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  • 1. Agnafors, S.
    et al.
    Sydsjö, G.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Bladh, M.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Svedin, C.
    Behaviour problems in children-a longitudinal study of genetic and environmental factors2015In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 24, p. S35-S35Article in journal (Other academic)
  • 2.
    Agnafors, Sara
    et al.
    Linkoping Univ, Fac Hlth Sci, IKE, Div Child & Adolescent Psychiat, S-58185 Linkoping, Sweden.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Bladh, Marie
    Linkoping Univ, Div Obstet & Gynecol IKE, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Sydsjö, Gunilla
    Linkoping Univ, Div Obstet & Gynecol IKE, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Dekeyser, Linda
    Linkoping Univ, Div Obstet & Gynecol IKE, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Svedin, Carl-Göran
    Linkoping Univ, Fac Hlth Sci, IKE, Div Child & Adolescent Psychiat, S-58185 Linkoping, Sweden.
    Effect of gene, environment and maternal depressive symptoms on pre-adolescence behavior problems: a longitudinal study2013In: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 7, article id 10Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Depression is a common and disabling condition with a high relapse frequency. Maternal mental health problems and experience of traumatic life events are known to increase the risk of behavior problems in children. Recently, genetic factors, in particular gene-by-environment interaction models, have been implicated to explain depressive etiology. However, results are inconclusive.

    METHODS:

    Study participants were members of the SESBiC-study. A total of 889 mothers and their children were followed during the child's age of 3 months to 12 years. Information on maternal depressive symptoms was gathered postpartum and at a 12 year follow-up. Mothers reported on child behavior and traumatic life events experienced by the child at age 12. Saliva samples were obtained from children for analysis of 5-HTTLPR and BDNF Val66Met polymorphisms.

    RESULTS:

    Multivariate analysis showed a significant association between maternal symptoms of depression and anxiety, and internalizing problems in 12-year-old children (OR 5.72, 95% CI 3.30-9.91). Furthermore, carriers of two short alleles (s/s) of the 5-HTTLPR showed a more than 4-fold increased risk of internalizing problems at age 12 compared to l/l carriers (OR 4.73, 95% CI 2.14-10.48). No gene-by-environment interaction was found and neither depressive symptoms postpartum or traumatic experiences during childhood stayed significant in the final model.

    CONCLUSIONS:

    Concurrent maternal symptoms of depression and anxiety are significant risk factors for behavior problems in children, which need to be taken into account in clinical practice. Furthermore, we found a main effect of 5-HTTLPR on internalizing symptoms in 12-year-old children, a finding that needs to be confirmed in future studies.

  • 3. Agnafors, Sara
    et al.
    Svedin, Carl Göran
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Bladh, Marie
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Sydsjö, Gunilla
    A Biopsychosocial Approach to Risk and Resilience on Behavior in Children Followed from Birth to Age 122017In: Child Psychiatry and Human Development, ISSN 0009-398X, E-ISSN 1573-3327, Vol. 48, no 4, p. 584-596Article in journal (Refereed)
    Abstract [en]

    An increasing prevalence of mental health problems calls for more knowledge into factors associated with resilience. The present study used multiple statistical methodologies to examine a biopsychosocial model of risk and resilience on preadolescence behavior. Data from 889 children and mothers from a birth cohort were used. An adversity score was created by combining maternal symptoms of depression, psychosocial risk and children's experiences of life events. The proposed resilience factors investigated were candidate genetic polymorphisms, child temperament, social functioning, and maternal sense of coherence. The l/l genotype of the serotonin transporter linked polymorphic region was associated with lower internalizing scores, but not mainly related to the level of adversity. An easy temperament was associated with resilience for children exposed to high adversity. Social functioning was found to be promotive independent of the risk level. The results support a multiple-level model of resilience indicating effects, though small, of both biological and psychosocial factors.

  • 4.
    Agnafors, Sara
    et al.
    Linkoping Univ, Dept Clin & Expt Med, Fac Hlth Sci, Div Child & Adolescent Psychiat, SE-58185 Linkoping, Sweden..
    Sydsjö, Gunilla
    Linkoping Univ, Div Obstet & Gynaecol, Dept Clin & Expt Med, Fac Hlth Sci, SE-58185 Linkoping, Sweden..
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Bladh, Marie
    Linkoping Univ, Div Obstet & Gynaecol, Dept Clin & Expt Med, Fac Hlth Sci, SE-58185 Linkoping, Sweden..
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Svedin, Carl Göran
    Linkoping Univ, Dept Clin & Expt Med, Fac Hlth Sci, Div Child & Adolescent Psychiat, SE-58185 Linkoping, Sweden..
    Early predictors of behavioural problems in pre-schoolers: a longitudinal study of constitutional and environmental main and interaction effects2016In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 16, article id 76Article in journal (Refereed)
    Abstract [en]

    Background: The early environment is important for child development and wellbeing. Gene-by-environment studies investigating the impact of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the Brain Derived Neurotrophic Factor (BDNF) Val66Met polymorphisms by life events on mental health and behaviour problems have been inconclusive. Methodological differences regarding sample sizes, study population, definitions of adversities and measures of mental health problems obstacle their comparability. Furthermore, very few studies included children. The aim of this study was to examine the associations between a broad range of risk factors covering pregnancy and birth, genetic polymorphism, experience of multiple life events and psychosocial environment, and child behaviour at age 3, using a comparably large, representative, population-based sample. Methods: A total of 1,106 children, and their mothers, were followed from pregnancy to age 3. Information on pregnancy and birth-related factors was retrieved from the Medical Birth Register. Questionnaires on depressive symptoms, child behaviour and child experiences of life events were filled in by the mothers. Child saliva samples were used for genotyping the 5-HTTLPR and BDNF Val66Met polymorphisms. Multiple logistic regression was used to investigate the association between psychological scales and genetic polymorphisms. Results: Symptoms of postpartum depression increased the risk of both internalizing and externalizing problems. Experience of multiple life events was also a predictor of behavioural problems across the scales. No gene-by-environment or gene-by-gene-by-environment interactions were found. Children of immigrants had an increased risk of internalizing problems and parental unemployment was significantly associated with both internalizing and externalizing type of problems. Conclusion: This study shows the importance of the psychosocial environment for psychosocial health in preschool children, and adds to the literature of null-findings of gene-by-environment effects of 5-HTTLPR and BDNF in children.

