uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 92) Show all publications
Joost, U., Villa, I., Comasco, E., Oreland, L., Veidebaum, T. & Harro, J. (2019). Association between Transcription Factor AP-2B genotype, obesity, insulin resistance and dietary intake in a longitudinal birth cohort study. International Journal of Obesity, 43(10), 2095-2106
Open this publication in new window or tab >>Association between Transcription Factor AP-2B genotype, obesity, insulin resistance and dietary intake in a longitudinal birth cohort study
Show others...
2019 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 43, no 10, p. 2095-2106Article in journal (Refereed) Published
Abstract [en]

Background The development of obesity has a large genetic component, and the gene encoding the transcription factor 2 beta (TFAP2B) has been identified as one of the responsible factors. We investigated the effect of TFAP2B intron 2 variable number tandem repeat (VNTR) genotype on obesity, insulin resistance and dietary intake from 15 to 33 years of age. Methods The sample included both birth cohorts (originally n = 1176) of the longitudinal Estonian Children Personality Behaviour and Health Study. The association between TFAP2B genotype, and anthropometric measurements, glucose metabolism and dietary intake at ages 15, 18 and 25 years was assessed using the linear mixed-effects regression models. Differences in anthropometric measurements, biochemical measures, blood pressure and dietary intake between TFAP2B genotypes at different age, including data of the older cohort at age 33, were assessed by one-way ANOVA. Results Male homozygotes for the TFAP2B 5-repeat allele had significantly higher body weight, body mass index, sum of 5 skinfolds, proportion of body fat, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, fasting insulin and HOMA index. In female subjects, homozygotes for the TFAP2B 5-repeat allele had significantly larger increase in the rate of change per year in body weight, body mass index and hip circumference between years 15 and 25. By age 33, the findings were similar. A decrease in daily energy intake from adolescence to young adulthood was observed. In males, heterozygotes had significantly smaller decrease in the rate of change per year in daily energy intake. Conclusions The association of TFAP2B with the development of obesity and insulin resistance is present throughout adolescence to young adulthood in males. In females the effect of TFAP2B on obesity appears later, in young adulthood. The TFAP2B effect is rather related to differences in metabolism than energy intake.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-395721 (URN)10.1038/s41366-019-0396-y (DOI)000488494400023 ()31209268 (PubMedID)
Funder
Swedish Research Council, VR: 2015-00495
Available from: 2019-10-24 Created: 2019-10-24 Last updated: 2019-10-24Bibliographically approved
Comasco, E., Schijven, D., de Maeyer, H., Vrettou, M., Nylander, I., Sundström-Poromaa, I. & Olivier, J. D. A. (2019). Constitutive serotonin transporter reduction resembles maternal separation with regard to stress-related gene expression. ACS Chemical Neuroscience, 10(7), 3132-3142
Open this publication in new window or tab >>Constitutive serotonin transporter reduction resembles maternal separation with regard to stress-related gene expression
Show others...
2019 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 10, no 7, p. 3132-3142Article in journal (Refereed) Published
Abstract [en]

Interactive effects between allelic variants of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) and stressors on depression symptoms have been documented, as well as questioned, by meta-analyses. Translational models of constitutive 5-htt reduction and experimentally controlled stressors often led to inconsistent behavioral and molecular findings and often did not include females. The present study sought to investigate the effect of 5-htt genotype, maternal separation, and sex on the expression of stress-related candidate genes in the rat hippocampus and frontal cortex. The mRNA expression levels of Avp, Pomc, Crh, Crhbp, Crhr1, Bdnf, Ntrk2, Maoa, Maob, and Comt were assessed in the hippocampus and frontal cortex of 5-htt± and 5-htt+/+ male and female adult rats exposed, or not, to daily maternal separation for 180 min during the first 2 postnatal weeks. Gene- and brain region-dependent, but sex-independent, interactions between 5-htt genotype and maternal separation were found. Gene expression levels were higher in 5-htt+/+ rats not exposed to maternal separation compared with the other experimental groups. Maternal separation and 5-htt+/− genotype did not yield additive effects on gene expression. Correlative relationships, mainly positive, were observed within, but not across, brain regions in all groups except in non-maternally separated 5-htt+/+ rats. Gene expression patterns in the hippocampus and frontal cortex of rats exposed to maternal separation resembled the ones observed in rats with reduced 5-htt expression regardless of sex. These results suggest that floor effects of 5-htt reduction and maternal separation might explain inconsistent findings in humans and rodents.

