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  • 1.
    Aho, Nikolas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gren Landell, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    The Prevalence of Potentially Victimizing Events, Poly-Victimization, and Its Association to Sociodemographic Factors: A Swedish Youth Survey2016In: Journal of Interpersonal Violence, ISSN 0886-2605, E-ISSN 1552-6518, Vol. 31, no 4, p. 620-651Article in journal (Refereed)
    Abstract [en]

    Studying the extent to which children are exposed to victimizing events is important to fully understand the effect of such exposure in shaping them as adults. The aim of this study was to use self-report by adolescents to measure the prevalence of victimizing events and of poly-victimization. A representative sample of 5,960 students (aged 17) from high schools in Sweden was given the self-administrated version of the Juvenile Victimization Questionnaire (JVQ) along with questions concerning gender, birthplace, parents birthplace and employment, residence, educational program, and municipality size. The results show that 84.1% (83.0% young men and 85.2% young women) of the students had experienced victimization during their lifetime, and 10.3% were categorized as poly-victims (8.1% young men and 12.5% young women; OR = 1.62, 95% confidence interval [CI] = [1.35, 1.94]). Adolescents living with both parents were at lower risk of any form of victimization for both genders, while females were at higher risk of maltreatment, peer victimization, and, most significantly, sexual victimization. In conclusion, the vast majority of young people have been victimized during their lifetime. A greater awareness of the impact of these victimizing events on children and adolescents is important as a basis for providing a safer milieu and establishing better interventions, especially for those that have been victimized on multiple occasions. The high-exposure group was determined by using 10 events as a cutoff. Findings on this group corresponded with findings in other international studies regarding distribution, elevated risk for females, and the possibility of limiting the effects of victimization by modifying living conditions.

  • 2.
    Augier, Eric
    et al.
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Dulman, Russell S.
    NIAAA, MD USA.
    Rauffenbart, Caroline
    NIAAA, MD USA.
    Augier, Gaelle
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Cross, Alan J.
    AstraZeneca Neurosci, MA USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    The mGluR2 Positive Allosteric Modulator, AZD8529, and Cue-Induced Relapse to Alcohol Seeking in Rats2016In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 41, no 12, p. 2932-2940Article in journal (Refereed)
    Abstract [en]

    Group II metabotropic glutamate receptors (mGluR2 and mGluR3) may control relapse of alcohol seeking, but previously available Group II agonists were unable to discriminate between mGluR2 and mGluR3. Here we use AZD8529, a novel positive allosteric mGluR2 modulator, to determine the role of this receptor for alcohol-related behaviors in rats. We assessed the effects of AZD8529 (20 and 40 mg/kg s.c.) on male Wistar rats trained to self-administer 20% alcohol and determined the effects of AZD8529 on self-administration, as well as stress-induced and cue-induced reinstatement of alcohol seeking. The on-target nature of findings was evaluated in Indiana P-rats, a line recently shown to carry a mutation that disrupts the gene encoding mGluR2. The behavioral specificity of AZD8529 was assessed using self-administration of 0.2% saccharin and locomotor activity tests. AZD8529 marginally decreased alcohol self-administration at doses that neither affected 0.2% saccharin self-administration nor locomotor activity. More importantly, cue- but not stress-induced alcohol seeking was blocked by the mGluR2 positive allosteric modulator. This effect of AZD8529 was completely absent in P rats lacking functional mGluR2s, demonstrating the receptor specificity of this effect. Our findings provide evidence fora causal role of mGluR2 in cue induced relapse to alcohol seeking. They contribute support for the notion that positive allosteric modulators of mGluR2 block relapse-like behavior across different drug categories.

  • 3.
    Aziz, Abdul Maruf Asif
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Brothers, Shaun
    University of Miami Health System, University of Miami, Miami, USA.
    Sartor, Gregory
    University of Miami Health System, University of Miami, Miami, USA.
    Holm, Lovisa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Wahlestedt, Claes
    University of Miami Health System, University of Miami, Miami, USA.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    The nociceptin/orphanin FQ receptor agonist SR-8993 as a candidate therapeutic for alcohol use disorders: validation in rat models2016In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 19-20, p. 3553-3563Article in journal (Refereed)
    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.

  • 4.
    Backlund, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Feedback-informerad terapi på familjerådgivningen - Leder det till förbättring?2016Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The following study is about feedback informed treatment in family councelling. The purpose was to measure the couples experienced change in life satisfaction, to see if treatment sessions of family councelling makes a difference and change according to the estimation instruments ORS and SRS and is consistent with the estimate of the atmosphere in the couple´s relationship/family atmosphere and if there were any gender differences. The study group included 29 couples who sought help at the Family councelling in southern Dalarna, Mora and Linköping during the period of January 2016 to May 2016. The couples filled in the instrument ORS (measuring change) at the beginning of each session and SRS (measuring alliance) at the end of each session. The family councellor used the received feedback and corrected treatment accordingly. In the first and third session the couples filled in the "Family climate" instrument. The outcome after three sessions showed a small improvement in the life satisfaction for both men and women which were consistent with the estimate of the atmosphere and the climate in the family. The vicinity improved and chaos decreased.

  • 5.
    Bergamino, Maurizio
    et al.
    Laureate Institute Brain Research, OK, USA.
    Pasternak, Ofer
    Harvard University, MA, USA.
    Farmer, Madison
    Laureate Institute Brain Research, OK, USA.
    Shenton, Martha E.
    Harvard University, MA, USA; VA Boston Healthcare Syst, MA USA.
    Hamilton, Paul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Laureate Institute Brain Research, OK, USA.
    Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression2016In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 10, p. 336-342Article in journal (Refereed)
    Abstract [en]

    Diffusion tensor imaging (DTI) holds promise for developing our understanding of white-matter pathology in major depressive disorder (MDD). Variable findings in DTI-based investigations ofMDD, however, have thwarted development of this literature. Effects of extra-cellular free-water on the sensitivity of DTI metrics could account for some of this inconsistency. Here we investigated whether applying a free-water correction algorithm to DTI data could improve the sensitivity to detect clinical effects using DTI metrics. Only after applying this correction, we found: a) significantly decreased fractional anisotropy and axial diffusivity (AD) in the left inferior frontooccipital fasciculus (IFOF) in MDD; and b) increased self-reported stress that significantly correlated with decreased IFOF AD in depression. We estimated and confirmed the robustness of differences observed between free-water corrected and uncorrected approaches using bootstrapping. We conclude that applying a free-water correction to DTI data increases the sensitivity of DTI-based metrics to detect clinical effects in MDD. (C) 2015 The Authors. Published by Elsevier Inc.