  • 5.
    Aniruddha, Todkar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hodgins, Sheilagh
    Nilsson W., Kent
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Effect of early life stress and ethanol consumption on Pomc and Avp expression in rat hypothalamus2014In: Alcohol, ISSN 0741-8329, E-ISSN 1873-6823, Vol. 48, no 2, p. 193-193Article in journal (Other academic)
  • 6.
    Bendre, Megha
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Checknita, Dave
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Tiihonen, Jari
    Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden..
    Hodgins, Sheilagh
    Univ Montreal, Inst Univ Sante Mentale Montreal, Montreal, PQ, Canada..
    Nillson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Associations Between MAOA-uVNTR Genotype, Maltreatment, MAOA Methylation, and Alcohol Consumption in Young Adult Males2018In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 42, no 3, p. 508-519Article in journal (Refereed)
    Abstract [en]

    Background

    Epigenetic mechanisms are candidate moderators of the effect of maltreatment on brain and behavior. Interactions between maltreatment and the monoamine oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) are associated with alcohol-related problems. However, presently it is not known whether DNA methylation moderates this association. The study focused on 53 young adult males and aimed to determine whether MAOA methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment, and whether alcohol consumption moderated the association of MAOA methylation with the interaction of MAOA-uVNTR and maltreatment.

    Methods

    MAOA-uVNTR genotypes with 3 and > 3 repeats were categorized as short (S) and long (L), respectively. Data on maltreatment were obtained retrospectively, using self-reported questionnaires. DNA methylation of 16 candidate CpGs within part of the MAOA first exon and intron was assessed and grouped based on principal component analyses. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C. Moderation effects were assessed and probed using the moderated moderation model and Johnson-Neyman's method, respectively.

    Results

    Carriers of the S allele, who experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in the first intron) MAOA methylation levels, reported higher AUDIT score in contrast to L-allele carriers. Carriers of the S allele, who reported higher AUDIT-C score and experienced maltreatment, displayed lower Component 3 (mean of CpGs 2-6 in the first exon) MAOA methylation levels than L-allele carriers.

    Conclusions

    Intronic methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption moderated the association of exonic methylation with the interaction of MAOA-uVNTR and maltreatment. These results suggest that epigenetic factors as well as genotype and maltreatment play a role in the development of alcohol misuse among young adult males.

  • 7.
    Bendre, Megha
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Early Life Stress and Voluntary Alcohol Consumption in Adulthood Affect Maoa Expression in the Nucleus Accumbens of Outbred Rats2015In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 50Article in journal (Other academic)
  • 8.
    Bendre, Megha
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Kent W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Effect of voluntary alcohol consumption on Maoa expression in the mesocorticolimbic brain of adult male rats previously exposed to prolonged maternal separation.: Maoa,ELS and alcohol2015In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 5, article id e690Article in journal (Refereed)
    Abstract [en]

    Discordant associations between monoamine oxidase A (MAOA) genotype and high alcohol drinking have been reported in human and non-human primates. Environmental influences likely moderate genetic susceptibility. The biological basis for this interplay remains elusive, and inconsistencies call for translational studies in which conditions can be controlled and brain tissue is accessible. The present study investigated whether early life stress and subsequent adult episodic alcohol consumption affect Maoa expression in stress- and reward-related brain regions in the rat. Outbred Wistar rats were exposed to rearing conditions associated with stress (prolonged maternal separation) or no stress during early life, and given free choice between alcohol and/or water in adulthood. Transcript levels of Maoa were assessed in the ventral tegmental area, nucleus accumbens (NAc), medial prefrontal cortex, cingulate cortex, amygdala and dorsal striatum (DS). Blood was collected to assess corticosterone levels. After alcohol consumption, lower blood corticosterone and Maoa expression in the NAc and DS were found in rats exposed to early life stress compared with control rats. An interaction between early life stress and voluntary alcohol intake was found in the NAc. Alcohol intake before death correlated negatively with Maoa expression in DS in high alcohol-drinking rats exposed to early life stress. Maoa expression is sensitive to adulthood voluntary alcohol consumption in the presence of early life stress in outbred rats. These findings add knowledge of the molecular basis of the previously reported associations between early life stress, MAOA and susceptibility to alcohol misuse.

  • 9.
    Bendre, Megha
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nillson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Maoa Methylation: A Molecular Mechanism Behind The Effect Of Early Life Stress And Voluntary Alcohol Consumption On Maoa Expression In Wistar Rats2017In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 52Article in journal (Other academic)
  • 10.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Gulinello, Maria
    Albert Einstein Coll Med, Dept Neurosci, Behav Core Facil, Bronx, NY USA..
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sylven, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sleep duration, depression, and oxytocinergic genotype influence prepulse inhibition of the startle reflex in postpartum women2016In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 26, no 4, p. 767-776Article in journal (Refereed)
    Abstract [en]

    The postpartum period is characterized by a post-withdrawal hormonal status, sleep deprivation, and susceptibility to affective disorders. Postpartum mothering involves automatic and attentional processes to screen out new external as well as internal stimuli. The present study investigated sensorimotor gating in relation to sleep duration, depression, as well as catecholaminergic and oxytocinergic genotypes in postpartum women. Prepulse inhibition (PPI) of the startle reflex and startle reactivity were assessed two months postpartum in 141 healthy and 29 depressed women. The catechol-O-methyltransferase (COMT) Val158Met, and oxytocin receptor (OXTR) rs237885 and rs53576 polymorphisms were genotyped, and data on sleep duration were collected. Short sleep duration (less than four hours in the preceding night) and postpartum depression were independently associated with lower PPI. Also, women with postpartum depression had higher startle reactivity in comparison with controls. The OXTR rs237885 genotype was related to PPI in an allele dose-dependent mode, with T/T healthy postpartum women carriers displaying the lowest PPI. Reduced sensorimotor gating was associated with sleep deprivation and depressive symptoms during the postpartum period. Individual neurophysiological vulnerability might be mediated by oxytocinergic genotype which relates to bonding and stress response. These findings implicate the putative relevance of lower PPI of the startle response as an objective physiological correlate of liability to postpartum depression.

  • 11.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hahn, Andreas
    Ganger, Sebastian
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bannbers, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Epperson, C Neill
    Lanzenberger, Rupert
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Emotional fronto-cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder2014In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 35, no 9, p. 4450-4458Article in journal (Refereed)
    Abstract [en]

    Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings. Hum Brain Mapp, 2014. 

