about medication regarding concerns and side effects as well as Antagonism. Adolescents with more beliefs in the necessity, but with less concerns and side effects were less intentionally non-adherent. Adolescents with more perceptions that ADHD affected life showed less unintentional non-adherence. Negative Affectivity was associated with beliefs in the necessity of medication, but also with concern about medication and side effects. Negative Affectivity was positively associated with perceived consequences in life caused by ADHD and less control over ADHD. Hedonic Capacity was associated with less concerns about medication.

    In conclusion: In asthma and ADHD, adherence was associated with personality and beliefs about medications treatment. The personality traits showed numerous associations with perception about ADHD and beliefs about asthma and ADHD medication. This thesis increases our understanding of these person-related underlying factors of non-adherence, which may enable targeted actions intended to turn non-adherence into adherence as well as to identify individuals at risk for non-adherence. The Swedish translation of BMQ-Specific and B-IPQ proved to be valid and reliable, suggesting that the scales are useful in clinical work to identify risks of low adherence and to increase knowledge about how adolescents perceive ADHD. 

    List of papers
    1. Personality, adherence, asthma control and health-related quality of life in young adult asthmatics
    Open this publication in new window or tab >>Personality, adherence, asthma control and health-related quality of life in young adult asthmatics
    Show others...
    2009 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 103, no 7, p. 1033-1040Article in journal (Refereed) Published
    Abstract [en]

    Background

    Striving for improved adherence and asthma control is of vital concern in today's asthma management. Several influential factors have been identified, but the importance of personality traits has been insufficiently explored. The aim was first to determine whether personality traits in young adult asthmatics are related to asthma control and health-related quality of life (HRQL), and second to examine the influences of personality traits on adherence to regular asthma medication treatment.

    Methods

    Young adult asthmatics, 22 years of age (n = 268) completed questionnaires. Statistical analyses were performed.

    Results

    The personality traits Negative Affectivity and Impulsivity correlated negatively with asthma control, whereas in women Hedonic Capacity correlated positively with asthma control. Negative Affectivity, Impulsivity, Hedonic Capacity, Alexithymia and asthma control predicted the mental dimension of HRQL. Asthma control and physical activity predicted the physical dimension of HRQL. Among respondents with regular asthma medication (n = 109), Impulsivity correlated negatively with adherence. In men, Antagonism and Alexithymia were associated with low adherence. Additionally, Alexithymia, Hedonic Capacity and Negative Affectivity showed non-linear relationships with adherence, meaning that initially increased scores on these personality traits scales were associated with increased adherence but higher scores did not increase adherence. Respondents who were prescribed a single inhaler combining ICS and LABA reported higher adherence than those with monotherapies.

    Conclusion

    These data suggest that personality can influence how asthma patients adhere to asthma medication treatment, and report their control and HRQL. Tools determining personality traits may be useful in the future in individualizing management of asthma patients.

    Place, publisher, year, edition, pages
    Elsevier, 2009
    Keywords
    Adherence, Asthma, Asthma control, Health-related quality of life, Personality traits, Young adults
    National Category
    Nursing
    Research subject
    NURSING AND PUBLIC HEALTH SCIENCE, Nursing science
    Identifiers
    urn:nbn:se:liu:diva-142758 (URN)10.1016/j.rmed.2009.01.013 (DOI)09546111 (ISSN) (ISBN)
    Available from: 2009-09-21 Created: 2017-11-02 Last updated: 2017-11-02Bibliographically approved
    2. The Influence of personality traits and beliefs about medicines on adherence to asthma treatment
    Open this publication in new window or tab >>The Influence of personality traits and beliefs about medicines on adherence to asthma treatment
    Show others...
    2011 (English)In: Primary Care Respiratory Journal, ISSN 1471-4418, E-ISSN 1475-1534, Vol. 20, no 2, p. 141-147Article, review/survey (Refereed) Published
    Abstract [en]

    Aim:To explore the influence of personality traits and beliefs about medicines on adherence to treatment with asthma medication.

    Methods:Respondents were 35 asthmatic adults prescribed controller medication. They answered questionnaires about medication adherence, personality traits, and beliefs about medicines.

    Results:In gender comparisons, the personality traits “Neuroticism” in men and “adherence to medication” were associated with lower adherent behaviour. Associations between personality traits and beliefs in the necessity of medication for controlling the illness were identified. Beliefs about the necessity of medication were positively associated with adherent behaviour in women. In the total sample, a positive “necessity-concern” differential predicted adherent behaviour.

    Conclusion:The results imply that personality and beliefs about medicines may influence how well adults with asthma adhere to treatment with asthma medication.