  • 6.
    Bernardi, R. E.
    et al.
    Heidelberg University, Germany.
    Zohsel, K.
    Heidelberg University, Germany.
    Hirth, N.
    Heidelberg University, Germany.
    Treutlein, J.
    Heidelberg University, Germany.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Laucht, M.
    Heidelberg University, Germany.
    Spanagel, R.
    Heidelberg University, Germany.
    Sommer, W. H.
    Heidelberg University, Germany.
    A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology2016In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 6, no e861Article in journal (Refereed)
    Abstract [en]

    It has been proposed that vulnerability to nicotine addiction is moderated by variation at the mu-opioid receptor locus (OPRM1), but results from human studies vary and prospective studies based on genotype are lacking. We have developed a humanized mouse model of the most common functional OPRM1 polymorphism rs1799971_A4G (A118G). Here we use this model system together with a cohort of German youth to examine the role of the OPRM1 A118G variation on nicotine reward. Nicotine reinforcement was examined in the humanized mouse model using i.v. self-administration. Male (n = 17) and female (n = 26) mice homozygous either for the major human A allele (AA) or the minor G allele (GG) underwent eight daily 2 h sessions of nicotine self-administration. Furthermore, male (n = 104) and female (n = 118) subjects homozygous for the A allele or carrying the G allele from the Mannheim Study of Children at Risk were evaluated for pleasurable and unpleasant experiences during their initial smoking experience. A significant sex-by-genotype effect was observed for nicotine self-administration. Male 118GG mice demonstrated higher nicotine intake than male 118AA mice, suggesting increased nicotine reinforcement. In contrast, there was no genotype effect in female mice. Human male G allele carriers reported increased pleasurable effects from their first smoking experience, as compared to male homozygous A, female G and female homozygous A allele carriers. The 118G allele appears to confer greater sensitivity to nicotine reinforcement in males, but not females.

  • 7.
    Case, Laura K
    et al.
    National Center for Complementary and Integrative Health, NIH , Bethesda, Maryland 20892, USA.
    Čeko, Marta
    National Center for Complementary and Integrative Health, NIH , Bethesda, Maryland 20892, USA.
    Gracely, John L
    National Center for Complementary and Integrative Health, NIH , Bethesda, Maryland 20892, USA.
    Richards, Emily A
    National Center for Complementary and Integrative Health, NIH , Bethesda, Maryland 20892, USA.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Bushnell, M Catherine
    National Center for Complementary and Integrative Health, NIH , Bethesda, Maryland 20892, USA.
    Touch Perception Altered by Chronic Pain and by Opioid Blockade.2016In: eNeuro, ISSN 2373-2822, Vol. 3, no 1Article in journal (Refereed)
    Abstract [en]

    Touch plays a significant role in human social behavior and social communication, and its rewarding nature has been suggested to involve opioids. Opioid blockade in monkeys leads to increased solicitation and receipt of grooming, suggesting heightened enjoyment of touch. We sought to study the role of endogenous opioids in perception of affective touch in healthy adults and in patients with fibromyalgia, a chronic pain condition shown to involve reduced opioid receptor availability. The pleasantness of touch has been linked to the activation of C-tactile fibers, which respond maximally to slow gentle touch and correlate with ratings of pleasantness. We administered naloxone to patients and healthy controls to directly observe the consequences of µ-opioid blockade on the perceived pleasantness and intensity of touch. We found that at baseline chronic pain patients showed a blunted distinction between slow and fast brushing for both intensity and pleasantness, suggesting reduced C-tactile touch processing. In addition, we found a differential effect of opioid blockade on touch perception in healthy subjects and pain patients. In healthy individuals, opioid blockade showed a trend toward increased ratings of touch pleasantness, while in chronic pain patients it significantly decreased ratings of touch intensity. Further, in healthy individuals, naloxone-induced increase in touch pleasantness was associated with naloxone-induced decreased preference for slow touch, suggesting a possible effect of opioid levels on processing of C-tactile fiber input. These findings suggest a role for endogenous opioids in touch processing, and provide further evidence for altered opioid functioning in chronic pain patients.

  • 8.
    Cavallo, Joel S.
    et al.
    University of Chicago, IL 60637 USA.
    Mayo, Leah
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    de Wit, Harriet
    University of Chicago, IL 60637 USA.
    Acquisition of Conditioning between Methamphetamine and Cues in Healthy Humans2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 8, p. e0161541-Article in journal (Refereed)
    Abstract [en]

    Environmental stimuli repeatedly paired with drugs of abuse can elicit conditioned responses that are thought to promote future drug seeking. We recently showed that healthy volunteers acquired conditioned responses to auditory and visual stimuli after just two pairings with methamphetamine (MA, 20 mg, oral). This study extended these findings by systematically varying the number of drug-stimuli pairings. We expected that more pairings would result in stronger conditioning. Three groups of healthy adults were randomly assigned to receive 1, 2 or 4 pairings (Groups P1, P2 and P4, Ns = 13, 16, 16, respectively) of an auditory-visual stimulus with MA, and another stimulus with placebo (PBO). Drug-cue pairings were administered in an alternating, counterbalanced order, under double-blind conditions, during 4 hr sessions. MA produced prototypic subjective effects (mood, ratings of drug effects) and alterations in physiology (heart rate, blood pressure). Although subjects did not exhibit increased behavioral preference for, or emotional reactivity to, the MA-paired cue after conditioning, they did exhibit an increase in attentional bias (initial gaze) toward the drug-paired stimulus. Further, subjects who had four pairings reported " liking" the MApaired cue more than the PBO cue after conditioning. Thus, the number of drug-stimulus pairings, varying from one to four, had only modest effects on the strength of conditioned responses. Further studies investigating the parameters under which drug conditioning occurs will help to identify risk factors for developing drug abuse, and provide new treatment strategies.