  • 12.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hallberg, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Helander, Anders
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Sundelin Wahlsten, Viveka
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Alcohol Consumption Among Pregnant Women in a Swedish Sample and Its Effects on the Newborn Outcomes2012In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 36, no 10, p. 1779-1786Article in journal (Refereed)
    Abstract [en]

    Background Little is known about the effects of low levels of maternal alcohol intake on the neuropsychological development of the child. This study is part of an ongoing investigation on maternal drinking and presents data on demographic variables, maternal alcohol use, and birth outcomes from that study. Methods The sample comprised 2,264 women from a Swedish antenatal clinic. Retrospective self-report data were collected on alcohol consumption before and during pregnancy, using the Alcohol Use Disorders Identification Test (AUDIT), and on nicotine use. Specific alcohol biomarkers for excessive drinking, carbohydrate-deficient transferrin (CDT) in serum and phosphatidylethanol (PEth) in whole blood, were determined during mid-pregnancy in a subsample of the women. Data on labor and early characteristics of the child were also assessed. Results Before pregnancy, 89% of the women regularly consumed alcohol and 49% reported occasional or frequent binge drinking. Nicotine was used by 15% before and by 5% during pregnancy. During pregnancy, 12% continued using alcohol and 5% also admitted binge drinking. However, all alcohol biomarker values were below the reporting limits (CDT = 1.7% disialotransferrin; total PEth < 0.1 mu mol/L). Self-reported drinking during pregnancy was associated with a higher AUDIT score before pregnancy, nicotine use at the time of the first prenatal visit, older age, and previous legal abortions. Conclusions The AUDIT questionnaire and 2 specific alcohol biomarkers were used in routine maternity care to collect information about drinking during pregnancy and thereby to identify children at risk for alcohol-related complications. While the AUDIT results suggested that a significant number of women continued using alcohol during pregnancy, implying a risk for fetal disorders, the biomarkers showed negative test values thus indicating only modest drinking levels.

  • 13.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hallman, Jarmila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Wallen-Mackenzie, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Haplotype-tag single nucleotide polymorphism analysis of the Vesicular Glutamate Transporter (VGLUT) genes in severely alcoholic women2014In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 219, no 2, p. 403-405Article in journal (Refereed)
  • 14.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien D A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Supraphysiological hormonal status, anxiety disorders, and COMT Val/Val genotype are associated with reduced sensorimotor gating in women2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 60, p. 217-23Article in journal (Refereed)
    Abstract [en]

    Pregnancy is a period characterized by a supraphysiological hormonal status, and greater anxiety proneness, which can lead to peripartum affective symptoms with dramatic consequences not only for the woman but also for the child. Clinical psychiatry is heavily hampered by the paucity of objective and biology-based intermediate phenotypes. Prepulse inhibition (PPI) of the startle response, a neurophysiological measure of sensorimotor gating, has been poorly investigated in relation to anxiety and in pregnant women. In the present study, the PPI of healthy non-pregnant women (n=82) and late pregnant women (n=217) was investigated. Age, BMI, depression and anxiety symptoms, tobacco use, and antidepressant medication were considered. We investigated and provided evidence of lower PPI: (i) in healthy pregnant women compared to healthy non-pregnant controls, (ii) in pregnant women with anxiety disorders compared to healthy pregnant women, (iii) in pregnant women with anxiety disorders using SSRI compared to un-medicated pregnant women with anxiety disorders, and (iv) in healthy pregnant women carrying the COMT Val158Met Val/Val genotype compared to Met carriers. Altogether, a reduced sensorimotor gating as an effect of supraphysiological hormonal status, anxiety disorders, SSRIs, and catecholaminergic genotype, implicate the putative relevance of lower PPI as an objective biological correlate of anxiety proneness in pregnant women. These findings call for prospective studies to dissect the multifactorial influences on PPI in relation to mental health of pregnant women.

  • 15.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Influence of catechol-O-methyltransferase Val158Met polymorphism on startle response in the presence of high estradiol levels2013In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 23, no 7, p. 629-635Article in journal (Refereed)
    Abstract [en]

    Introduction: both human and animal studies have shown a somewhat complex COMT-by-sex interaction effect on brain function and dysfunction. A functional variation in the gene coding for the catechol-O-methyltransferase (COMT) enzyme, which metabolizes dopamine and noradrenaline, has been related to executive and emotional functions, and to sex dimorphism. Aim: to investigate if COMT Val158Met genotype influences startle response in pregnant women, given their physiologically elevated estradiol levels. Methods: seventy-three pregnant women were assessed in gestational week 38 for acoustic startle response, measured by electromyography of the blink reflex, during control condition, positive and negative anticipation stimuli, and pleasant and unpleasant image stimuli. A blood sample was taken for measurement of estradiol levels and genetic analysis. Results: the results indicated a COMT Val158Met effect on startle response across all conditions (main effect of genotype, F(2,70=3.58), p=0.033), where Val/Val women displayed higher startle magnitudes than Val/Met carriers (Cohen's d=0.71). No significant difference by genotype was found in affective modulation. The findings also suggested an estrogen dose-dependent effect of COMT Val158Met on startle reflex. Among women with higher pregnancy-induced estradiol levels, Val/Val carriers had markedly higher startle response across conditions than heterozygotes (Cohen's d=1.36; F(4,21=11.07); p=0.003), while this effect was not present in women with estradiol levels under the median concentration. Conclusions: the observed effect of COMT Val158Met by estradiol on overall startle response is likely to be due to a variable noradrenergic transmission depending on COMT activity in a possible interaction with estradiol. 