    Place, publisher, year, edition, pages
    The Primary Care Respiratory Society U K, 2011
    Keywords
    adherence, asthma, medication beliefs, personality traits, treatment
    National Category
    Nursing
    Research subject
    NURSING AND PUBLIC HEALTH SCIENCE, Nursing science
    Identifiers
    urn:nbn:se:liu:diva-142759 (URN)10.4104/pcrj.2011.00005 (DOI)
    Available from: 2011-02-18 Created: 2017-11-02 Last updated: 2017-11-29Bibliographically approved
    3. Beliefs regarding medication and side effects influence treatment adherence in adolescents with attention deficit hyperactivity disorder
    Open this publication in new window or tab >>Beliefs regarding medication and side effects influence treatment adherence in adolescents with attention deficit hyperactivity disorder
    2017 (English)In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 26, no 5, p. 559-571Article in journal (Refereed) Published
    Abstract [en]

    Adherence to attention deficit hyperactivity disorder (ADHD) treatment is important because, when untreated, it may have serious consequences with lifelong effects. In the case of adolescents on long-term medicine prescription, more knowledge is needed regarding adherence and factors influencing adherence, which was the purpose of this study. Adolescents (n = 101) on ADHD medication ≥6 months were administrated questionnaires at a monitoring appointment: Medication Adherence Report Scale (MARS), beliefs about medicines (BMQ) and the Brief Illness Perception Questionnaire (B-IPQ). Adherence was high, the mean value was 88% of the maximum MARS score, and correlated positively with the “BMQ-necessity-concerns differential” but negatively with “BMQ-concerns” and “BMQ-side effects”. Adolescents with more belief in the necessity of the medication, less concerns and less experience of side effects tended to be more adherent to medication prescription (“intentional non-adherence”), while “unintentional non-adherence” (forgetfulness) was associated with how much they perceived that their ADHD affected their lives. In a multiple regression model, the variance of MARS total (R2 = 0.21) and “intentional non-adherence” (R2 = 0.24) was explained by the “BMQ-necessity–concern differential” and “BMQ-experienced side effects”. The variance of “unintentional non-adherence” (R2 = 0.12) was explained by the “BMQ-necessity–concern differential” and “B-IPQ-consequences of ADHD”. In conclusion, adolescents on long-term medication reported good adherence, mainly influenced by more beliefs in the necessity versus concerns of the medications, less experienced side effects and more perceived consequences of ADHD. BMQ could be useful to identify risks of low adherence, which should be counteracted by partially gender-specific interventions.

    Place, publisher, year, edition, pages
    Springer, 2017
    Keywords
    Electron beam melting, IN718, microstructure, texture, hardness
    National Category
    Psychiatry
    Identifiers
    urn:nbn:se:liu:diva-132825 (URN)10.1007/s00787-016-0919-1 (DOI)000399701900007 ()27848023 (PubMedID)
    Note

    Funding agencies: Medical Research Council of Southeast Sweden [FORSS-466211]; "Child and Youth Studies" at the University West

    Available from: 2016-11-30 Created: 2016-11-30 Last updated: 2018-04-18Bibliographically approved
  • 32.
    Emilsson, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Department of Health Science, Section of Nursing Graduate Level, University West, Trollhättan, Sweden.
    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.
    Öhnström, Gisela
    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.
    Marteinsdottir, Ina
    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 Psychiatry.
    Beliefs regarding medication and side effects influence treatment adherence in adolescents with attention deficit hyperactivity disorder2017In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 26, no 5, p. 559-571Article in journal (Refereed)
    Abstract [en]

    Adherence to attention deficit hyperactivity disorder (ADHD) treatment is important because, when untreated, it may have serious consequences with lifelong effects. In the case of adolescents on long-term medicine prescription, more knowledge is needed regarding adherence and factors influencing adherence, which was the purpose of this study. Adolescents (n = 101) on ADHD medication ≥6 months were administrated questionnaires at a monitoring appointment: Medication Adherence Report Scale (MARS), beliefs about medicines (BMQ) and the Brief Illness Perception Questionnaire (B-IPQ). Adherence was high, the mean value was 88% of the maximum MARS score, and correlated positively with the “BMQ-necessity-concerns differential” but negatively with “BMQ-concerns” and “BMQ-side effects”. Adolescents with more belief in the necessity of the medication, less concerns and less experience of side effects tended to be more adherent to medication prescription (“intentional non-adherence”), while “unintentional non-adherence” (forgetfulness) was associated with how much they perceived that their ADHD affected their lives. In a multiple regression model, the variance of MARS total (R2 = 0.21) and “intentional non-adherence” (R2 = 0.24) was explained by the “BMQ-necessity–concern differential” and “BMQ-experienced side effects”. The variance of “unintentional non-adherence” (R2 = 0.12) was explained by the “BMQ-necessity–concern differential” and “B-IPQ-consequences of ADHD”. In conclusion, adolescents on long-term medication reported good adherence, mainly influenced by more beliefs in the necessity versus concerns of the medications, less experienced side effects and more perceived consequences of ADHD. BMQ could be useful to identify risks of low adherence, which should be counteracted by partially gender-specific interventions.

  • 33.
    Epstein, David H.
    et al.
    NIDA, MD 21224 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, Department of Psychiatry.
    Shaham, Yavin
    NIDA, MD 21224 USA.
    Science-Based Actions Can Help Address the Opioid Crisis2018In: TIPS - Trends in Pharmacological Sciences, ISSN 0165-6147, E-ISSN 1873-3735, Vol. 39, no 11, p. 911-916Article in journal (Other academic)
    Abstract [en]

    The epidemic of addiction and over-dose is real. Addiction among pain patients accounts for only a small proportion but a large number. Scientific opinion leaders can be most effective on two fronts, each relatively low-tech: dissemination and oversight of empirically established treatments, and promulgation of social-science-based strategies for population-level prevention.