  • 9.
    Croy, Ilona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. University of Gothenburg, Sweden; Technical University of Dresden, Germany.
    Drechsler, Edda
    Technical University of Dresden, Germany.
    Hamilton, Paul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Hummel, Thomas
    Technical University of Dresden, Germany.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. University of Gothenburg, Sweden.
    Olfactory modulation of affective touch processing - A neurophysiological investigation2016In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 135, p. 135-141Article in journal (Refereed)
    Abstract [en]

    Touch can be highly emotional, and depending on the environment, it can be perceived as pleasant and comforting or disgusting and dangerous. Here, we studied the impact of context on the processing of tactile stimuli using a functional magnetic resonance imaging (fMRI) paradigm. This was achieved by embedding tactile stimulation in a variable olfactory environment. Twenty people were scanned with BOLD fMRI while receiving the following stimulus blocks: Slow stroking Touch, Civette odor (feces like), Rose odor, Touch + Civette, and Touch + Rose. Ratings of pleasantness and intensity of tactile stimuli and ratings of disgust and intensity of olfactory stimuli were collected. The impact of the olfactory context on the processing of touch was studied using covariance analyses. Coupling between olfactory processing and somatosensory processing areas was assessed with psychophysiological interaction analysis (PPI). A subjectively disgusting olfactory environment significantly reduced the perceived pleasantness of touch. The touch fMRI activation in the secondary somatosensory cortex, operculum 1 (OP1), was positively correlated with the disgust towards the odors. Decreased pleasantness of touch was related to decreased posterior insula activity. PPI analysis revealed a significant interaction between the OP1, posterior insula, and regions processing the disgust of odors (orbitofrontal cortex and amygdala). We conclude that the disgust evaluation of the olfactory environment moderates neural reactivity in somatosensory regions by upregulation of the OP1 and downregulation of the posterior insula. This adaptive regulation of affective touch processing may facilitate adaptive reaction to a potentially harmful stimulus. (C) 2016 Elsevier Inc. All rights reserved.

  • 10.
    Croy, Ilona
    et al.
    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.
    Geide, Helen
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Paulus, Martin
    Laureate Institute Brain Research, OK USA.
    Weidner, Kerstin
    Technical University of Dresden, Germany.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Affective touch awareness in mental health and disease relates to autistic traits - An explorative neurophysiological investigation2016In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 245, p. 491-496Article in journal (Refereed)
    Abstract [en]

    Affective touch is important for social interaction within families and groups and there is evidence that unmyelinated C tactile fibers are involved in this process. Individuals with autism spectrum disorders show alterations in the perception and processing of affective touch. sThus, we hypothesized that affective touch awareness based on C tactile fiber activation is impaired in individuals with high levels of autistic trait. The pleasantness perception of optimal and suboptimal C tactile stimuli was tested in an explorative study in 70 patients recruited from an outpatient psychotherapy clinic and 69 healthy comparison subjects. All participants completed questionnaires about autistic traits, depressive symptomatology, childhood maltreatment, and about the daily amount of touch. Relative to comparison subjects, patients reported engaging in touch less frequently in daily life and rated touch less pleasant. Reduced valence ratings of touch were explained by childhood maltreatment but not by any particular disorder or depression severity. Among all tested variables, the affective touch awareness correlated with autistic traits only - in patients as well as in comparison subjects. Taken together, individuals with mental health issues have a lower baseline of expression and reception of affective touch. Autistic traits and childhood maltreatment modulate the experience of affective touch. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 11.
    Croy, Ilona
    et al.
    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.
    Luong, A.
    Sahlgrens University Hospital, Sweden.
    Triscoli, C.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Sahlgrens University Hospital, Sweden.
    Hofmann, E.
    Technical University of Dresden, Germany.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sailer, U.
    University of Gothenburg, Sweden.
    Interpersonal stroking touch is targeted to C tactile afferent activation2016In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 297, p. 37-40Article in journal (Refereed)
    Abstract [en]

    C tactile fibers are a specialized group of fibers innervating the non-glabrous skin that are tuned to light gentle stroking applied with velocities between 1 and 10 cm/s. Those fibers add to the sensation of interpersonal caressing and pleasant touch. It is unclear whether people spontaneously apply touch that is tuned to optimally activate those fibers. This was investigated in three studies. In study one, 45 participants (21.8 +/- 2.3 years, 24 women) were asked to stroke an artificial arm. In study two, 32 participants (28.3 +/- 8.7years, 16 women) were asked to stroke their partner. In study three, 11 parents (29.4 +/- 5.7years, 6 women) were asked to stroke their babies. Stroking velocity was tracked in all conditions. Stroking velocities were significantly slower in the partner touch and baby touch condition than in the artificial arm condition and all of the participants stroking their partner or baby used velocities that can activate C tactile fibers. We conclude that human social stroking is optimized for C tactile stimulation. (C) 2015 Elsevier B.V. All rights reserved.

  • 12.
    Davidovic, Monika
    et al.
    University of Gothenburg, Sweden.
    Jonsson, Emma H.
    University of Gothenburg, Sweden.
    Olausson, Håkan
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Björnsdotter Åberg, Malin
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. University of Gothenburg, Sweden.
    Posterior Superior Temporal Sulcus Responses Predict Perceived Pleasantness of Skin Stroking2016In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 10, no 432Article in journal (Refereed)
    Abstract [en]

    Love and affection is expressed through a range of physically intimate gestures, including caresses. Recent studies suggest that posterior temporal lobe areas typically associated with visual processing of social cues also respond to interpersonal touch. Here, we asked whether these areas are selective to caress-like skin stroking. We collected functional magnetic resonance imaging data from 23 healthy participants and compared brain responses to skin stroking and vibration. We did not find any significant differences between stroking and vibration in the posterior temporal lobe; however, right posterior superior temporal sulcus (pSTS) responses predicted healthy participants perceived pleasantness of skin stroking, but not vibration. These findings link right pSTS responses to individual variability in perceived pleasantness of caress-like tactile stimuli. We speculate that the right pSTS may play a role in the translation of tactile stimuli into positively valenced, socially relevant interpersonal touch and that this system may be affected in disorders associated with impaired attachment.