Keywords
Frontal cortex, hippocampus, maternal separation, serotonin transporter, gene expression
National Category
Neurosciences Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-381818 (URN)10.1021/acschemneuro.8b00595 (DOI)000476685400012 ()30614673 (PubMedID)
Funder
Swedish Society of Medicine, SLS-411161Fredrik och Ingrid Thurings StiftelseLars Hierta Memorial FoundationSwedish Research Council, K2012-61X-22090-01-3Swedish Research Council, VR: 2015-00495EU, FP7, Seventh Framework Programme, INCA 600398Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-09-20Bibliographically approved
Bendre, M., Granholm, L., Drennan, R., Meyer, A., Yan, L., Nilsson, K. W., . . . Comasco, E. (2019). Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats.. Alcohol, 79, 7-16
Open this publication in new window or tab >>Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats.
Show others...
2019 (English)In: Alcohol, ISSN 0741-8329, E-ISSN 1873-6823, Vol. 79, p. 7-16Article in journal (Refereed) Published
Abstract [en]

Early life stress (ELS) or alcohol consumption can influence DNA methylation and affect gene expression. The monoamine oxidase A (Maoa) encodes the enzyme that metabolizes monoaminergic neurotransmitters crucial for the stress response, alcohol reward, and reinforcement. Previously, we reported lower Maoa expression in the nucleus accumbens and dorsal striatum of male rats exposed to ELS during the first three postnatal weeks, and to voluntary alcohol consumption in adulthood, compared with controls. The present study continued to investigate the effect of ELS and alcohol consumption on Maoa methylation, and its relation to Maoa expression in these animals. We selected candidate CpGs after performing next-generation bisulfite sequencing of the Maoa promoter, intron 1-5, exons 5 and 6, together comprised of 107 CpGs, in a subgroup of rats. Pyrosequencing was used to analyse the methylation of ten candidate CpGs in the promoter and intron 1 in the entire sample. ELS and alcohol displayed an interaction effect on CpG-specific methylation in the dorsal striatum. CpG-specific methylation correlated with Maoa expression, corticosterone levels, and alcohol consumption in a brain region-specific manner. CpG-specific methylation in the Maoa promoter was a potential moderator of the interaction of ELS with alcohol consumption on Maoa expression in the NAc. However, the findings were sparse, did not survive correction for multiple testing, and the magnitude of differences in methylation levels was small. In conclusion, CpG-specific Maoa methylation in the promoter and intron 1 may associate with ELS, alcohol consumption and Maoa expression in reward-related brain regions.

Keywords
Alcohol, DNA methylation, Gene expression, Maoa, Maternal separation, Stress
National Category
Psychiatry Neurosciences
Identifiers
urn:nbn:se:uu:diva-368636 (URN)10.1016/j.alcohol.2018.11.001 (DOI)000483450600002 ()30414913 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2011-0627Fredrik och Ingrid Thurings StiftelseLars Hierta Memorial FoundationThe Swedish Brain Foundation, PS2013-0052Swedish Research Council, K2012-61X-22090-01-3Swedish Research Council, VR: 2015-00495EU, FP7, Seventh Framework Programme, INCA 600398Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2018-12-06 Created: 2018-12-06 Last updated: 2019-10-17Bibliographically approved
Breedh, J., Comasco, E., Hellgren, C., Papadopoulos, F. C., Skalkidou, A. & Sundström Poromaa, I. (2019). Hypothalamic-pituitary-adrenal axis responsiveness, startle response, and sensorimotor gating in late pregnancy. Psychoneuroendocrinology, 106, 1-8
Open this publication in new window or tab >>Hypothalamic-pituitary-adrenal axis responsiveness, startle response, and sensorimotor gating in late pregnancy
Show others...
2019 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 106, p. 1-8Article in journal (Refereed) Published
Abstract [en]

