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  • 1.
    Barchiesi, Riccardo
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Chanthongdee, Kanat
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Mahidol Univ, Thailand.
    Domi, Esi
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Gobbo, Francesco
    Univ Edinburgh, Scotland.
    Coppola, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Toivainen, Sanne
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Holm, Lovisa
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Gaëlle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Xu, Li
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Elect Sci & Technol China, Peoples R China.
    Augier, Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Barbier, Estelle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Stress-induced escalation of alcohol self-administration, anxiety-like behavior, and elevated amygdala Avp expression in a susceptible subpopulation of rats2021In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, Vol. 26, no 5, article id e13009Article in journal (Refereed)
    Abstract [en]

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

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  • 2.
    Kroll, Sara
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Mayo, Leah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Asratian, Anna
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience.
    Yngve, Adam
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Perini, Irene
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Negative self-evaluation induced by acute stress indexed using facial EMG2021In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 133, article id 105402Article in journal (Refereed)
    Abstract [en]

    Maladaptive stress responses are a key feature of several psychiatric disorders, but findings of stress effects on social behavior are inconsistent. Using a within-subject design, we investigated, in 35 healthy participants, the effects of acute stress on psychophysiological and behavioral responses during a simulated online social interaction task. Participants were exposed to established stress and non-stress exposure procedures in two separate sessions. During the task, participants liked or disliked pictures of other putative players and, similarly, saw their own picture being judged by others. After stress exposure, corrugator muscle activity (frowning) was significantly increased when participants saw their own picture while anticipating feedback from others. Consistently, zygomatic muscle activity (smiling) for self-evaluation was lower after stress than in the non-stress session. We found self-report of stress to be a significant predictor of corrugator activity in both sessions, indicating that higher levels of subjective stress overall were accompanied by increased negative self-evaluation. Surprisingly, no stress effects were found on behavioral measures of other-evaluation (i.e., percentage of dislikes to others), but corrugator response significantly predicted the percentage of dislikes during the stress session only. Overall, our findings suggest that stress increases negative self-evaluation as indexed by elevated corrugator activity. Furthermore, stress might sharpen the consistency between corrugator activity and negative evaluation of others. Our results indicate that negative self-evaluation might be a useful therapeutic target in patients with stressrelated psychiatric disorders. In this context, facial muscle activity may be an adequate biomarker for identifying stress-related differences in self-evaluation.

  • 3.
    Loseth, Guro Engvig
    et al.
    Univ Oslo, Norway.
    Eikemo, Marie
    Univ Oslo, Norway.
    Trostheim, Martin
    Univ Oslo, Norway; Oslo Univ Hosp, Norway.
    Meier, Isabell M.
    Univ Oslo, Norway; Oslo Univ Hosp, Norway.
    Bjornstad, Herman
    Univ Oslo, Norway; Univ Oslo, Norway.
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Pazmandi, Claudia
    Univ Oslo, Norway.
    Tangen, Vegard Wathne
    Univ Oslo, Norway.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Leknes, Siri
    Univ Oslo, Norway; Oslo Univ Hosp, Norway.
    Stress recovery with social support: A dyadic stress and support task2022In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 146, article id 105949Article in journal (Refereed)
    Abstract [en]

    How does social support bolster resilience? Here, we present a new dyadic paradigm to study causal mechanisms of acute and ecologically valid social support in the laboratory. The Dyadic Stress and Support Task (DSST) consists of a psychosocial stress phase and a recovery phase. During DSST stress, a pair of participants take turns to perform public speaking and mental arithmetic in front of a panel. Unable to see or touch each other, they witness each others performance and feedback. During DSST recovery, the pair either interact freely with each other for 5 min (social support condition) or interact separately with an experimenter (non-support condition). To establish the validity of the DSST, we tested 21 pairs of long-term close friends in a pilot study. Primary outcome measures were ratings of affective state and bodily arousal (VAS scales 0-100). Secondary outcome measures were heart rate and salivary cortisol. DSST stress successfully induced subjective Stress Activation, increased Negative Affect and decreased Positive Affect. We also observed increased heart rate and salivary cortisol. After DSST recovery, Stress Activation and Negative Affect ratings were reduced in both groups. Positive Affect was completely restored to pre-stress baseline levels in the Social support group, while remaining significantly lower in the Non-support group. The DSST successfully induced stress and negative affect and captured stress recovery in both groups. Free-form interaction with the friend enhanced recovery of affective state, supporting the validity of spontaneous interaction between friends as a model of social support.