  • 13.
    Domi, Esi
    et al.
    University of Camerino, Italy.
    Uhrig, Stefanie
    Heidelberg University, Germany.
    Soverchia, Laura
    University of Camerino, Italy.
    Spanagel, Rainer
    Heidelberg University, Germany.
    Hansson, Anita C.
    Heidelberg University, Germany.
    Barbier, Estelle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Ciccocioppo, Roberto
    University of Camerino, Italy.
    Ubaldi, Massimo
    University of Camerino, Italy.
    Genetic Deletion of Neuronal PPAR gamma Enhances the Emotional Response to Acute Stress and Exacerbates Anxiety: An Effect Reversed by Rescue of Amygdala PPAR gamma Function2016In: JOURNAL OF NEUROSCIENCE, ISSN 0270-6474, Vol. 36, no 50, p. 12611-12623Article in journal (Refereed)
    Abstract [en]

    PPAR gamma is one of the three isoforms of the Peroxisome Proliferator-Activated Receptors (PPARs). PPAR gamma is activated by thiazolidinediones such as pioglitazone and is targeted to treat insulin resistance. PPAR gamma is densely expressed in brain areas involved in regulation of motivational and emotional processes. Here, we investigated the role of PPAR gamma in the brain and explored its role in anxiety and stress responses in mice. The results show that stimulation of PPAR gamma by pioglitazone did not affect basal anxiety, but fully prevented the anxiogenic effect of acute stress. Using mice with genetic ablation of neuronal PPAR gamma (PPAR gamma(NestinCre)), we demonstrated that a lack of receptors, specifically in neurons, exacerbated basal anxiety and enhanced stress sensitivity. The administration of GW9662, a selective PPAR gamma antagonist, elicited a marked anxiogenic response in PPAR gamma wild-type (WT), but not in PPAR gamma(NestinCre) knock-out (KO) mice. Using c-Fos immunohistochemistry, we observed that acute stress exposure resulted in a different pattern of neuronal activation in the amygdala (AMY) and the hippocampus (HIPP) of PPAR gamma(NestinCre) KO mice compared with WT mice. No differences were found between WT and KO mice in hypothalamic regions responsible for hormonal response to stress or in blood corticosterone levels. Microinjection of pioglitazone into the AMY, but not into the HIPP, abolished the anxiogenic response elicited by acute stress. Results also showed that, in both regions, PPAR gamma colocalizes with GABAergic cells. These findings demonstrate that neuronal PPAR gamma is involved the regulation of the stress response and that the AMY is a key substrate for the anxiolytic effect of PPAR gamma

  • 14.
    Feldman Barrett, Lisa
    et al.
    Northeastern University, MA 02115 USA; Massachusetts Gen Hospital, MA 02129 USA; Harvard Medical Sch, MA 02129 USA; Massachusetts Gen Hospital, MA 02114 USA; Harvard Medical Sch, MA 02115 USA.
    Quigley, Karen S.
    Northeastern University, MA 02115 USA.
    Hamilton, Paul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    An active inference theory of allostasis and interoception in depression2016In: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 371, no 1708, article id 20160011Article in journal (Refereed)
    Abstract [en]

    In this paper, we integrate recent theoretical and empirical developments in predictive coding and active inference accounts of interoception (including the Embodied Predictive Interoception Coding model) with working hypotheses from the theory of constructed emotion to propose a biologically plausible unified theory of the mind that places metabolism and energy regulation (i.e. allostasis), as well as the sensory consequences of that regulation (i.e. interoception), at its core. We then consider the implications of this approach for understanding depression. We speculate that depression is a disorder of allostasis, whose myriad symptoms result from a locked in brain that is relatively insensitive to its sensory context. We conclude with a brief discussion of the ways our approach might reveal new insights for the treatment of depression. This article is part of the themed issue Interoception beyond homeostasis: affect, cognition and mental health.

  • 15.
    Frost Bellgowan, Julie
    et al.
    Laureate Institute Brain Research, OK USA.
    Molfese, Peter
    Haskins Labs Inc, CT USA.
    Marx, Michael
    Stanford University, CA 94305 USA.
    Thomason, Moriah
    Wayne State University, MI USA.
    Glen, Daniel
    NIMH, MD 20892 USA.
    Santiago, Jessica
    Laureate Institute Brain Research, OK USA.
    Gotlib, Ian H.
    Stanford University, CA 94305 USA.
    Drevets, Wayne C.
    Laureate Institute Brain Research, OK USA; Janssen Pharmaceut, Belgium.
    Hamilton, Paul J.
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Laureate Institute Brain Research, OK USA.
    A Neural Substrate for Behavioral Inhibition in the Risk for Major Depressive Disorder2015In: Journal of the American Academy of Child and Adolescent Psychiatry, ISSN 0890-8567, E-ISSN 1527-5418, Vol. 54, no 10, p. 841-848Article in journal (Refereed)
    Abstract [en]

    Objective: Behavioral inhibition (BI) is an early developing trait associated with cautiousness and development of clinical depression and anxiety. Little is known about the neural basis of BI and its predictive importance concerning risk for internalizing disorders. We looked at functional connectivity of the default-mode network (DMN) and salience network (SN), given their respective roles in self-relational and threat processing, in the risk for internalizing disorders, with an emphasis on determining the functional significance of these networks for BI. Method: We used functional magnetic resonance imaging to scan, during the resting state, children and adolescents 8 to 17 years of age who were either at high familial risk (HR; n = 16) or low familial risk (LR; n = 18) for developing clinical depression and/or anxiety. Whole-brain DMN and SN functional connectivity were estimated for each participant and compared across groups. We also compared the LR and HR groups on levels of BI and anxiety, and incorporated these data into follow-up neurobehavioral correlation analyses. Results: The HR group, relative to the LR group, showed significantly decreased DMN connectivity with the ventral striatum and bilateral sensorimotor cortices. Within the HR group, trait BI increased as DMN connectivity with the ventral striatum and sensorimotor cortex decreased. The HR and LR groups did not differ with respect to SN connectivity. Conclusion: Our findings show, in the risk for internalizing disorders, a negative functional relation between brain regions supporting self-relational processes and reward prediction. These findings represent a potential neural substrate for behavioral inhibition in the risk for clinical depression and anxiety.