  • 16.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hellgren, Chorlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Poromaa, Inger Sundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Pregnancy, anxiety symptoms and catecholaminergic genotype are associated with prepulse inhibition of the startle response in women2015In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 25, p. S216-S216Article in journal (Other academic)
  • 17.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hodgins, Sheilagh
    Rehn, Mattias
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Kent W.
    Clinical and experimental evidence of a link between adrenergic genes, early life stress and alcohol-related phenotypes2014In: Alcohol, ISSN 0741-8329, E-ISSN 1873-6823, Vol. 48, no 2, p. 184-184Article in journal (Other academic)
  • 18.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hallman, Jarmila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Wallen-Mackenzie, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Haplotype tag single-nucleotide polymorphism analysis of the vesicular glutamate transporter 2 gene in severe alcoholism among women2012In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, no S2, p. S397-S397Article in journal (Other academic)
  • 19.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Neuroimaging the Menstrual Cycle and Premenstrual Dysphoric Disorder2015In: Current Psychiatry Reports, ISSN 1523-3812, E-ISSN 1535-1645, Vol. 17, no 10, article id 77Article, review/survey (Refereed)
    Abstract [en]

    Knowledge of gonadal hormone-related influences on human brain anatomy, function, and chemistry is scarce. The present review scrutinized organizational and functional neuroimaging correlates of the menstrual cycle and premenstrual dysphoric disorder (PMDD). Supportive evidence of cyclic short-term structural and functional brain plasticity in response to gonadal hormonal modulation is provided. The paucity of studies, sparsity and discordance of findings, and weaknesses in study design at present hinder the drawing of firm conclusions. Ideal study designs should comprise high-resolution multimodal neuroimaging (e.g., MRI, DTI, rsfMRI, fMRI, PET), hormones, genetic, and behavioral longitudinal assessments of healthy women and PMDD patients at critical time points of the menstrual cycle phase (i.e., early follicular phase, late follicular phase, mid-luteal phase) in a counter-balanced setup. Studies integrating large-scale brain network structural, functional, and molecular neuroimaging, as well as treatment data, will deepen the understanding of neural state, disorder, and treatment markers.

  • 20.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Alpha 2a-Adrenoceptor Gene Expression and Early Life Stress-Mediated Propensity to Alcohol Drinking in Outbred Rats2015In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 12, no 7, p. 7154-7171Article in journal (Refereed)
    Abstract [en]

    Stressful events early in life, later high alcohol consumption and vulnerability to alcohol use disorder (AUD) are tightly linked. Norepinephrine is highly involved in the stress response and the alpha 2A-adrenoceptor, which is an important regulator of norepinephrine signalling, is a putative target in pharmacotherapy of AUD. The aim of the present study was to investigate the effects of early-life stress and adult voluntary alcohol drinking on the alpha 2A-adrenoceptor. The relative expression and promoter DNA methylation of the Adra2a gene were measured in the hypothalamus, a key brain region in stress regulation. A well-characterized animal model of early-life stress was used in combination with an episodic voluntary drinking in adulthood. Alcohol drinking rats with a history of early-life stress had lower Adra2a expression than drinking rats not exposed to stress. Alcohol intake and Adra2a gene expression were negatively correlated in high-drinking animals, which were predominantly rats subjected to early-life stress. The results provide support for a link between early-life stress, susceptibility for high alcohol consumption, and low Adra2a expression in the hypothalamus. These findings can increase our understanding of the neurobiological basis for vulnerability to initiate risk alcohol consumption and individual differences in the response to 2A-adrenoceptor agonists.

  • 21.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Gene-set-based expression and DNA methylation in hypothalamus and pituitary of rats exposed to early life stress and ethanol drinking2014In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 24, no Suppl. 2, p. S663-Article in journal (Other academic)
  • 22.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Mujtaba, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    EXPERIMENTAL EVIDENCE OF A LINK BETWEEN THE alpha 2A-ADRENERGIC RECEPTOR GENE, EARLY LIFE STRESS, AND ETHANOL DRINKING2015In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 50Article in journal (Other academic)
  • 23.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Vumma, Ravi
    Linnaeus Univ, Fac Hlth & Life Sci, Dept Chem & Biomed Sci, Kalmar, Sweden..
    Toffoletto, Simone
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Johansson, Jessica
    Orebro Univ, Sch Hlth & Med Sci, Dept Clin Med, SE-70182 Orebro, Sweden..
    Flyckt, Lena
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Lewander, Tommy
    Orebro Univ, Sch Hlth & Med Sci, Dept Clin Med, SE-70182 Orebro, Sweden..
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Stromstad Acad, Stromstad, Sweden..
    Bjerkenstedt, Lars
    Andreou, Dimitrios
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Söderman, Erik
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Terenius, Lars
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Agartz, Ingrid
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Univ Oslo, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, NORMENT,Inst Clin Med, Oslo, Norway.;Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway..
    Jönsson, Erik G.
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Univ Oslo, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, NORMENT,Inst Clin Med, Oslo, Norway..
    Venizelos, Nikolaos
    Orebro Univ, Sch Hlth & Med Sci, Dept Clin Med, SE-70182 Orebro, Sweden..
    Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia2016In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 74, no 2, p. 96-103Article in journal (Refereed)
    Abstract [en]

    Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5 /LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters ( maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.

  • 24.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nilsson, Kent W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression: A replication study2013In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 23, no 10, p. 1300-1306Article in journal (Refereed)
    Abstract [en]

    Both the serotonin transporter linked promoter region (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms have been shown to interact with unfavourable environment in relation to depression symptoms and to depression diagnosis. Several attempts have been made to study a three-way interaction effect of these factors on depression, however with contradictory results. We aimed to test the hypothesis of a three-way interaction effect and to attempt at replication in an independent population-based sample. Family maltreatment, sexual abuse and depression were self-reported by an adolescent population-based cohort (N=1393) from the county of Västmanland, Sweden. DNA was isolated from saliva, and used for genotyping of the 5-HTTLPR and BDNF Val66Met polymorphisms. Neither 5-HTTLPR or BDNF genotypes separately, nor in interaction with each other had any relation to depression, however in an environment adjusted model a two-way interaction and a three-way interaction effect was found. Both 5-HTTLPR and BDNF Val66Met interacted with unfavourable environment in relation to depressive symptoms (Adj R2=0.19). Depressive symptoms and depression were more common among carriers of either the ss/sl+Val/Val or the ll+Met genotypes in the presence of early-life adversities. This three-way effect was more pronounced among girls. The current study, with a virtually similar set-up compared to previous studies, can partially confirm previous findings and their generalizability. The study also shows the importance of genetic plasticity in individuals with different environmental exposure, for different phenotypic expression.