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  • 4.
    Lundqvist, Carolina
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    General lifestyle factors explain young athletes mental health more than perceived coach autonomy support: a cross-sectional study on basketball players and gymnasts aged 10-222023In: BMJ OPEN SPORT & EXERCISE MEDICINE, ISSN 2055-7647, Vol. 9, no 3, article id e001648Article in journal (Refereed)
    Abstract [en]

    ObjectivesThis study described differences in lifestyle factors (sleeping problems/fatigue, pressure/activation), perceived coach autonomy support and indicators of mental health (well-being and poor general mental health) across various age groups (children & LE;12 years, youths 13-15 years, junior to senior & GE;16 years) and sports (basketball and gymnastics). Second, the relationships between lifestyle factors and mental health indicators were explored, hypothesising that the relationships would be mediated by perceived coach autonomy support.MethodsA cross-sectional study design was implemented by using an online survey which assessed lifestyle and environmental factors as well as mental health indicators. Participants were recruited through sports clubs in basketball and gymnastics. A total of 209 athletes (77 basketball players and 132 gymnasts) in the age range of 10-22 (median=13) years volunteered to complete the survey.ResultsSeparate two-way analyses of variance showed significant main effects for age group on sleeping problems/fatigue, sleep quantity, pressure/activation, well-being and poor general mental health, with higher scores reported for older age groups of athletes. Path analysis displayed sleeping problems/fatigue and pressure/activation to significantly affect decreased well-being and poor general mental health; however, the relationships were not mediated by perceived coach autonomy support.ConclusionLifestyle factors play a prominent role in mental health outcomes. Researchers studying athlete mental health should consider both general lifestyle and sports-related factors, considering developmental phases in the young athletes sporting context and overall life.

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  • 5.
    Lundqvist, Carolina
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, The Division of Cell and Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Wade, Tracey D
    Flinders University Institute for Mental Health and Wellbeing, South Australia, Australia.
    563 EP098 – Untangling the relationships between age, gender, type of sport, perfectionistic self-presentation, and motivation on body satisfaction among female and male athletes aged 10–222024In: British Journal of Sports Medicine, 2024, Vol. 58(suppl 2), p. A120-A120Conference paper (Other academic)
    Abstract [en]

    Background Body dissatisfaction is known as a robust predictor for eating pathology. Empirical knowledge about specific psychological mechanisms, beyond sports type, that can maintain or diminish female and male athletes’ body satisfaction is still sparse and research lack consistency. Prevention can decrease risk factors for eating pathology and protect athletes’ appreciation for the body and its functionality for continued and healthy sports participation.

    Objective To explore the relationships between age, gender, type of sport, perfectionistic self-presentation, and motivation on body satisfaction among young athletes in one lean sport (gymnastics) and one non-lean sport (basketball). Hypotheses: Age, gender, and sport type are related to body satisfaction. A high autonomous motivation is positively related to body satisfaction while perfectionistic self-presentation displays a negative relationship.

    Design Cross-sectional.

    Setting Recreational to national elite level.

    Participants A total of 209 athletes (basketball players n=77; gymnasts n=132; age range: 10–22) were recruited and 200 (females: n=157; males: n=43) were included in the analyses after data screening.

    Assessment of Risk Factors Questionnaires were completed electronically and assessed demographic information (e.g., age, self-assigned gender), motivation (Behavioral Regulation in Sport Questionnaire), perfectionistic self-presentation (Perfectionistic Self-Presentation Scale – Junior Form) and body satisfaction (Body Appreciation Scale-2).

    Main Outcome Measurements Body satisfaction (dependent variable).

    Results Stepwise multiple regressions with bootstrapping showed age, self-assigned gender, and perfectionistic self-presentation (non-display of imperfection) to significantly predict body satisfaction (p<.05). Path analysis showed a significant relationship between age and body satisfaction (standardized coefficient: -.23) which was partially mediated by non-display of imperfection (p<.05). A moderated mediation analysis showed that this relationship was not moderated by gender.

    Conclusions Body satisfaction prevention should target perfectionistic self-presentation tendencies among female and male athletes. Further research is warranted to investigate if non-display of imperfection is a prominent perfectionistic self-presentation facet among athletes across gender, sports and competition levels.