  • 16.
    Gowin, Joshua L.
    et al.
    NIAAA, MD USA.
    Vatsalya, Vatsalya
    NIAAA, MD USA; University of Louisville, KY 40292 USA; Robley Rex VAMC, KY USA.
    Westman, Jonathan G.
    NIAAA, MD USA.
    Schwandt, Melanie L.
    NIAAA, MD 20892 USA.
    Bartlett, Selena
    Queensland University of Technology, Australia.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Momenan, Reza
    NIAAA, MD USA.
    Ramchandani, Vijay A.
    NIAAA, MD USA.
    The Effect of Varenicline on the Neural Processing of Fearful Faces and the Subjective Effects of Alcohol in Heavy Drinkers2016In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 40, no 5, p. 979-987Article in journal (Refereed)
    Abstract [en]

    Background: Pharmacotherapies for alcohol use disorder have been shown to reduce hazardous drinking and improve overall health. The effect sizes for the effectiveness of these medications, however, are small, underscoring the need to expand the range of therapeutics and develop personalized treatment approaches. Recent studies have suggested that varenicline, an 42-nicotinic partial agonist widely used for smoking cessation, can help alcoholics reduce drinking, but the neurocognitive underpinnings of its effectiveness remain largely unexplored. Methods: In this double-blind study, 32 heavy drinkers were randomized to receive varenicline (2 mg/d) or placebo. After 2 weeks of dosing, participants underwent functional MRI scans, during which they viewed images of faces with either neutral or fearful expressions at baseline and following an intravenous alcohol infusion to a target breath alcohol concentration of 80 mg%. Blood oxygen level-dependent (BOLD) response was analyzed with Analysis of Functional Neuroimaging software. Linear mixed-effects models were used to examine the effects of facial expression (fearful vs. neutral) and medication (placebo vs. varenicline) on BOLD response. The effect of medication on measures of subjective response to alcohol was also examined. Results: Results indicated a significant facial expression-by-medication interaction in the left amygdala. The groups showed equivalent activation to neutral faces, but, whereas the placebo group showed increased activation to fearful faces, the varenicline group showed no change in activation. Amygdala activation to fearful faces correlated with number of drinks in the previous 90 days and Obsessive Compulsive Drinking Scale scores. There was no effect of varenicline on subjective response to alcohol. Conclusions: Our results indicate that varenicline may disrupt amygdala response to fearful faces in heavy drinkers. Further, amygdala activation correlated with alcohol consumption, suggesting that the effects of varenicline may be related to aspects of drinking behavior. These results suggest that amygdala response to fearful faces may be developed as a biomarker of the effectiveness of medications being developed for the treatment of alcohol use disorder.

  • 17.
    Gustafsson, Berit M.
    et al.
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Högland Hospital, Sweden; Jönköping University, Sweden.
    Gustafsson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. 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, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Hospital Jönköping, Sweden.
    The Strengths and Difficulties Questionnaire (SDQ) for preschool childrena Swedish validation2016In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 70, no 8, p. 567-574Article in journal (Refereed)
    Abstract [en]

    Background: In Sweden, 80-90% of children aged 1-5 years attend preschool, and that environment is well suited to identify behaviours that may be signs of mental health problems. The Strengths and Difficulties Questionnaire (SDQ) is a well-known short and structured instrument measuring child behaviours that indicate mental health problems well suited for preschool use.Aim: To investigate whether SDQ is a reliable and valid instrument for identifying behavioural problems in children aged 1-3 years and 4-5 years in a Swedish population, as rated by preschool teachers.Methods: Preschools situated in different sized municipalities in Sweden participated. The preschool teacher rated each individual child. Concurrent validity was tested using the Child-Teacher Report Form (C-TRF) and Child Engagement Questionnaire (CEQ). Exploratory factor analysis was conducted for age groups, 1-3 years and 4-5 years.Results: The preschool teachers considered most of the SDQ items relevant and possible to rate. For the children aged 1-3 years, the subscales Hyperactivity (Cronbach alpha=0.84, split half=0.73) and Conduct (Cronbach alpha=0.76, split half=0.80) were considered to be valid. For the age group 4-5 years, the whole original SDQ scale, 4-factor solution was used and showed reasonable validity (Cronbach alpha=0.83, split half=0.87).Conclusion: SDQ can be used in a preschool setting by preschool teachers as a valid instrument for identifying externalizing behavioural problems (hyperactivity and conduct problems) in young children.Clinical implications: SDQ could be used to identify preschool children at high-risk for mental health problems later in life.

  • 18.
    Hamilton, Paul J.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Glover, Gary H.
    Stanford University, CA, USA.
    Bagarinao, Epifanio
    Stanford University, CA, USA.
    Chang, Catie
    National Institutes of Health, Bethesda, MD, USA.
    Mackey, Sean
    Stanford University, CA, USA.
    Sacchet, Matthew D.
    Stanford University, CA, USA.
    Gotlib, Ian H.
    Stanford University, CA, USA.
    Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder2016In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 249, p. 91-96Article in journal (Refereed)
    Abstract [en]

    Neural models of major depressive disorder (MDD) posit that over-response of components of the brains salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the realneurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 19.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Substansrelaterade och addiktiva störningar2016In: Psykiatri / [ed] Jörgen Herlofson, Lund: Studentlitteratur, 2016, 2, p. 493-536Chapter in book (Other academic)
    Abstract [en]

    Användning av psykoaktiva substanser (eller "droger") leder till omfattande folkhälsoproblem, men är inte lätt att få in i enkla diagnoskategorier. Det är omdebatterat hurvida substansbruk ska ses som en "sjukdom" och vara en angelägenhet för sjukvården. Vi ska emellertid se att substansbruk ofta uppvisar grundläggande likheter med andra kroniska sjukdomar.

  • 20.
    Heilig, Markus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Carlezon, William A.
    Harvard University, MA USA.
    Editorial Material: Circumspectives: Cannabis and Psychiatric Illness: Blunt Thoughts in NEUROPSYCHOPHARMACOLOGY, vol 41, issue 2, pp 391-3922016In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 41, no 2, p. 391-392Article in journal (Other academic)
    Abstract [en]

    n/a

  • 21.
    Heilig, Markus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Epstein, David H.
    NIDA, MD 21044 USA.
    Nader, Michael A.
    Wake Forest School Med, NC 27157 USA.
    Shaham, Yavin
    NIDA, MD 21044 USA.
    Time to connect: bringing social context into addiction neuroscience2016In: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 17, no 9, p. 592-599Article, review/survey (Refereed)
    Abstract [en]

    Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.