  • 25.
    Gingnell, Malin
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Toffoletto, Simone
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bannbers, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Emotional anticipation after delivery - a longitudinal neuroimaging study of the postpartum period2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 114Article in journal (Refereed)
    Abstract [en]

    Neuroimaging research has begun to unveil the mechanisms behind emotion processing during the postpartum period, which, in turn, may be of relevance for the development of postpartum depression. The present study sought to longitudinally investigate the neural correlates of emotion anticipation during the postpartum period in healthy women. Functional magnetic resonance imaging was employed to measure the blood oxygen level-dependent signal in the brain in response to anticipation of negative emotional stimuli and during processing of images with positive or negative valence. The participating women were scanned twice: the first scan occurred during the first 48 hours after delivery, and the second was performed 4-6 weeks after delivery. The early postpartum period was characterized by higher anterior cingulate cortex reactivity during anticipation of negative emotional stimuli than the late postpartum period. This was accompanied by a negative relationship with insular reactivity during the early postpartum period and a trend towards an increase in insular reactivity in the late postpartum period. Thus, during the first four weeks of the postpartum period, a diminished top-down regulatory feedback on emotion-related areas of the brain was noted. This finding suggests a physiologically important adaptation during the healthy postpartum period.

  • 26.
    Granholm, Linnea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Todkar, Aniruddah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Bergman, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nillson, Kent
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    The expression of opioid genes in non-classical reward areas depends on early life conditions and ethanol intake2017In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1668, p. 36-45Article in journal (Refereed)
    Abstract [en]

    The young brain is highly sensitive to environmental influences that can cause long-term changes in neuronal function, possibly through altered gene expression. The endogenous opioid system continues to mature after birth and because of its involvement in reward, an inadequate maturation of this system could lead to enhanced susceptibility for alcohol use disorder. Recent studies show that the classical reward areas nucleus accumbens and ventral tegmental area are less affected by early life stress whereas endogenous opioids in non-classical areas, e.g. dorsal striatum and amygdala, are highly responsive. The aim was to investigate the interaction between early life conditions and adult voluntary ethanol intake on opioid gene expression. Male Wistar rats were exposed to conventional rearing, 15, or 360min of daily maternal separation (MS) postnatal day 1-21, and randomly assigned to ethanol or water drinking postnatal week 10-16. Rats exposed to early life stress (MS360) had increased opioid receptor gene (Oprm1, Oprd1 and Oprk1) expression in the dorsal striatum. Ethanol drinking was associated with lower striatal Oprd1 and Oprk1 expression solely in rats exposed to early life stress. Furthermore, rats exposed to early life stress had high inherent Pomc expression in the amygdala but low expression after ethanol intake. Thus, adverse events early in life induced changes in opioid gene expression and also influenced the central molecular response to ethanol intake. These long-term consequences of early life stress can contribute to the enhanced risk for excessive ethanol intake and alcohol use disorder seen after exposure to childhood adversity.

  • 27.
    Granholm, Linnea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    The Effects Of Early Environment And Adult Voluntary Drinking On Pomc Gene Expression In Rats2014In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 38, p. 153A-153AArticle in journal (Other academic)
  • 28.
    Hannerfors, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Iliadis, Stavros I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien D. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Treatment with serotonin reuptake inhibitors during pregnancy is associated with elevated corticotropin-releasing hormone levels2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 58, p. 104-113Article in journal (Refereed)
    Abstract [en]

    Treatment with serotonin reuptake inhibitors (SSRI) has been associated with an increased risk of preterm birth, but causality remains unclear. While placental CRH production is correlated with gestational length and preterm birth, it has been difficult to establish if psychological stress or mental health problems are associated with increased CRH levels. This study compared second trimester CRH serum concentrations in pregnant women on SSRI treatment (n=207) with untreated depressed women (n=56) and controls (n=609). A secondary aim was to investigate the combined effect of SSRI treatment and CRH levels on gestational length and risk for preterm birth. Women on SSRI treatment had significantly higher second trimester CRH levels than controls, and untreated depressed women. CRH levels and SSRI treatment were independently associated with shorter gestational length. The combined effect of SSRI treatment and high CRH levels yielded the highest risk estimate for preterm birth. SSRI treatment during pregnancy is associated with increased CRH levels. However, the elevated risk for preterm birth in SSRI users appear not to be mediated by increased placental CRH production, instead CRH appear as an independent risk factor for shorter gestational length and preterm birth.

  • 29. Harro, J.
    et al.
    Kiive, E.
    Laas, K.
    Vaht, M.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Veidebaum, T.
    MAOA VNTR genotype, psychiatric vulnerability and life course in a population-representative longitudinal study2012In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, no S2, p. S360-S360Article in journal (Other academic)
  • 30.
    Harro, Jaanus
    et al.
    Univ Tartu, Estonian Ctr Behav & Hlth Sci, Div Neuropsychopharmacol, Dept Psychol, EE-50411 Tartu, Estonia.;North Estonia Med Ctr, Psychiat Clin, Tallinn, Estonia..
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    The role of MAO in personality and drug use2016In: Progress in Neuro-psychopharmacology and Biological Psychiatry, ISSN 0278-5846, E-ISSN 1878-4216, Vol. 69, p. 101-111Article in journal (Refereed)
    Abstract [en]

    Monoamine oxidases, both MAO-A and MAO-B, have been implicated in personality traits and complex behaviour, including drug use. Findings supporting the involvement of MAO-A and MAO-B in shaping personality and in the development of strategies of making behavioural choices come from a variety of studies that have examined either prevalence of gene variants in clinical groups or population-derived samples, estimates of enzyme activity in blood or, by positron emission tomography, in the brain and, most recently, measurement of methylation of the gene. Most of the studies converge in associating MAO-A and MAO-B with impulsive, aggressive or antisocial personality traits or behaviours, including alcohol-related problems, and for MAO-A available evidence strongly supports interaction with adverse environmental exposures in childhood. What is known about genotype effects, and on expression and activity of the enzyme in the brain and in blood has not yet been possible to unite into a mechanistic model of the role of monoamine systems, but the reason for this low degree of generalization is likely caused by the cross-sectional nature of investigation that has not incorporated the developmental effects of MAO-s in critical time windows, including the foetal period. The "risk variants" of both MAO-s appear to increase behavioural plasticity, as supportive environments may particularly well enhance the hidden potential of their carriers. Importantly, male and female brain and behaviours have been found very different with regard to MAO x life events interaction. Future studies need to take into consideration these developmental aspects and sex/gender, as well as to specify the role of different types of environmental factors.