  • 6.
    Lundqvist, Carolina
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Kolbeinsson, Örn
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Asratian, Anna
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, The Division of Cell and Neurobiology.
    Wade, Tracey D
    Flinders University Institute for Mental Health and Wellbeing, South Australia, Australia.
    Untangling the relationships between age, gender, type of sport, perfectionistic self-presentation, and motivation on body satisfaction.: A cross-sectional study on aesthetic and non-aesthetic female and male athletes aged 10 to 22.2024In: BMJ Open Sport & Exercise Medicine, ISSN 2055-7647Article in journal (Refereed)
    Abstract [en]

    Objectives: To explore the relationships between age, gender, type of sport, perfectionistic self-presentation and motivation on body satisfaction among young athletes in one aesthetic sport (gymnastics) and one non-aesthetic sport (basketball). The study hypothesise that (1) age, gender, and type of sport (aesthetic or non-aesthetic) will predict body satisfaction scores, (2) autonomous motivation will positively relate to body satisfaction, and (3) perfectionistic self-presentation will negatively relate to body satisfaction.

    Design: Cross-sectional. 

    Method: 209 athletes (132 gymnasts and 77 basketball players) aged 10-22 (median=13 years) were recruited. After data screening, 200 athletes were included in analyses (females: n=155; males: n=45). Participants completed an online survey which assessed demographic information, athlete motivation (Behavioral Regulation in Sport Questionnaire), perfectionistic self-presentation (Perfectionistic Self-Presentation Scale – Junior Form) and body satisfaction (Body Appreciation Scale-2). 

    Results: Hierarchical multiple regression showed age, self-assigned gender, and two facets of perfectionism (perfectionistic self-presentation and non-disclosure of imperfection) to predict reported levels of body satisfaction significantly. Subsequently, adding motivational variables did not improve the model. A moderation analysis showed that the relationship between non-disclosure of imperfection and body satisfaction was significantly moderated by gender. 

    Conclusions: Two facets of perfectionism were associated with reported body satisfaction. Additionally, the relationship between non-disclosure of imperfection and body satisfaction appears to differ between female and male athletes. Researchers should move beyond sport types and identify factors (e.g., perfectionistic self-presentation) at the individual and environmental level that can protect young athletes’ body satisfaction.

  • 7.
    Mayo, Leah
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Lindé, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Morena, Maria
    Cummings Scool Med, Canada; Univ Calgary, Canada; Univ Calgary, Canada.
    Haataja, Roosa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Hammar, Valter
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Gaëlle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Hill, Matthew N.
    Cummings Scool Med, Canada; Cummings Scool Med, Canada; Univ Calgary, Canada; Univ Calgary, Canada.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial2020In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 87, no 6, p. 538-547Article in journal (Refereed)
    Abstract [en]

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

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  • 8.
    Mayo, Leah M.
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Lindé, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Holm, Lovisa
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Nätt, Daniel
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Gaëlle
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Stensson, Niclas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Vecchiarelli, Haley A.
    Hotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Canada.
    Balsevich, Georgia
    Hotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Canada.
    Aukema, Robert J.
    Hotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Canada.
    Ghafouri, Bijar
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine.
    Spagnolo, Primavera A.
    National Institute on Alcohol Abuse and Alcoholism and National Institute of Neurological Disorders and Stroke, NIH, Bethesda, USA.
    Lee, Francis S.
    Institute for Developmental Psychobiology, Weill Cornell Medical College of Cornell University, New York, USA.
    Hill, Matthew N.
    Hotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Canada.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice2020In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 25, no 5, p. 993-1005Article in journal (Refereed)
    Abstract [en]

    Post-traumatic stress disorder (PTSD) is a common, debilitating condition with limited treatment options. Extinction of fear memories through prolonged exposure therapy, the primary evidence-based behavioral treatment for PTSD, has only partial efficacy. In mice, pharmacological inhibition of fatty acid amide hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear extinction, suggesting that FAAH inhibitors may aid fear extinction-based treatments. A human FAAH 385C-greater thanA substitution encodes an FAAH enzyme with reduced catabolic efficacy. Individuals homozygous for the FAAH 385A allele may therefore offer a genetic model to evaluate the impact of elevations in AEA signaling in humans, helping to inform whether FAAH inhibitors have the potential to facilitate fear extinction therapy for PTSD. To overcome the challenge posed by low frequency of the AA genotype (appr. 5%), we prospectively genotyped 423 individuals to examine the balanced groups of CC, AC, and AA individuals (n = 25/group). Consistent with its loss-of-function nature, the A allele was dose dependently associated with elevated basal AEA levels, facilitated fear extinction, and enhanced the extinction recall. Moreover, the A-allele homozygotes were protected against stress-induced decreases in AEA and negative emotional consequences of stress. In a humanized mouse model, AA homozygous mice were similarly protected against stress-induced decreases in AEA, both in the periphery, and also in the amygdala and prefrontal cortex, brain structures critically involved in fear extinction and regulation of stress responses. Collectively, these data suggest that AEA signaling can temper aspects of the stress response and that FAAH inhibition may aid the treatment for stress-related psychiatric disorders, such as PTSD.