  • 22.
    Hjern, Anders
    et al.
    Stockholm University, Sweden .
    Rajmil, Luis
    Catalan Agency Health Informat Assessment and Qual, Spain .
    Bergstrom, Malin
    Stockholm University, Sweden .
    Berlin, Marie
    National Board Health and Welf, Sweden .
    Gustafsson, Per A.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Modin, Bitte
    Stockholm University, Sweden .
    Migrant density and well-being-A national school survey of 15-year-olds in Sweden2013In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 23, no 5, p. 823-828Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to investigate the impact of migrant density in school on the well-being of pupils with a migrant origin in first as well as second generation. Methods: Cross-sectional analysis of data from a national classroom survey of 15-year-old Swedish schoolchildren. The study population included 76 229 pupils (86.5% participation) with complete data set from 1352 schools. Six dimensions of well-being from the KIDSCREEN were analysed in two-level linear regression models to assess the influence of migrant origin at individual level and percentage of students with a migrant origin at school level, as well as interaction terms between them. Z-scores were used to equalize scales. Results: A high density (andgt; 50%) of pupils with a migrant origin in first or second generation was associated with positive well-being on all six scales for foreign-born pupils originating in Africa or Asia compared with schools with low (andlt; 10%) migrant density. The effect sizes were 0.56 for boys and 0.29 for girls on the comprehensive KIDSCREEN 10-index (P andlt; 0.001) and 0.61 and 0.34, respectively, for psychological well-being (P andlt; 0.001). Of the boys and girls born in Africa or Asia, 31.6% and 34.6%, respectively, reported being bullied during the past week in schools with low (andlt; 10%) migrant density. Conclusions: Pupils born in Africa or Asia are at high risk for being bullied and having impaired well-being in schools with few other migrant children. School interventions to improve peer relations and prevent bullying are needed to promote well-being in non-European migrant children.

  • 23.
    Karlsson, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Aziz, Abdul Maruf Asif
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rehman, Faazal
    NIAAA, MD USA.
    Pitcairn, Caleb
    Laboratory of Clinical and Translational Studies, NIAAA, NIH, Bethesda, Maryland, USA.
    Barchiesi, Riccardo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Barbier, Estelle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Wendel Hansen, Mikaela
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gehlert, Don
    CNS Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
    Steensland, Pia
    Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Melanin-Concentrating Hormone and Its MCH-1 Receptor: Relationship Between Effects on Alcohol and Caloric Intake2016In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 40, no 10, p. 2199-2207Article in journal (Refereed)
    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.

  • 24.
    Karlsson, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rehman, Faazal
    NIAAA, MD USA.
    Damadzic, Ruslan
    NIAAA, MD USA.
    Atkins, Alison Lynn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Schank, Jesse R.
    University of Georgia, GA 30602 USA.
    Gehlert, Donald R.
    Lilly Research Labs, IN USA.
    Steensland, Pia
    Karolinska Institute, Sweden.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Correction: The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation (vol 233, nr 12, pp. 2355–2363, 2016)2016In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 21-22, p. 3825-3825Article in journal (Other academic)
    Abstract [en]

    n/a

  • 25.
    Karlsson, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rehman, Faazal
    NIH, MD 20892 USA.
    Damdazic, Ruslan
    NIH, MD 20892 USA.
    Atkins, Alison Lynn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Schank, Jesse R.
    University of Georgia, GA 30602 USA.
    Gehlert, Donald R.
    Eli Lilly and Co, IN 46285 USA.
    Steensland, Pia
    Karolinska Institute, Sweden.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation2016In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 12, p. 2355-2363Article in journal (Refereed)
    Abstract [en]

    Melanin-concentrating hormone (MCH) is involved in the regulation of food intake and has recently been associated with alcohol-related behaviors. Blockade of MCH-1 receptors (MCH1-Rs) attenuates operant alcohol self-administration and decreases cue-induced reinstatement, but the mechanism through which the MCH1-R influences these behaviors remains unknown. MCH1-Rs are highly expressed in the nucleus accumbens shell (NAcSh) where they are co-expressed with dopamine (DA) receptors. MCH has been shown to potentiate responses to dopamine and to increase phosphorylation of DARPP-32, an intracellular marker of DA receptor activation, in the NAcSh. In the present study, we investigated the role of the MCH1-R in alcohol reward using the conditioned place preference (CPP) paradigm. We then used immunohistochemistry (IHC) to assess activation of downstream signaling after administration of a rewarding dose of alcohol. We found that alcohol-induced CPP was markedly decreased in mice with a genetic deletion of the MCH1-R as well as after pharmacological treatment with an MCH1-R antagonist, GW803430. In contrast, an isocaloric dose of dextrose did not produce CPP. The increase in DARPP-32 phosphorylation seen in wildtype (WT) mice after acute alcohol administration in the NAcSh was markedly reduced in MCH1-R knock-out (KO) mice. Our results suggest that MCH1-Rs regulate the rewarding properties of alcohol through interactions with signaling cascades downstream of DA receptors in the NAcSh.

  • 26.
    Karlstrand, Lisbet
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Sonesson, Katharina
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Barnets röst på nätverksmöten. Hur framförs den?2016Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The present qualitative study showed descriptions from professionals, how the voice of the child was carried forward during network meetings. The study also described what is influencing and who is judging the child’s participation in a network meeting. Ten therapists at the child- and youth psychiatry department in south-east Sweden were interviewed by means of a semi-structured question guide.

    One conclusion is that network meetings almost always may be adapted in a way that the child is able to attend. Hence, the result does not only include descriptions of methods and techniques which may assist in listening to the child, but also reflections around the structure of the meeting, in order to, on the whole enabling a child focus. In the investigation an emotional climate appeared to be important in order for the voice of the child to be carried forward and to be understood. Another conclusion was that the child should not attend in all meetings. There appeared some uncertainty about who has the ultimate responsibility in the judgement of the participation of the child.