  • 31.
    Hellgren, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Allopregnanolone levels and depressive symptoms during pregnancy in relation to single nucleotide polymorphisms in the allopregnanolone synthesis pathway2017In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 94, p. 106-113Article in journal (Refereed)
    Abstract [en]

    Allopregnanolone, a neurosteroid whose levels rise throughout gestation, putatively stabilizes antenatal mood. The present study aimed to investigate associations of plasma allopregnanolone to antenatal depressive symptoms, as well as to genetic and obstetric factors. Allopregnanolone plasma levels from 284 pregnant women were measured around gestational week 18. Haplotype tag single nucleotide polymorphisms in the aldo-keto reductase family 1, members C2 and C4 (AKR1C2, AKR1C4), and steroid 5 alpha-reductase 1 and 2 (SRD5A1, and SRD5A2) genes were genotyped in a larger sample of pregnant women (n=1351). The Edinburgh Postnatal Depression Scale (EPDS) was administered via web-questionnaires in gestational weeks 17 and 32. Demographic and obstetric data was retrieved from web-questionnaires and medical records. There was no association between allopregnanolone levels and depressive symptoms. Furthermore, no associations between allopregnanolone level and synthesis pathway genotypes were found after accounting for multiple comparisons. However, exploratory analyses suggested that the women who were homozygous for the minor allele of the AKR1C2 polymorphism rs1937863 had nominally lower allopregnanolone levels and lower depression scores in gestational week 17, but also the highest increase in depression scores between week 17 and 32. Additionally, higher body mass index was associated with lower allopregnanolone levels. The results do not support second trimester plasma allopregnanolone as a mood stabilizing factor. However, we speculate that AKR1C2 variation may alter the susceptibility to depressive symptoms through effects on central allopregnanolone synthesis. Another implication of this study is that the relationship between neuroactive steroids and obesity in pregnancy deserves to be investigated.

  • 32. Höflich, Anna
    et al.
    Savli, Markus
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Moser, Ulrike
    Novak, Klaus
    Kasper, Siegfried
    Lanzenberger, Rupert
    Neuropsychiatric deep brain stimulation for translational neuroimaging2013In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 79, no 1, p. 30-41Article in journal (Refereed)
    Abstract [en]

    From a neuroimaging point of view, deep brain stimulation (DBS) in psychiatric disorders represents a unique source of information to probe results gained in functional, structural and molecular neuroimaging studies in vivo. However, the implementation has, up to now, been restricted by the heterogeneity of the data reported in DBS studies. The aim of the present study was therefore to provide a comprehensive and standardized database of currently used DBS targets in selected psychiatric disorders (obsessive–compulsive disorder (OCD), treatment-resistant depression (TRD), Gilles de la Tourette syndrome (GTS)) to enable topological comparisons between neuroimaging results and stimulation areas. A systematic literature research was performed and all peer-reviewed publications until the year 2012 were included. Literature research yielded a total of 84 peer-reviewed studies including about 296 psychiatric patients. The individual stimulation data of 37 of these studies meeting the inclusion criteria which included a total of 202 patients (63 OCD, 89 TRD, 50 GTS) was translated into MNI stereotactic space with respect to AC origin in order to identify key targets.

    The created database can be used to compare DBS target areas in MNI stereotactic coordinates with: 1) activation patterns in functional brain imaging (fMRI, phfMRI, PET, MET, EEG); 2) brain connectivity data (e.g., MR-based DTI/tractography, functional and effective connectivity); 3) quantitative molecular distribution data (e.g., neuroreceptor PET, post-mortem neuroreceptor mapping); 4) structural data (e.g., VBM for neuroplastic changes). Vice versa, the structural, functional and molecular data may provide a rationale to define new DBS targets and adjust/fine-tune currently used targets in DBS based on this overview in stereotactic coordinates. Furthermore, the availability of DBS data in stereotactic space may facilitate the investigation and interpretation of treatment effects and side effect of DBS by comparing these to neuroimaging results. The present study thus improves comparability between functional, structural and molecular data in standard stereotactic space gained in neuroimaging studies with surgical targets for DBS, which is among other possible implications of crucial importance for the definition of new targets for effective DBS.

  • 33.
    Iliadis, Stavros I.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Sylven, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström, Inger Poromaa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 8, article id e0135471Article in journal (Refereed)
    Abstract [en]

    Background The biology of peripartum depression remains unclear, with altered stress and the Hypothalamus- Pituitary-Adrenal axis response having been implicated in its pathophysiology. Methods The current study was undertaken as a part of the BASIC project (Biology, Affect, Stress, Imaging, Cognition), a population-based longitudinal study of psychological wellbeing during pregnancy and the postpartum period in Uppsala County, Sweden, in order to assess the association between evening salivary cortisol levels and depressive symptoms in the peripartum period. Three hundred and sixty-five pregnant women from the BASIC cohort were recruited at pregnancy week 18 and instructed to complete a Swedish validated version of the Edinburgh Postnatal Depression Scale at the 36th week of pregnancy as well as the sixth week after delivery. At both times, they were also asked to provide evening salivary samples for cortisol analysis. A comprehensive review of the relevant literature is also provided. Results Women with postpartum EPDS score >= 10 had higher salivary evening cortisol at six weeks postpartum compared to healthy controls (median cortisol 1.19 vs 0.89 nmol/L). A logistic regression model showed a positive association between cortisol levels and depressive symptoms postpartum (OR = 4.1; 95% CI 1.7-9.7). This association remained significant even after controlling for history of depression, use of tobacco, partner support, breastfeeding, stressful life events, and sleep problems, as possible confounders (aOR = 4.5; 95% CI 1.5-14.1). Additionally, women with postpartum depressive symptoms had higher postpartum cortisol levels compared to both women with depressive symptoms antenatally and controls (p = 0.019 and p = 0.004, respectively). Conclusions Women with depressive symptoms postpartum had higher postpartum cortisol levels, indicating an altered response of the HPA-axis in postpartum depression.