  • 34.
    Eskilsson, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Matsuwaki, Takashi
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Shionoya, Kiseko
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Mirrasekhian, Elahe
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Zajdel, Joanna
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Schwaninger, Markus
    University of Lubeck, Germany.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Blomqvist, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Immune-Induced Fever Is Dependent on Local But Not Generalized Prostaglandin E-2 Synthesis in the Brain2017In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 37, no 19, p. 5035-5044Article in journal (Refereed)
    Abstract [en]

    Fever occurs upon binding of prostaglandin E-2 (PGE(2)) to EP3 receptors in the median preoptic nucleus of the hypothalamus, but the origin of the pyrogenic PGE(2) has not been clearly determined. Here, using mice of both sexes, we examined the role of local versus generalized PGE(2) production in the brain for the febrile response. In wild-type mice and in mice with genetic deletion of the prostaglandin synthesizing enzyme cyclooxygenase-2 in the brain endothelium, generated with an inducible CreER(T2) under the Slco1c1 promoter, PGE(2) levels in the CSF were only weakly related to the magnitude of the febrile response, whereas the PGE(2) synthesizing capacity in the hypothalamus, as reflected in the levels of cyclooxygenase-2 mRNA, showed strong correlation with the immune-induced fever. Histological analysis showed that the deletion of cyclooxygenase-2 in brain endothelial cells occurred preferentially in small-and medium-sized vessels deep in the brain parenchyma, such as in the hypothalamus, whereas larger vessels, and particularly those close to the neocortical surface and in the meninges, were left unaffected, hence leaving PGE(2) synthesis largely intact in major parts of the brain while significantly reducing it in the region critical for the febrile response. Furthermore, injection of a virus vector expressing microsomal prostaglandin E synthase-1 (mPGES-1) into the median preoptic nucleus of fever-refractive mPGES-1 knock-out mice, resulted in a temperature elevation in response to LPS. We conclude that the febrile response is dependent on local release of PGE(2) onto its target neurons and not on the overall PGE(2) production in the brain.

  • 35.
    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.
    Dahlström, Örjan
    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.
    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.
    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.
    Pribe, Gisela
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden.
    Adolescents motives for selling sex in a welfare state - A Swedish national study2018In: International Journal of Child Abuse & Neglect, ISSN 0145-2134, E-ISSN 1873-7757, Vol. 81, p. 286-295Article in journal (Refereed)
    Abstract [en]

    In addition to money or other compensation, other motives for selling sex may be important in a welfare country such as Sweden. The aim of this study was to carry out an exploratory investigation of adolescents motives for selling sex in a population-based survey in Sweden. A total of 5839 adolescents from the third year of Swedish high school, mean age 18.0 years, participated in the study. The response rate was 59.7% and 51 students (0.9%) reported having sold sex. Exploratory factor analysis and hierarchical cluster analysis were used to identify groups of adolescents according to underlying motives for selling sex. Further analyses were carried out for characteristics of selling sex and risk factors. Three groups of adolescents were categorized according to their motives for selling sex: Adolescents reporting; 1) Emotional reasons, being at a greater risk of sexual abuse, using sex as a means of self-injury and having a non-heterosexual orientation. 2) Material but no Emotional reasons, who more often receive money as compensation and selling sex to a person over 25 years of age, and 3) Pleasure or no underlying motive for selling sex reported, who were mostly heterosexual males selling sex to a person under 25 years of age, the buyer was not known from the Internet, the reward was seldom money and this group was less exposed to penetrative sexual abuse or using sex as a means of self-injury. In conclusion, adolescents selling sex are a heterogeneous group in regard to underlying motives.

    The full text will be freely available from 2021-05-05 00:01
  • 36.
    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, Department of Child and Adolescent Psychiatry in Linköping.
    Svedin, Carl Göran
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Pribe, Gisela
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. 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.
    Wadsby, Marie
    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.
    Self-reported frequency of sex as self-injury (SASI) in a national study of Swedish adolescents and association to sociodemographic factors, sexual behaviors, abuse and mental health2017In: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 11, no 1Article in journal (Refereed)
    Abstract [en]

    Sex as self-injury has become a concept in Swedish society; however it is a largely unexplored area of research, not yet conceptualized and far from accepted in the research field. The use of sex as a way of affect regulation is known in the literature and has, in interviews with young women who sell sex, been compared to direct self-injury, such as cutting or burning the skin. The aim of this study was to investigate the self-reported frequency of sex as self-injury and the association to sociodemographic factors, sexual orientation, voluntary sexual experiences, sexual risk-taking behaviors, sexual, physical and mental abuse, trauma symptoms, healthcare for psychiatric disorders and non-suicidal self-injury.