  • 9.
    Paul, Elisabeth
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Schwieler, Lilly
    Karolinska Inst, Sweden.
    Erhardt, Sophie
    Karolinska Inst, Sweden.
    Boda, Sandra
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Trepci, Ada
    Karolinska Inst, Sweden.
    Kämpe, Robin
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Holm, Lovisa
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Yngve, Adam
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Dantzer, Robert
    Univ Texas MD Anderson Canc Ctr, TX 77030 USA.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Hamilton, Paul J.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Samuelsson, Martin
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Peripheral and central kynurenine pathway abnormalities in major depression2022In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 101, p. 136-145Article in journal (Refereed)
    Abstract [en]

    Considerable data relate major depressive disorder (MDD) with aberrant immune system functioning. Pro inflammatory cytokines facilitate metabolism of tryptophan along the kynurenine pathway (KP) putatively resulting in reduced neuroprotective and increased neurotoxic KP metabolites in MDD, in addition to modulating metabolic and immune function. This central nervous system hypothesis has, however, only been tested in the periphery. Here, we measured KP-metabolite levels in both plasma and cerebrospinal fluid (CSF) of depressed patients (n = 63/36 respectively) and healthy controls (n = 48/33). Further, we assessed the relation between KP abnormalities and brain-structure volumes, as well as body mass index (BMI), an index of metabolic disturbance associated with atypical depression. Plasma levels of picolinic acid (PIC), the kynurenic/quinolinic acid ratio (KYNA/QUIN), and PIC/QUIN were lower in MDD, but QUIN levels were increased. In the CSF, we found lower PIC in MDD. Confirming previous work, MDD patients had lower hippocampal, and amygdalar volumes. Hippocampal and amygdalar volumes were correlated positively with plasma KYNA/QUIN ratio in MDD patients. BMI was increased in the MDD group relative to the control group. Moreover, BMI was inversely correlated with plasma and CSF PIC and PIC/QUIN, and positively correlated with plasma QUIN levels in MDD. Our results partially confirm previous peripheral KP findings and extend them to the CSF in MDD. We present the novel finding that abnormalities in KP metabolites are related to metabolic disturbances in depression, but the relation between KP metabolites and depression-associated brain atrophy might not be as direct as previously hypothesized.

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  • 10.
    Perini, Irene
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Mayo, Leah M.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Johansson Capusan, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Paul, Elisabeth
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Yngve, Adam
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Kämpe, Robin
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gauffin, Emelie
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Mazurka, Raegan Mary Rose
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Stensson, Niclas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Hamilton, J. Paul
    Univ Bergen, Norway.
    Kastbom, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Gustafsson, Per A
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation2023In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, no 6, p. 2563-2571Article in journal (Refereed)
    Abstract [en]

    Childhood maltreatment (CM) is a risk factor for substance use disorders (SUD) in adulthood. Understanding the mechanisms by which people are susceptible or resilient to developing SUD after exposure to CM is important for improving intervention. This case-control study investigated the impact of prospectively assessed CM on biomarkers of endocannabinoid function and emotion regulation in relation to the susceptibility or resilience to developing SUD. Four groups were defined across the dimensions of CM and lifetime SUD (N = 101 in total). After screening, participants completed two experimental sessions on separate days, aimed at assessing the behavioral, physiological, and neural mechanisms involved in emotion regulation. In the first session, participants engaged in tasks assessing biochemical (i.e., cortisol, endocannabinoids), behavioral, and psychophysiological indices of stress and affective reactivity. During the second session, the behavioral and brain mechanisms associated with emotion regulation and negative affect were investigated using magnetic resonance imaging. CM-exposed adults who did not develop SUD, operationally defined as resilient to developing SUD, had higher peripheral levels of the endocannabinoid anandamide at baseline and during stress exposure, compared to controls. Similarly, this group had increased activity in salience and emotion regulation regions in task-based measures of emotion regulation compared to controls, and CM-exposed adults with lifetime SUD. At rest, the resilient group also showed significantly greater negative connectivity between ventromedial prefrontal cortex and anterior insula compared to controls and CM-exposed adults with lifetime SUD. Collectively, these peripheral and central findings point to mechanisms of potential resilience to developing SUD after documented CM exposure.