During pregnancy, the hypothalamic-pituitary-adrenal (HPA) axis, the main regulator of the stress response, undergoes dramatic changes. The acoustic startle response (ASR) and the prepulse inhibition (PPI) of the startle response are neurophysiological research tools and objective measures of an individual's response to an emotional context or stressor. The ASR and PPI are influenced by psychiatric diseases characterized by anxiety symptoms and are sensitive to cortisol. Hence, the ASR and the PPI can be used to investigate the effects of pregnancy-induced endocrine changes and their contribution to affective disorders. The present study sought to investigate the association between measures of HPA-axis responsiveness, startle reactivity and sensorimotor gating during pregnancy that to date remains unknown. The eye-blink component of the ASR, and its prepulse inhibition, were measured in 107 late third trimester pregnant women. Saliva samples were collected to assess the cortisol awakening response (CAR), a measure of HPA-axis activity. Blood was sampled to measure serum levels of cortisol, cortisone and the cortisone to cortisol ratio. Ongoing anxiety disorders, sleep duration, smoking, and age were considered as potential confounders in the statistical analyses. CAR reactivity, measured as area under the curve (AUC) increase and above baseline, was positively associated with baseline startle magnitude [Cohen's d = 0.27; F (1, 105) = 4.99; p = 0.028, and Cohen's d = 0.30; F (1, 105) = 6.25; p = 0.014, respectively] as well as PPI at 86 dB [Cohen's d = 0.29; F (1, 105) = 5.93; p = 0.017; and Cohen's d = 0.34; F (1, 105) = 8.38; p = 0.005, respectively]. The observed positive correlation between startle magnitude in pregnant women and greater increase in cortisol during the awakening response may be interpreted as heightened neurophysiological reactivity, likely associated with dysregulation of the stress system.

Keywords
AUC, CAR, Cortisol, Pregnancy, Sensorimotor gating, Startle response
National Category
Endocrinology and Diabetes Neurosciences Psychiatry
Identifiers
urn:nbn:se:uu:diva-381815 (URN)10.1016/j.psyneuen.2019.03.008 (DOI)000474678300001 ()30927623 (PubMedID)
Funder
Swedish Research Council, 521-2013-2339Marianne and Marcus Wallenberg Foundation, MMW2011.0115The Swedish Medical Association, SLS-250581Swedish Society of Medicine, SLS-331991Swedish Research Council, 2015-00495EU, FP7, Seventh Framework Programme, INCA 600398
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-08-16Bibliographically approved
Sundström Poromaa, I., Comasco, E., Bäckström, T., Bixo, M., Jensen, P. & Frokjaer, V. G. (2019). Negative Association Between Allopregnanolone and Cerebral Serotonin Transporter Binding in Healthy Women of Fertile Age. Frontiers in Psychology, 9, Article ID 2767.
Open this publication in new window or tab >>Negative Association Between Allopregnanolone and Cerebral Serotonin Transporter Binding in Healthy Women of Fertile Age
Show others...
2019 (English)In: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 9, article id 2767Article in journal (Refereed) Published
Abstract [en]

Allopregnanolone is a metabolite of the sex hormone progesterone, with suggested relevance for female mood disorders. While allopregnanolone and serotonin are known to influence psychological well-being, the molecular and psychological specifics of their relationship are to date poorly understood, especially in women of fertile age who experience regular fluctuations of progesterone across the menstrual cycle. Availability of serotonin in the synaptic cleft is regulated by the serotonin transporter (SERT), which can be imaged in the living human brain by use of positron emission tomography (PET) and the radiotracer [C-11]DASB. To evaluate sex-specific allopregnanolone-SERT interactions, the present study investigated the relationship between cerebral SERT availability, serum allopregnanolone levels and psychological well-being in women of fertile age. Brain imaging data, self-reported symptoms of mental distress and emotion regulation, and biobank material from ninety healthy women were available from the Center for Integrated Molecular Brain Imaging (CIMBI) database. Age, BMI, and daylight minutes were included as covariates in the analyses and SERT genotype (5-HTTLPR) was considered a potential confounder. Lower serum allopregnanolone levels were associated with higher SERT binding in the prefrontal cortex. Moreover, allopregnanolone levels were negatively associated with measures of alertness, although this finding was not mediated by prefrontal cortex SERT binding. These findings suggest a link between the typical psychological well-being experienced in the follicular phase when allopregnanolone levels are low and higher SERT in the prefrontal cortex, a region for higher cognitive functions and top-down regulation of emotions.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2019
Keywords
allopregnanolone, brain, mood, PET, serotonin transporter, women, 5HTT
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-375873 (URN)10.3389/fpsyg.2018.02767 (DOI)000455554400001 ()30687199 (PubMedID)
Funder
Swedish Research CouncilEU, FP7, Seventh Framework Programme, INCA 600398Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04Bibliographically approved
Skalkidou, A., Sundström Poromaa, I., Iliadis, S. I., Huizink, A. C., Hellgren, C., Freyhult, E. & Comasco, E. (2019). Stress-related genetic polymorphisms in association with peripartum depression symptoms and stress hormones: A longitudinal population-based study. Psychoneuroendocrinology, 103, 296-305
Open this publication in new window or tab >>Stress-related genetic polymorphisms in association with peripartum depression symptoms and stress hormones: A longitudinal population-based study
Show others...
2019 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 103, p. 296-305Article in journal (Refereed) Published
Abstract [en]