  • 37.
    Fritz, Michael
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Klawonn, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Jaarola, Maarit
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience.
    Interferon-ɣ mediated signaling in the brain endothelium is critical for inflammation-induced aversion2018In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 67, p. 54-58Article in journal (Refereed)
    Abstract [en]

    Systemic inflammation elicits malaise and a negative affective state. The mechanism underpinning the aversive component of inflammation include cerebral prostaglandin synthesis and modulation of dopaminergic reward circuits, but the messengers that mediate the signaling between the peripheral inflammation and the brain have not been sufficiently characterized. Here we investigated the role of interferon-ɣ (IFN-ɣ) in the aversive response to systemic inflammation induced by a low dose (10μg/kg) of lipopolysaccharide (LPS) in mice. LPS induced IFN-ɣ expression in the blood and deletion of IFN-ɣ or its receptor prevented the development of conditioned place aversion to LPS. LPS induced expression of the chemokine Cxcl10 in the striatum of normal mice, but this induction was absent in mice lacking IFN-ɣ receptors or Myd88 in blood brain barrier endothelial cells. Furthermore, inflammation-induced aversion was blocked in mice lacking Cxcl10 or its receptor Cxcr3. Finally, mice with a selective deletion of the IFN-ɣ receptor in brain endothelial cells did not develop inflammation-induced aversion, demonstrating that the brain endothelium is the critical site of IFN-ɣ action. Collectively, these findings show that circulating IFN-ɣ that binds to receptors on brain endothelial cells and induces Cxcl10, is a central link in the signaling chain eliciting inflammation-induced aversion.

  • 38.
    Gandhi, Wiebke
    et al.
    McGill University, Canada; University of Reading, England.
    Morrison, India
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Schweinhardt, Petra
    McGill University, Canada; McGill University, Canada; Balgrist University Hospital, Switzerland.
    How Accurate Appraisal of Behavioral Costs and Benefits Guides Adaptive Pain Coping2017In: Frontiers in Psychiatry, ISSN 1664-0640, E-ISSN 1664-0640, Vol. 8, article id 103Article, review/survey (Refereed)
    Abstract [en]

    Coping with pain is a complex phenomenon encompassing a variety of behavioral responses and a large network of underlying neural circuits. Whether pain coping is adaptive or maladaptive depends on the type of pain (e.g., escapable or inescapable), personal factors (e.g., individual experiences with coping strategies in the past), and situational circumstances. Keeping these factors in mind, costs and benefits of different strategies have to be appraised and will guide behavioral decisions in the face of pain. In this review we present pain coping as an unconscious decision-making process during which accurately evaluated costs and benefits lead to adaptive pain coping behavior. We emphasize the importance of passive coping as an adaptive strategy when dealing with ongoing pain and thus go beyond the common view of passivity as a default state of helplessness. In combination with passive pain coping, we highlight the role of the reward system in reestablishing affective homeostasis and discuss existing evidence on a behavioral and neural level. We further present neural circuits involved in the decision-making process of pain coping when circumstances are ambiguous and, therefore, costs and benefits are difficult to anticipate. Finally, we address the wider implications of this topic by discussing its relevance for chronic pain patients.

  • 39.
    Gustafsson, Berit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Högland Hospital, Sweden; Jonköping University, Sweden; Hogland Hospital, Sweden.
    Proczkowska-Björklund, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Hospital Jonköping, Sweden.
    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.
    Emotional and behavioural problems in Swedish preschool children rated by preschool teachers with the Strengths and Difficulties Questionnaire (SDQ)2017In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 17, no 110Article in journal (Refereed)
    Abstract [en]

    Background: There is a high risk that young children who show early signs of mental health problems develop symptoms in the same or overlapping areas some years later. The Strengths and Difficulties Questionnaire (SDQ) is widely used to screen externalizing and internalizing problems early in life. In Sweden 80-90% of all children aged 1-5 years go to preschool and preschool is thus an appropriate context for finding early signs of mental health problems among children. Methods: This study is part of a longitudinal project too investigate the frequency of emotional and behavioural problems for children between 1 and 5 years of age in Sweden. The SDQ including the impairment supplement questions were rated by preschool teachers too establish Swedish norms for SDQ in preschool children. Results: The sample involved 815 children with a mean age of 42 months (SD = 16, range 13-71 months). 195 children were followed longitudinally for three years. There were significant differences between boys and girls on all subscales except for the Emotional subscale. The prevalence of behavioural problems was similar to other that in European countries, except for Prosocial behaviour, which was rated lower, and Conduct problems, rated higher. Swedish children were estimated to have more problems in the preschool setting, scored by preschool teachers. The development of behaviour over time differed for the different subscales of SDQ. Conclusions: The teacher version of the SDQ, for 2-4 year-olds, can be used as a screening instrument to identify early signs of emotional distress/behavioural problems in young children. Preschool teachers seem to be able to identify children with problematic behaviour with the use of SDQ at an early age. The development of behaviour over time differs for the different subscales of SDQ. The Swedish norms for SDQ are to a large extent, similar to findings from other European countries.

  • 40.
    Habig, Kathrin
    et al.
    Justus Liebig University, Germany.
    Schaenzer, Anne
    Justus Liebig University, Germany.
    Schirner, Wolfgang
    Justus Liebig University, Germany.
    Lautenschlaeger, Gothje
    Justus Liebig University, Germany.
    Dassinger, Benjamin
    Justus Liebig University, Germany.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Birklein, Frank
    Johannes Gutenberg University of Mainz, Germany.
    Gizewski, Elke R.
    Medical University of Innsbruck, Austria.
    Kraemer, Heidrun H.
    Justus Liebig University, Germany.
    Low threshold unmyelinated mechanoafferents can modulate pain2017In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 17, article id 184Article in journal (Refereed)
    Abstract [en]