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  • 11.
    Pietrzak, Michal
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Yngve, Adam
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hamilton, Paul J.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Gauffin, Emelie
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Löfberg, Andreas
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Gustavson, Sarah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Persson, Emil
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Johansson Capusan, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Leggio, Lorenzo
    Natl Inst Drug Abuse Intramural Res Program, MD 21224 USA; Natl Inst Alcohol Abuse & Alcoholism, MD 21224 USA.
    Perini, Irene
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tinghög, Gustav
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Heilig, Markus
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Böhme, Rebecca
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ghrelin decreases sensitivity to negative feedback and increases prediction-error related caudate activity in humans, a randomized controlled trial2024In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 49, p. 1042-1049Article in journal (Refereed)
    Abstract [en]

    The stomach-derived hormone ghrelin plays not only a role in feeding, starvation, and survival, but it has been suggested to also be involved in the stress response, in neuropsychiatric conditions, and in alcohol and drug use disorders. Mechanisms related to reward processing might mediate ghrelin's broader effects on complex behaviors, as indicated by animal studies and mostly correlative human studies. Here, using a within-subject double-blind placebo-controlled design with intravenous ghrelin infusion in healthy volunteers (n = 30), we tested whether ghrelin alters sensitivity to reward and punishment in a reward learning task. Parameters were derived from a computational model of participants' task behavior. The reversal learning task with monetary rewards was performed during functional brain imaging to investigate ghrelin effects on brain signals related to reward prediction errors. Compared to placebo, ghrelin decreased punishment sensitivity (t = -2.448, p = 0.021), while reward sensitivity was unaltered (t = 0.8, p = 0.43). We furthermore found increased prediction-error related activity in the dorsal striatum during ghrelin administration (region of interest analysis: t-values >= 4.21, p-values <= 0.044). Our results support a role for ghrelin in reward processing that extends beyond food-related rewards. Reduced sensitivity to negative outcomes and increased processing of prediction errors may be beneficial for food foraging when hungry but could also relate to increased risk taking and impulsivity in the broader context of addictive behaviors.

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  • 12.
    Pietrzak, Michal
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Yngve, Adam
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hamilton, Paul
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Univ Bergen, Norway.
    Kämpe, Robin
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Böhme, Rebecca
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Asratian, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gauffin, Emelie
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Löfberg, Andreas
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gustavsson, Sarah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Persson, Emil
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Johansson Capusan, Andrea
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
    Leggio, Lorenzo
    Natl Inst Drug Abuse Intramural Res Program, MD USA; Natl Inst Alcohol Abuse & Alcoholism, MD USA.
    Perini, Irene
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tinghög, Gustav
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health.
    Heilig, Markus
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    A randomized controlled experimental medicine study of ghrelin in value-based decision making2023In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 133, no 12, article id e168260Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. The stomach-derived hormone ghrelin stimulates appetite, but the ghrelin receptor is also expressed in brain circuits involved in motivation and reward. We examined ghrelin effects on decision making beyond food or drug reward using monetary rewards. METHODS. Thirty participants (50% women and 50% men) underwent 2 fMRI scans while receiving i.v. ghrelin or saline in a randomized counterbalanced order. RESULTS. Striatal representations of reward anticipation were unaffected by ghrelin, while activity during anticipation of losses was attenuated. Temporal discounting rates of monetary reward were lower overall in the ghrelin condition, an effect driven by women. Discounting rates were inversely correlated with neural activity in a large cluster within the left parietal lobule that included the angular gyrus. Activity in an overlapping cluster was related to behavioral choices and was suppressed by ghrelin. CONCLUSION. This is, to our knowledge, the first human study to extend the understanding of ghrelins significance beyond the canonical feeding domain or in relation to addictive substances. Contrary to our hypothesis, we found that ghrelin did not affect sensitivity to monetary reward anticipation, but rather resulted in attenuated loss aversion and lower discounting rates for these rewards. Ghrelin may cause a motivational shift toward caloric reward rather than globally promoting the value of reward. TRIAL REGISTRATION. EudraCT 2018-004829-82.

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