  • 34.
    Iliadis, Stavros I.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sylvén, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Jocelien, O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hannefors, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Elfström, Dick
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Corticotropin-releasing hormone and postpartum depression: a longitudinal study2015In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 30, p. 351-352Article in journal (Other academic)
  • 35.
    Iliadis, Stavros
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sylvén, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Jocelien, Olivier
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hannefors, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Elfström, Dick
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Corticotropin-releasing hormone and postpartum depression: A longitudinal study2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 61, p. 61-61Article in journal (Other academic)
  • 36.
    Isaksson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry. Karolinska Inst, Ctr Neurodev Disorders, Karolinska Inst KIND, Dept Womens & Childrens Hlth,Pediat Neuropsychiat, S-17177 Stockholm, Sweden.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Rehn, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Tuvblad, Catherine
    Department of Psychology, University of Southern California, CA 90089-1061, USA;School of Law, Psychology and Social Work, Örebro University, 701 82 Örebro, Sweden.
    Andershed, Henrik
    School of Law, Psychology and Social Work, Örebro University, 701 82 Örebro, Sweden.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Associations between the FKBP5 haplotype, exposure to violence and anxiety in females2016In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 72, p. 196-204Article in journal (Refereed)
    Abstract [en]

    The gene that encodes the FK506-binding protein 5 (FKBP5) is regarded as a candidate for investigating how negative life events interact with a genetic predisposition to stress-related disorders, such as depression and anxiety. Given the role of FKBP5 as an important regulator of stress responses, we aimed to investigate if single-nucleotide polymorphisms (SNPs) in FKBP5-in the presence/absence of exposure to violence-are associated with symptoms of depression and anxiety. Data from two community-based samples of adolescents (n=1705) and young adults (n=1800) regarding ratings on depression, anxiety, exposure to violence and FKBP5 genotype were collected. A risk haplogenotype including the minor alleles of seven common SNPs in the FKBP5 (rs3800373, rs9296158, rs7748266, rs1360780, rs9394309, rs9470080 and rs4713916) conferred higher ratings on anxiety among females, but not males, in the presence of violence. Exposure to violence and female sex were associated with higher ratings on both depression and anxiety, with the exception of ratings on depression among young adults, on which sex had no effect. Ratings on depression were not associated with the haplogenotype. These findings may correspond to differences in the regulation of the HPA axis and with the higher vulnerability to anxiety in females.

  • 37.
    Isaksson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Grigorenko, Elena L
    Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.; Moscow MV Lomonosov State Univ, Moscow, Russia.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Af Klinteberg, Britt
    Stockholm Univ, Stockholm, Sweden.; Karolinska Inst, Stockholm, Sweden.
    Koposov, Roman A
    Univ Tromso, Tromso, Norway.
    Ruchkin, Vladislav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.; Sater Forens Psychiat Clin, Sater, Sweden.
    Exploring possible association between DβH genotype (C1021T), early onset of conduct disorder and psychopathic traits in juvenile delinquents.2016In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491, Vol. 266, no 8, p. 771-773Article in journal (Refereed)
    Abstract [en]

    Early onset of conduct disorder (CD) with callous-unemotional traits has been linked to low levels of dopamine β-hydroxylase (DβH), an enzyme involved in dopamine turnover. The C1021T polymorphism in the DβH gene is a major quantitative-trait locus, regulating the level of DβH. In this study of juvenile delinquents from Northern Russia (n = 180), the polymorphism at -1021 was associated neither with early-onset CD nor with psychopathic traits. Association was found between psychopathic traits and early-onset CD, ADHD and mania.

  • 38.
    Jokinen, Jussi
    et al.
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Umea Univ, Dept Clin Sci, Umea, Sweden..
    Königsson, Johan
    Umea Univ, Dept Clin Sci, Umea, Sweden..
    Moberg, Tomas
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Jönsson, Erik G.
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, NORMENT, Oslo, Norway..
    Tiihonen, Jari
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Univ Eastern Finland, Niuvanniemi Hosp, Dept Forens Psychiat, Kuopio, Finland..
    Nordström, Peter
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Åsberg, Marie
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Platelet monoamine oxidase activity and interpersonal violence in male suicide attempters2018In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 260, p. 173-176Article in journal (Refereed)
    Abstract [en]

    Low platelet monoamine oxidase B (MAO-B) activity, proxy of low central serotonergic functions, has been shown to correlate with criminal behavior in adolescents that come from an unfavorable psychosocial environment but not in adolescents from good conditions, indicating a link between environment, MAO-B activity and aggressive behavior. The purpose of this study was to examine the association between MAO-B activity and lifetime interpersonal violence in suicide attempters. The study included a total of 28 suicide attempters (18 men and 10 women). Assessments of childhood exposure to and expressed interpersonal violence during childhood and as an adult were carried out with the Karolinska Interpersonal Violence Scale (KIVS). Platelet MAO-B activity was measured with 2-phenylethylamine (b-PEA) as substrate. Broken down by gender, the correlations between platelet MAO-B activity and both exposure scores to interpersonal violence as a child and expressed lifetime interpersonal violence were significant in male suicide attempters (r = -0.61, p = 0.035; r = - 0.84, p = 0.0005), but not in women. Our finding of significant associations between interpersonal violence and low MAO-B activity need to be replicated in other cohorts of suicide attempters.

  • 39.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp..
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nordeman, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Wilking, H.
    Uppsala Univ Hosp..
    De Grauw, Haro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Takahashi, K.
    RIKEN Ctr Life Sci Technol..
    Antoni, G.
    Uppsala Univ Hosp..
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp..
    Tracer kinetic analysis of [C-11] Cetrozole as a PET tracer for aromatase in the human brain2017In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, p. 71-72Article in journal (Other academic)
  • 40.
    Kallak, Theodora Kunovac
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Sandelin-Francke, Lotta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Ubhayasekera, Kumari
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Campbell, Rebecca E
    Centre for Neuroendocrinology, Department of Physiology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Maternal and female fetal testosterone levels are associated with maternal age and gestational weight gain2017In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 177, no 4, p. 379-388Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Prenatal androgen exposure has been suggested to play a role in polycystic ovary syndrome. Given the limited information on what maternal characteristics influence maternal testosterone levels, and the even less explored routes by which female fetus androgen exposure would occur, the aim of this study was to investigate the impact of maternal age, BMI, weight gain, depressed mood and aromatase SNPs on testosterone levels in maternal serum and amniotic fluid of female fetuses.

    METHODS: Blood samples from pregnant women (n = 216) obtained in gestational weeks 35-39, and pre-labor amniotic fluid samples from female fetuses (n = 56), taken at planned Caesarean section or in conjunction with amniotomy for induction of labor, were analyzed. Maternal serum testosterone and amniotic fluid testosterone and cortisol were measured by tandem mass spectrometry.

    RESULTS: Multiparity (β = -0.28, P < 0.001), self-rated depression (β = 0.26, P < 0.001) and weight gain (β = 0.18, P < 0.05) were independent explanatory factors for the maternal total testosterone levels. Maternal age (β = -0.34, P < 0.001), weight gain (β = 0.19, P < 0.05) and amniotic fluid cortisol levels (β = 0.44, P < 0.001) were independent explanatory factors of amniotic fluid testosterone in female fetuses, explaining 64.3% of the variability in amniotic fluid testosterone.