    Background: Human, hairy skin contains a subgroup of C-fibers, the C-low threshold mechanoreceptive afferents ((C-LTMR) C-tactile or C-touch (CT) fibers) that are linked with the signaling of affective aspects of human touch. Recent studies suggest an involvement of these afferents in the modulation of pain in healthy volunteers. Small fiber neuropathy (SFN) is associated with a damage of C-fibers. Therefore, an impairment of C-LTMRs can be assumed. We aimed to elaborate a possible role of CT-afferents in pain modulation by investigating healthy volunteers and SFN-patients. Methods: Experiment I: 20 SFN-patients (12 women, median age 52.0 years) and 20 healthy controls (14 women, median age 43.0 years) participated in this prospective fMRI and psychophysical study. Heat-pain (HP), CT-targeted touch (slow brushing) and HP combined with CT-targeted touch were applied in randomized order to the left shank in a block design. The participants rated pain intensity on a visual analogue scale. Experiment II: We investigated a possible impact of pain intensity on CT induced pain modulation (10 healthy participants). The intensity of HP stimulation was chosen to induce pain intensity 50/100 (NRS). HP stimulation was applied with and without CT-targeted touch. Results: Experiment I: CT-stimulation was sufficient to reduce heat pain in healthy participants (p = 0.016), but not in SFN-patients. HP induced pain intensity was significantly higher (32,2 vs 52,6) in SFN-patients. During HP, bold responses in pain associated areas were observed in both groups. Additional CT-stimulation elicited no significant difference of bold responses compared to HP. Experiment II: In healthy volunteers, we reproduced a significant reduction of HP intensity by CT-stimulation (p = 0.038). Conclusions: CT input seems to be sufficient to modulate pain, independent of intensity of the pain stimulus. As a prerequisite, the CT fibers have to be intact as in healthy volunteers. If CT fibers are impaired -as in SFN-, CT-targeted touch does not modulate pain intensity. The location of CT-induced pain modulation might be attributed to the level of the dorsal horn since the cortical activation pattern of heat pain with and without CT-targeted touch did not differ in healthy subjects and in SFN-patients.

  • 41.
    Hansson, Anita C.
    et al.
    Heidelberg Univ, Germany.
    Koopmann, Anne
    Heidelberg Univ, Germany.
    Uhrig, Stefanie
    Heidelberg Univ, Germany.
    Buhler, Sina
    Heidelberg Univ, Germany.
    Domi, Esi
    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.
    Kiessling, Eva
    Heidelberg Univ, Germany.
    Ciccocioppo, Roberto
    Univ Camerino, Italy.
    Froemke, Robert C.
    NYU, NY USA.
    Grinevich, Valery
    German Canc Res Ctr, Germany.
    Kiefer, Falk
    Heidelberg Univ, Germany.
    Sommer, Wolfgang H.
    Heidelberg Univ, Germany; Heidelberg Univ, Germany.
    Vollstaedt-Klein, Sabine
    Heidelberg Univ, Germany.
    Spanagel, Rainer
    Heidelberg Univ, Germany.
    Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 6, p. 1235-1246Article in journal (Refereed)
    Abstract [en]

    Approved pharmacological treatments for alcohol use disorder are limited in their effectiveness, and new drugs that can easily be translated into the clinic are warranted. One of those candidates is oxytocin because of its interaction with several alcohol-induced effects. Alcoholdependent rats as well as post-mortem brains of human alcoholics and controls were analyzed for the expression of the oxytocin system by qRT-PCR, in situ hybridizaton, receptor autoradiography ([(125)l]OVTA binding), and immunohistochemistry. Alcohol self administration and cue-induced reinstatement behavior was measured after intracerebroventicular injection of 10 nM oxytocin in dependent rats. Here we show a pronounced upregulation of oxytocin receptors in brain tissues of alcohol dependent rats and deceased alcoholics, primarily in frontal and striatal areas. This upregulation stems most likely from reduced oxytocin expression in hypothalamic nuclei. Pharmacological validaton showed that oxytocin reduced cue-induced reinstatement response in dependent rats-an effect that was not observed in nondependent rats. Finally, a clinical pilot study (German clinical trial number DRKS00009253) using functional magnetic resonance imaging in heavy social male drinkers showed that intranasal oxytocin (24 IU) decreased neural cue-reactivity in brain networks similar to those detected in dependent rats and humans with increased oxytocin receptor expression. These studies suggest that oxytocin might be used as an anticraving medication and thus may positvely affect treatment outcomes in alcoholics.

  • 42.
    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, Department of Psychiatry.
    Barbier, Estelle
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience.
    Johnstone, A. L.
    University of Miami, FL 33136 USA.
    Tapocik, J.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Meinhardt, M. W.
    Heidelberg University, Germany.
    Pfarr, S.
    Heidelberg University, Germany.
    Wahlestedt, C.
    University of Miami, FL 33136 USA.
    Sommer, W. H.
    Heidelberg University, Germany.
    Reprogramming of mPFC transcriptome and function in alcohol dependence2017In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 16, no 1, p. 86-100Article, review/survey (Refereed)
    Abstract [en]