  • 27.
    Mayo, Leah M.
    et al.
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. University of Chicago, IL, USA.
    de Wit, Harriet
    University of Chicago, IL, USA.
    Acquisition of Conditioned Responses to a Novel Alcohol-Paired Cue in Social Drinkers2016In: Journal of Studies on Alcohol and Drugs, ISSN 1937-1888, E-ISSN 1938-4114, Vol. 77, no 2, p. 317-326Article in journal (Refereed)
    Abstract [en]

    Objective: This study examined the acquisition of conditioning between novel stimuli and single doses of alcohol in social drinkers. Environmental stimuli present during the consumption of alcohol or other drugs come to elicit conditioned responses that subsequently increase drug seeking. However, relatively few studies have examined the process of acquisition of these conditioned drug responses in human subjects. Method: We used a procedure previously developed to study acquisition of conditioned responses to a methamphetamine-associated cue. In the present study we applied the paradigm to alcohol, pairing de novo neutral cues with alcohol in social drinkers (N=36). We obtained measures of self-report, behavioral preference, emotional reactivity (assessed using facial electromyography), and attention to specific cues paired with administration of 0.6 g/kg 95% absolute alcohol or placebo. Results: After conditioning, participants showed an increase in attention toward the alcohol-paired cue, and this increase was associated with ratings of liking the alcohol-containing beverage during the conditioning sessions. In contrast to our previous findings with methamphetamine, the alcohol-paired cue did not elicit changes in emotional reactivity (measured by facial electromyography) or behavioral preference. Conclusions: This study extends our previous findings with a stimulant drug to. alcohol and highlights possible similarities and differences in conditioning with different classes of drugs. Conditioning with alcohol was less robust than with methamphetamine, but in both cases the conditioning that did occur was related to positive subjective drug response.

  • 28.
    Nordlander, Monica
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Åhlander, Camilla
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Effekter av föräldrautbildningen STRATEGI på föräldrars syn på familjens funktion2016Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The study, a multicenter study, conducted at the child psychiatric clinics in central Sweden, with a quantitative approach and consecutively selection aimed to explore whether a participation in the parental training programme STRATEGI for caregivers to children with ADHD affects the perception of family function. It meant also to examine whether self-rating scale SCORE-15 can distinguish a clinical population in Sweden and be validated using the instrument Familjeklimat. Data collection was done through repeated measurements using standardized protocols in connection as the caregivers participated in the programme. The results showed that participation in the parental education programme STRATEGI could have an effect on the perception of family function for the caregivers who reported having the largest impact of problems. The results of the study correlates well with measurements from previous studies of clinical populations (O'Hanrahan (2016). The validity of the SCORE-15 appear to be high. SCORE-15 seems adapted to a Swedish population and is expected to distinguish a clinical population. SCORE-15 is therefore a useful clinical instrument.

  • 29.
    Rundgren, Sara
    et al.
    Orebro Univ, Sweden.
    Brus, Ole
    Orebro Univ, Sweden.
    Bave, Ullvi
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Landen, Mikael
    Karolinska Inst, Sweden; Gothenburg Univ, Sweden.
    Lundberg, Johan
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Nordanskog, Pia
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Nordenskjold, Axel
    Orebro Univ, Sweden.
    Improvement of postpartum depression and psychosis after electroconvulsive therapy: A population-based study with a matched comparison group2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 235, p. 258-264Article in journal (Refereed)
    Abstract [en]

    Introduction: Electroconvulsive therapy (ECT) is used to treat postpartum depression and psychosis based on clinical experience and small observational studies. Aims: The primary aim was to test the hypothesis that the response rate to ECT for depression and psychosis is higher during the postpartum period than outside this period. The secondary aim was to identify predictors of a response to ECT during the postpartum period. Materials and methods: Cases with postpartum depression and/or psychosis received ECT within 6 months of delivery. A matched comparison group with depression and/or psychosis (not within the postpartum period) was identified from the Swedish National Quality Register for ECT. The improvement 1 week after ECT was classified according to the Clinical Global Impressions Scale - Improvement scale (CGI-I) as responder (CGI-I score 1-2) or non-responder (CGI-I score 3-7). Results: 185 cases and 185 comparison group subjects were included (46% with psychosis in each groups). More cases (87.0%) than comparison group subjects (73.5%) responded to ECT (p = 0.001). Adjusted binary regression analysis revealed that more severe symptoms prior to treatment were the only statistically significant predictor of response. Limitations: There was no control group without ECT treatment. Conclusion: The response rate of those with postpartum depression and/or psychosis to ECT was high. The response rate of patients with psychosis or depression was higher during the postpartum period than outside it. This study supports the use of ECT for severe forms of postpartum depression and/or psychosis.

  • 30.
    Sailer, Uta
    et al.
    University of Gothenburg, Sweden; University of Oslo, Norway.
    Triscoli, Chantal
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Haggblad, Gisela
    Gothenburg University, Sweden.
    Hamilton, Paul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Sahlgrens University Hospital, Sweden.
    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.
    Temporal dynamics of brain activation during 40 minutes of pleasant touch2016In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 139, p. 360-367Article in journal (Refereed)
    Abstract [en]

    Introduction: Touch is important for individuals subjective well-being, is typically rewarding, and is one of few sensory stimuli which are experienced as pleasant for a rather long time. This study tracked brain activation during slow stroking stimulation of the arm that was applied continuously for 40 min - a much longer time than what previous studies have investigated. Methods: 25 subjects were stroked for 40 min with a soft brush while they were scanned with functional Magnetic Resonance Imaging, and rated the perceived pleasantness of the brush stroking. Two resting baselines were included. Whole brain-based analyses investigated the neural response to long-lasting stroking. Results: Stroking was perceived as pleasant throughout scanning and activated areas that were previously found to be involved in the processing of pleasant touch. Activation in primary somatosensory cortex (S1) and S2, subdivision OP1, decreased over time, whereas activation in orbito-frontal gyrus (OFC) and putamen strongly increased until reaching a plateau after approximately 20 min. Similarly, functional connectivity of posterior insula with middle cingulate and striatal regions increased over time. Discussion: Long-lasting stroking was processed in similar areas as shorter-lasting stroking. The decreased activation in somatosensory cortices over time may represent stimulus habituation, whereas increased activation in OFC and putamen may relate to the stimulations subjective reward value. This involvement of reward-related brain circuits can facilitate maintenance of long-lasting social touch interactions. (C) 2016 The Authors. Published by Elsevier Inc.