    WIDER IMPLICATIONS OF THE FINDINGS: Young maternal age and excessive maternal weight gain may increase the prenatal androgen exposure of female fetuses. Further studies are needed to explore this finding.

  • 41.
    Nilsson, Kent W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hodgins, Sheilagh
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Genotypes do not confer risk for delinquency but rather alter susceptibility to positive and negative environmental factors: Gene-environment interactions of BDNF Val66Met, 5-HTTLPR, and MAOA-uVNTR2015In: International Journal of Neuropsychopharmacology, ISSN 1461-1457, E-ISSN 1469-5111, Vol. 18, no 5Article in journal (Refereed)
    Abstract [en]

    Background. Previous evidence of gene-by-environment interactions associated with emotional and behavioral disorders is contradictory. Differences in findings may result from variation in valence and dose of the environmental factor, and/or failure to take account of gene-by-gene interactions. The present study investigated interactions between the brain-derived neurotrophic factor gene (BDNF Val66Met), the serotonin transporter gene linked polymorphic region (5-HTTLPR), the monoamine oxidase A (MAOA-uVNTR) polymorphisms, family conflict, sexual abuse, the quality of the child-parent relationship, and teenage delinquency.

    Methods. In 2006, as part of the Survey of Adolescent Life in Västmanland, Sweden, 1337 high-school students, aged 17-18 years, anonymously completed questionnaires and provided saliva samples for DNA analyses.

    Results. Teenage delinquency was associated with two-, three-, and four-way interactions of each of the genotypes and the three environmental factors. Significant four-way interactions were found for BDNF Val66Met×5-HTTLPR×MAOA-uVNTR×family conflicts, and for BDNF Val66Met×5-HTTLPR×MAOA-uVNTR×sexual abuse. Further, the two genotype combinations that differed the most in expression levels (BDNF Val66Met Val, 5-HTTLPR LL, MAOA-uVNTR LL (girls) and L (boys) vs BDNF Val66Met Val/Met, 5-HTTLPR S/LS, MAOA-uVNTR S/SS/LS) in interaction with family conflict and sexual abuse were associated with the highest delinquency scores. The genetic variants previously shown to confer vulnerability for delinquency (BDNF Val66Met Val/Met×5-HTTLPR S×MAOA-uVNTR S) were associated with the lowest delinquency scores in interaction with a positive child-parent relationship.

    Conclusions. Functional variants of the MAOA-uVNTR, 5-HTTLPR, and BDNF Val66Met, either alone or in interaction with each other, may be best conceptualized as modifying sensitivity to environmental factors that confer either risk or protection for teenage delinquency.

  • 42.
    Nilsson, Kent W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Sonnby, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nordquist, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Comasco, Erica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Sjöberg, Richard L
    Transcription Factor Activating Protein-2β (TFAP-2β) genotype and symptoms of attention deficit hyperactivity disorder in relation to symptoms of depression in two independent samples2014In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 23, no 4, p. 207-217Article in journal (Refereed)
    Abstract [en]

    The Transcription Factor Activating Protein-2β (TFAP-2β) gene has been shown to influence monoaminergic neurotransmission, and several genes important for monoaminergic function have binding sites for TFAP-2β. Familial studies of attention deficit hyperactivity disorder (ADHD) suggest a hereditary-determined subtype of ADHD with comorbid depression. We examined a functional variation of the TFAP-2β gene in the context of co-occurring symptoms of ADHD and depression in two independent population-based samples of adolescents (Group A, n = 175 and Group B, n = 1,506) from Sweden. Results indicated 6.1 to 7.8 % of adolescents screened positively for ADHD and depression symptoms. Symptoms of depression were more common among girls who screened positively for ADHD and did not carry the nine-repeat allele of the TFAP-2β intron 1 Variable Number Tandem Repeat (VNTR) polymorphism. The presence of the nine-repeat variant of the TFAP-2β intron 1 VNTR appears to protect girls with ADHD symptoms from the co-expression of symptoms of depression.

  • 43.
    Nylander, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Palm, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Daoura, Loudin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Rowley, Samuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Roman, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Early Life Stress Causes Long Term Effects On Neuropeptides, Alcohol Consumption And Behaviour: Results From A Translational Initiative2014In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 38, p. 355A-355AArticle in journal (Other academic)
  • 44.
    Nylander, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Palm, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Daoura, Loudin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Rowley, Samuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Roman, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Neurobiological and behavioural studies on early life stress and adolescent alcohol drinking in a translational initiative2014In: Alcohol, ISSN 0741-8329, E-ISSN 1873-6823, Vol. 48, no 2, p. 160-161Article in journal (Other academic)
  • 45.
    Nylander, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Vrettou, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Bendre, Megha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Boon, Wout
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Andershed, Henrik
    Tuvblad, Catherine
    Nilsson, Kent W
    Centre for Clinical Research, Västerås Central Hospital, Västerås, Sweden.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans2017In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 54, no 8, p. 6225-6234Article in journal (Refereed)
    Abstract [en]

    Alcohol misuse has been linked to dysregulation of stress, emotion, and reward brain circuitries. A candidate key mediator of this association is the FK506-binding protein (FKBP5), a negative regulator of the glucocorticoid receptor. The aim of the present study was to further understand the Fkbp5/FKBP5-related genetic underpinnings underlying the relationship between early life social relations and alcohol drinking. The effect of maternal separation and voluntary alcohol drinking on Fkbp5 expression was investigated in the brain of young adult rats, whereas the interaction effect of the functional FKBP5 single nucleotide polymorphism rs1360780 genotype and parent-child relationship on problematic drinking was examined in young adult humans. In rats, Fkbp5 expression in the nucleus accumbens and ventral tegmental area, core regions of the reward system, was affected in a region-dependent manner and in opposite direction by maternal separation and alcohol drinking. Fkbp5 expression in the cingulate cortex was affected by the combined effect of maternal separation and alcohol drinking. In humans, the TT genotype, in the presence of a poor relationship between the child and parents, was associated with problematic drinking behavior. The present findings suggest that Fkbp5 expression in mesocorticolimbic dopaminergic regions associates with early life stress-mediated sensitivity to alcohol drinking and that FKBP5 genotype interacts with parent-child relationship to influence alcohol drinking. These findings are the first to point to a role of FKBP5 in propensity to alcohol misuse and call for studies of the underlying molecular mechanisms to identify potential drug targets.

  • 46.
    Olofsdotter, Susanne