    Despite its limited immediate reinforcement value, alcohol has a potent ability to induce neuroadaptations that promote its incentive salience, escalation of voluntary alcohol intake and aversion-resistant alcohol seeking. A constellation of these traits, collectively called post-dependent, emerges following brain exposure to repeated cycles of intoxication and withdrawal. The medial prefrontal cortex (mPFC) and its subdivisions exert top-down regulation of approach and avoidance behaviors, including those that lead to alcohol intake. Here, we review an emerging literature which indicates that a reprogramming of mPFC function occurs with prolonged exposure of the brain to cycles of alcohol intoxication and withdrawal. This reprogramming results in molecular dysregulations that contribute to the post-dependent syndrome. Convergent evidence has identified neuroadaptations resulting in altered glutamatergic and BDNF-mediated signaling, and for these pathways, direct evidence for a mechanistic role has been obtained. Additional evidence points to a dysregulation of pathways involving calcium homeostasis and neurotransmitter release. Recent findings indicate that global DNA hypermethylation is a key factor in reprogramming the mPFC genome after a history of dependence. As one of the results of this epigenetic remodeling, several histone modifying epigenetic enzymes are repressed. Among these, PR-domain zinc-finger protein 2, a methyltransferase that selectively mono-methylates histone H3 at lysine 9 has been functionally validated to drive several of the molecular and behavioral long-term consequences of alcohol dependence. Information processing within the mPFC involves formation of dynamic neuronal networks, or functional ensembles that are shaped by transcriptional responses. The epigenetic dysregulations identified by our molecular studies are likely to alter this dynamic processing in multiple ways. In summary, epigenetic molecular switches in the mPFC appear to be turned on as alcoholism develops. Strategies to reverse these processes may offer targets for disease-modifying treatments.

  • 43.
    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, Department of Psychiatry.
    Tagil, Magnus
    Department of Orthopedics, Clinical Sciences, Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Editorial Material: Do we have an opioid crisis in Scandinavia? Time to act? in ACTA ORTHOPAEDICA, vol 89, issue 4, pp 368-3682018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 4, p. 368-368Article in journal (Other academic)
    Abstract [en]

    n/a

  • 44.
    Holm, Jonas
    et al.
    Örebro University, Sweden.
    Brus, Ole
    Örebro University, Sweden.
    Bave, Ullvi
    Karolinska Institute, Sweden.
    Landen, Mikael
    Karolinska Institute, Sweden; Gothenburg University, Sweden.
    Lundberg, Johan
    Karolinska Institute, 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, Department of Psychiatry.
    von Knorring, Lars
    Uppsala University, Sweden.
    Nordenskjold, Axel
    Örebro University, Sweden.
    Improvement of cycloid psychosis following electroconvulsive therapy2017In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 71, no 6, p. 405-410Article in journal (Refereed)
    Abstract [en]

    Background: The treatment of choice for cycloid psychosis has traditionally been electroconvulsive therapy (ECT), but there is a lack of studies on its effectiveness.Aims: The primary aim of this register study was to determine the rates of remission and response after ECT for cycloid psychosis. The secondary aim was to examine possible predictors of outcome.Methods: Data were obtained from the National Quality Register for ECT in Sweden. The study population was patients (n=42) who received ECT for acute polymorphic psychotic disorder without symptoms of schizophrenia or for cycloid psychosis between 2011-2015 in 13 hospitals. Remission and response rates were calculated using Clinical Global Impression-Severity (CGI-S) and -Improvement scores, respectively. Variables with possible predictive value were tested using Chi-square and Fishers exact test.Results: The response rate was 90.5%. The remission rate was 45.2%. Of 42 patients, 40 improved their CGI-S score after ECT (pamp;lt;0.001). The mean number of ECT treatments was 2.5 for non-responders and 7.0 for responders (p=0.010). The mean number of ECT treatments did not differ significantly between remitters and non-remitters (7.2 vs 6.1, p=0.31). None of the other investigated potential predictors was statistically significantly associated with outcome.Conclusions: ECT is an effective treatment for cycloid psychosis. Future studies need to compare the outcome of ECT to that of other treatment strategies. Clinical implications: The high response rate with ECT indicates that cycloid psychosis is a clinically useful diagnosis.

  • 45.
    Homman, Lina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Department of Psychology, University of Sussex, Brighton, UK.
    Seglert, Jessica
    Department of Psychology, University of Sussex, Brighton, UK.
    Morgan, Michael J.
    Department of Psychology, University of Sussex, Brighton, UK; Norwegian Center for Addiction Research, University of Oslo, Oslo, Norway.
    An observational study on the sub-acute effects of mephedrone on mood, cognition, sleep and physical problems in regular mephedrone users2018In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 235, no 9, p. 2609-2618Article in journal (Refereed)
    Abstract [en]

    Mephedrone (4-methylmethcathinone; 4-MMC) is a novel recreational drug similar to methylenedioxymethamphetamine (MDMA) and amphetamine. Several adverse effects have been reported, but little is known about its sub-acute effects. To study sub-acute effects of mephedrone over a period of 9 days. Recreational mephedrone users were recruited and followed over a time period of 9 days. It was recorded whether participants consumed mephedrone or not within the period of testing; those who did were compared to those who did not. Forty-six regular mephedrone users (22 males, 24 females) participated, 21 participants voluntarily opted to consume mephedrone 1-3 days after baseline and 25 opted to abstain. Participants were assessed at baseline on a multitude of measures and provided daily reports on cognition, sleep, mood, physical problems, mephedrone cravings and substance use on each subsequent day of the study. The study controlled for psychopathology, sleep, past and current substance use, impulsivity and demographics. Those who consumed mephedrone reported persistent negative mood, physical problems and fatigue, compared to those who did not-after controlling for baseline group differences in sleep and subsequent alcohol and cannabis use. The results provide the first prospective evidence of the duration and extent of specific undesirable sub-acute effects of mephedrone in regular recreational users and indicate sub-acute effects of mephedrone on mood, fatigue and physical symptoms.