  • 31.
    Schwandt, Melanie L.
    et al.
    NIAAA, MD USA.
    Cortes, Carlos R.
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. NIAAA, MD USA.
    Kwako, Laura E.
    NIAAA, MD USA.
    George, David T.
    NIAAA, MD USA.
    Momenan, Reza
    NIAAA, MD USA.
    Sinha, Rajita
    Yale University, CT 06520 USA.
    Grigoriadis, Dimitri E.
    Neurocrine Bioscience, CA USA.
    Merlo Pich, Emilio
    Imperial Coll London, England.
    Leggio, Lorenzo
    NIAAA, MD USA; NIDA, MD 20892 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. NIAAA, MD USA.
    The CRFI Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects2016In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 41, no 12, p. 2818-2829Article in journal (Refereed)
    Abstract [en]

    Blockade of corticotropin-releasing factor receptor I (CRFI) suppresses stress-induced alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRFI antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced alcohol craving in alcohol-dependent patients. Anxious, alcohol-dependent women (age 21-65 years, n = 39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test Craving was evaluated using two established protocols, one that combines a social stressor with physical alcohol cue exposure, and one that uses guided imagery to present personalized stress, alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and alcohol cues. In contrast to our recent observations with another CRFI antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left alcohol craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRFI antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRFI blockade in stress-induced alcohol craving and relapse.

  • 32.
    Selberg, Malin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Självskadebeteende och Expressed Emotion. En uppföljning av IKB-Intensiv Kontextuell Behandling.2016Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Abstract

    To intentionally cut, burn or hurt oneself severely is associated with great suffering and often arouse strong reactions within the family context. The problem is extensive and self-harm appears to be a strong predictor of suicide attempts and completed suicides. Globally, suicide is the second leading cause of death among young people. Effective treatment models for this group is urgent. In Sweden, (Uppsala) the model IKB - Intensive Contextual Treatment was developed for adolescents with self-harm and / or suicidal behavior, and their families in order to provide support. IKB is an integrated individual and family therapeutic model. The aim of the study were to evaluate the effectiveness of IKB in relation to frequency of self-harm and levels of Expressed emotion. A total of 34 families participated in the study and they all received treatment in the context of the IKB-model. The families completed the self-assessment forms for data collection before treatment, after treatment and follow-up. Results showed efficiency to reduce self-harm among adolescents and to decrease levels of Expressed emotion. The outcome of the study are discussed based on previous research and methodological issues.

  • 33.
    Sells, Joanna R.
    et al.
    NIAAA, MD 20892 USA; Uniformed Serv University of Health Science, MD 20814 USA.
    Waters, Andrew J.
    Uniformed Serv University of Health Science, MD 20814 USA.
    Schwandt, Melanie L.
    NIAAA, MD 20814 USA.
    Kwako, Laura E.
    NIAAA, MD 20814 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    George, David T.
    NIAAA, MD 20814 USA.
    Ramchandani, Vijay A.
    NIAAA, MD 20892 USA.
    Characterization of comorbid PTSD in treatment-seeking alcohol dependent inpatients: Severity and personality trait differences2016In: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 163, p. 242-246Article in journal (Refereed)
    Abstract [en]

    Background: Post-traumatic stress disorder (PTSD) is often comorbid with alcohol dependence (AD), but little is known about the characteristics of AD treatment-seeking inpatients with PTSD. We examined differences between treatment-seeking alcohol dependent inpatients with and without comorbid PTSD. We hypothesized that those with AD and PTSD would have higher levels of: (1) alcohol use and AD severity; (2) anxiety and mood disorders; (3) neuroticism. Methods: Individuals (N = 411, mean age = 41.7 +/- 10.0 years) with AD were monitored over 30 days in a suburban inpatient alcohol treatment setting. Patients were evaluated to identify AD and comorbid PTSD, mood and anxiety disorders, alcohol use and dependence severity, personality, and aggression. Results: Those with PTSD (19% of the sample) did not differ in the amount of alcohol consumed, but had greater: (1) severity of AD (p = 0.001, d = 0.44); (2) diagnosis of anxiety (p = 0.000, OR = 3.64) and mood (p = 0.000, OR = 4.83) disorders; and (3) levels of neuroticism (p amp;lt; 0.001, d = 0.67) and aggression (p amp;lt; 0.001, d = 0.81). Conclusions: AD patients with comorbid PTSD present a more severe phenotype across AD severity, frequency of anxiety and mood disorders, and levels of neuroticism and aggression. This group may benefit from concurrent treatment of both AD and PTSD. Future research can investigate neuroticism as a potential treatment target. Published by Elsevier Ireland Ltd.

  • 34.
    Sikora, Magdalena
    et al.
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Tokarski, Krzysztof
    Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland..
    Bobula, Bartosz
    Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland..
    Zajdel, Joanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jastrzębska, Kamila
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Cieślak, Przemysław Eligiusz
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Zygmunt, Magdalena
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Sowa, Joanna
    Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland..
    Smutek, Magdalena
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Kamińska, Katarzyna
    Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Gołembiowska, Krystyna
    Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    Engblom, David
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Hess, Grzegorz
    Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland..
    Przewlocki, Ryszard
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland; Department of Neurobiology and Neuropsychology, Institute of Applied Psychology, Jagiellonian University, 30-348 Krakow, Poland.
    Rodriguez Parkitna, Jan
    Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
    NMDA Receptors on Dopaminoceptive Neurons Are Essential for Drug-Induced Conditioned Place Preference.2016In: eNeuro, ISSN 2373-2822, Vol. 3, no 3, article id ENEURO.0084-15.2016Article in journal (Refereed)
    Abstract [en]

    Plasticity of the brain's dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1(D1CreERT2) mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1(D1CreERT2) mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general.

  • 35.
    Spagnolo, Primavera A.
    et al.
    NIAAA, MD USA.
    Ramchandani, Vijay A.
    NIAAA, MD USA.
    Schwandt, Melanie L.
    NIAAA, MD USA.
    Kwako, Laura E.
    NIAAA, MD USA.
    George, David T.
    NIAAA, MD USA.
    Mayo, Leah
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Hillard, Cecilia J.
    Medical Coll Wisconsin, WI 53226 USA; Medical Coll Wisconsin, WI 53226 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence2016In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 40, no 11, p. 2426-2434Article in journal (Refereed)
    Abstract [en]

    BackgroundA common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses. MethodsForty-nine patients with PTSD and AD were admitted for 4weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity. ResultsFAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2-arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain. ConclusionsThis is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics.

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