  • 46.
    Jedlinski, Adam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Garvin, Stina
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Johansson, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Edqvist, Per-Henrik
    Uppsala University, Uppsala, Sweden.
    Pontén, Fredrik
    Uppsala University, Uppsala, Sweden.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Cetuximab sensitivity of head and neck squamous cell carcinoma xenografts is associated with treatment-induced reduction of EGFR, pEGFR, and pSrc2017In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, no 9, p. 717-724Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to validate in vitro drug sensitivity testing of head and neck squamous cell carcinoma (HNSCC)cell lines in an in vivo xenograft model, and to identify treatment-induced changes in the EGFR signaling pathway that could be used as markersfor cetuximab treatment response.

    METHODS: The in vitro cetuximab sensitivity of two HNSCC cell lines, UT-SCC-14 and UTSCC-45, was assessed using a crystal violet assay. In order to determine the corresponding in vivo sensitivity, UT-SCC-14 and UT-SCC-45 xenografts were generated in female BALB/c (nu/nu) nude mice. Mice were given three injections of intraperitoneal cetuximab or PBS and the tumor volume was recorded continuously. The expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR (pEGFR), phosphorylated Src (pSrc), and Ki67 was investigated by immunohistochemistry.

    RESULTS: The treatment sensitive UT-SCC-14 cells were found to have an intrinsic cetuximab sensitivity (ICmabS) of 0.15 whereas the ICmabS of the insensitive cell line UT-SCC-45 was 0.78. The corresponding size ratio between untreated and cetuximab treated xenografts was 0.22 and 0.83 for UT-SCC-14 and UT-SCC-45, respectively. UT-SCC-14 cells had a higher baseline expression of pEGFR as compared to UT-SCC-45. Furthermore, in UT-SCC-14 xenografts there was a decrease in EGFR, pEGFR and pSrc upon cetuximab treatment. In contrast, a slight cetuximab-induced increase in EGFR, pEGFR and pSrc was observed in treatment-resistant UT-SCC-45 xenografts.

    CONCLUSIONS: The in vitro treatment sensitivity was reproduced in the in vivo model and cetuximab sensitivity was found to associate with a treatment-induced reduction in pEGFR and pSrc.

  • 47.
    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, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Yao, S.
    Karolinska Institute, Sweden.
    Kuja-Halkola, R.
    Karolinska Institute, Sweden.
    Bulik, C. M.
    Karolinska Institute, Sweden; University of North Carolina Chapel Hill, NC USA; University of North Carolina Chapel Hill, NC USA.
    Thornton, L. M.
    University of North Carolina Chapel Hill, NC USA.
    Bendtsen, Preben
    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 West Östergötland, Department of Medical Specialist in Motala.
    Marteinsdottir, Ina
    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 Psychiatry.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, H.
    Karolinska Institute, Sweden; Örebro University, Sweden.
    Genetic and environmental aspects in the association between attention-deficit hyperactivity disorder symptoms and binge-eating behavior in adults: a twin study2017In: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, Vol. 47, no 16, p. 2866-2878Article in journal (Refereed)
    Abstract [en]

    Background Prior research demonstrated that attention-deficit hyperactivity disorder (ADHD) is associated with binge-eating behavior, binge-eating disorder (BED), and bulimia nervosa (BN). The aim of this study was to investigate these associations in an adult twin population, and to determine the extent to which ADHD symptoms and binge-eating behavior share genetic and environmental factors. Methods We used self-reports of current ADHD symptoms and lifetime binge-eating behavior and associated characteristics from a sample of over 18 000 adult twins aged 20-46 years, from the population-based Swedish Twin Registry. Mixed-effects logistic regression was used to examine the association between ADHD and lifetime binge-eating behavior, BED, and BN. Structural equation modeling was used in 13 773 female twins to determine the relative contribution of genetic and environmental factors to the association between ADHD symptoms and binge-eating behavior in female adult twins. Results ADHD symptoms were significantly associated with lifetime binge-eating behavior, BED, and BN. The heritability estimate for current ADHD symptoms was 0.42 [95% confidence interval (CI) 0.41-0.44], and for lifetime binge-eating behavior 0.65 (95% CI 0.54-0.74). The genetic correlation was estimated as 0.35 (95% CI 0.25-0.46) and the covariance between ADHD and binge-eating behavior was primarily explained by genetic factors (91%). Non-shared environmental factors explained the remaining part of the covariance. Conclusions The association between adult ADHD symptoms and binge-eating behavior in females is largely explained by shared genetic risk factors.

  • 48.
    Jonsson, Emma H.
    et al.
    University of Gothenburg, Sweden.
    Bendas, Johanna
    Technical University of Dresden, Germany.
    Weidner, Kerstin
    Technical University of Dresden, Germany.
    Wessberg, Johan
    University of Gothenburg, Sweden.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. University of Gothenburg, Sweden.
    Backlund Wasling, Helena
    University of Gothenburg, Sweden.
    Croy, Ilona
    Technical University of Dresden, Germany.
    The relation between human hair follicle density and touch perception2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 2499Article in journal (Refereed)
    Abstract [en]

    Unmyelinated low threshold C-tactile fibers moderate pleasant aspects of touch. These fibers respond optimally to stroking stimulation of the skin with slow velocities (1-10 cm/s). Low threshold mechanoreceptors are arranged around hair follicles in rodent skin. If valid also in humans, hair follicle density (HFD) may relate to the perceived pleasantness of stroking tactile stimulation. We conducted two studies that examined the relation between HFD and affective touch perception in humans. In total, 138 healthy volunteers were stroked on the forearm and rated the pleasantness and intensity. Stimulation was performed by a robotic tactile stimulator delivering C-tactile optimal (1, 3, 10 cm/s) and non-optimal (0.1, 0.3, 30 cm/s) stroking velocities. Additionally, a measure of discriminative touch was applied in study 2. HFD of the same forearm was determined using the Cyanoacrylate Skin Stripping Method (CSSM), which we validated in a pretest. Women had higher HFD than men, which was explained by body size and weight. Furthermore, women rated affective touch stimuli as more pleasant and had higher tactile acuity. Depilation did not affect touch perception. A weak relationship was found between the C-tactile specific aspects of affective touch perception and HFD, and the hypothesis of HFD relating to pleasant aspects of stroking only received weak support.

  • 49.
    Jonsson, Emma H.
    et al.
    Univ Gothenburg, Sweden.
    Kotilahti, Kalle
    Aalto Univ, Finland.
    Heiskala, Juha
    Univ Helsinki, Finland.
    Wasling, Helena Backlund
    Univ Gothenburg, Sweden.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Gothenburg, Sweden.
    Croy, Ilona
    Tech Univ Dresden, Germany.
    Mustaniemi, Hanna
    Aalto Univ, Finland.
    Hiltunen, Petri
    Aalto Univ, Finland.
    Tuulari, Jetro J.
    Univ Turku, Finland.
    Scheinin, Noora M.
    Univ Turku, Finland; Turku Univ Hosp, Finland.
    Karlsson, Linnea
    Univ Turku, Finland; Turku Univ Hosp, Finland.
    Karlsson, Hasse
    Univ Turku, Finland; Turku Univ Hosp, Finland.
    Nissila, Ilkka
    Aalto Univ, Finland.
    Affective and non-affective touch evoke differential brain responses in 2-month-old infants2018In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 169, p. 162-171Article in journal (Refereed)
    Abstract [en]

    Caressing touch is an effective way to communicate emotions and to create social bonds. It is also one of the key mediators of early parental bonding. The caresses are generally thought to represent a social form of touching and indeed, slow, gentle brushing is encoded in specialized peripheral nerve fibers, the C-tactile (CT) afferents. In adults, areas such as the posterior insula and superior temporal sulcus are activated by affective, slow stroking touch but not by fast stroking stimulation. However, whether these areas are activated in infants, after social tactile stimulation, is unknown. In this study, we compared the total hemoglobin responses measured with diffuse optical tomography (DOT) in the left hemisphere following slow and fast stroking touch stimulation in 16 2-month-old infants. We compared slow stroking (optimal CT afferent stimulation) to fast stroking (non-optimal CT stimulation). Activated regions were delineated using two methods: one based on contrast between the two conditions, and the other based on voxel-based statistical significance of the difference between the two conditions. The first method showed a single activation cluster in the temporal cortex with center of gravity in the middle temporal gyrus where the total hemoglobin increased after the slow stroking relative to the fast stroking (p = 0.04 uncorrected). The second method revealed a cluster in the insula with an increase in total hemoglobin in the insular cortex in response to slow stroking relative to fast stroking (p = 0.0005 uncorrected; p = 0.04 corrected for multiple comparisons). These activation clusters encompass areas that are involved in processing of affective, slow stroking touch in the adult brain. We conclude that the infant brain shows a pronounced and adult-like response to slow stroking touch compared to fast stroking touch in the insular cortex but the expected response in the primary somatosensory cortex was not found at this age. The results imply that emotionally valent touch is encoded in the brain in adult-like manner already soon after birth and this suggests a potential for involvement of touch in bonding with the caretaker.

  • 50.
    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.
    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.
    Pribe, Gisela
    Department of Psychology, IKV, Lund University, Lund, Sweden.
    Fredlund, Cecilia
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Wadsby, Marie
    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.
    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.
    Similarities and differences in the functions of nonsuicidal self-injury (NSSI) and sex as self-injury (SASI)2017In: Journal of Suicide and Life-threatening Behaviour, ISSN 0363-0234, E-ISSN 1943-278XArticle in journal (Refereed)
    Abstract [en]

    Differences and similarities were studied in the functions of two different self-injurious behaviors (SIB): nonsuicidal self-injury (NSSI) and sex as self-injury (SASI). Based on type of SIB reported, adolescents were classified in one of three groups: NSSI only (n = 910), SASI only (n = 41), and both NSSI and SASI (n = 76). There was support for functional equivalence in the two forms of SIB, with automatic functions being most commonly endorsed in all three groups. There were also functional differences, with adolescents in the SASI only group reporting more social influence functions than those with NSSI only. Adolescents reporting both NSSI and SASI endorsed the highest number of functions for both behaviors. Clinical implications are discussed, emphasizing the need for emotion regulation skills.

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