Individual differences in the response of the stress system to hormonal changes during pregnancy and the postpartum period render some women susceptible to developing depression. The present study sought to investigate peripartum depression and stress hormones in relation to stress-related genotypes. The Edinburgh Postnatal Depression Scale was used to assess peripartum depressive symptoms in a sample of 1629 women, followed from pregnancy week seventeen to six months postpartum. Genotypes of ninety-four haplotype-tag single nucleotide polymorphisms (SNPs) in sixteen genes of the hypothalamus-pituitary-adrenal axis pathway were analyzed and data on psychosocial and demographic factors was collected. In sub-studies, salivary cortisol awakening response in gestational week 35-39, salivary evening cortisol levels in gestational week 36 and postpartum week 6, and blood cortisol and cortisone levels in gestational week 35-39 were analyzed. SNP-set kernel association tests were performed at the gene-level, considering psychosocial and demographic factors, followed by post-hoc analyses of SNPs of significant genes. Statistically significant findings at the 0.05 p-level included SNPs in the hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) gene in relation to self-rated depression scores in postpartum week six among all participants, and serpin family A member 6 (SERPINA6) gene at the same time-point among women with de novo onset of postpartum depression. SNPs in these genes also associated with stress hormone levels during pregnancy. The present study adds knowledge to the neurobiological basis of peripartum depression by systematically assessing SNPs in stress-regulatory genes and stress-hormone levels in a population-based sample of women.

Keywords
Cortisol, Gene, Hormones, Hypothalamic-pituitary-adrenal axis, Perinatal depression, Postpartum depression, Single nucleotide polymorphism, Stress
National Category
Endocrinology and Diabetes Psychiatry
Identifiers
urn:nbn:se:uu:diva-381817 (URN)10.1016/j.psyneuen.2019.02.002 (DOI)000465367000038 ()30776573 (PubMedID)
Funder
Swedish Research Council, 521-2013-2339Marianne and Marcus Wallenberg Foundation, MMW2011.0115The Swedish Medical Association, SLS-250581Forte, Swedish Research Council for Health, Working Life and Welfare, 2011-0627Swedish Society of Medicine, SLS-331991Swedish Research Council, 2015-00495EU, FP7, Seventh Framework Programme, INCA 600398
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-06-18Bibliographically approved
Vrettou, M., Nilsson, K. W., Tuvblad, C., Rehn, M., Åslund, C., Andershed, A.-K., . . . Comasco, E. (2019). VGLUT2 rs2290045 genotype moderates environmental sensitivity to alcohol-related problems in three samples of youths. European Child and Adolescent Psychiatry, 28(10), 1329-1340
Open this publication in new window or tab >>VGLUT2 rs2290045 genotype moderates environmental sensitivity to alcohol-related problems in three samples of youths
Show others...
2019 (English)In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 28, no 10, p. 1329-1340Article in journal (Refereed) Published
Abstract [en]

The importance of Vesicular Glutamate Transporter 2 (VGLUT2)-mediated neurotransmission has been highlighted in studies on addiction-related phenotypes. The single nucleotide polymorphism rs2290045 in VGLUT2 has been associated with alcohol dependence, but it is unknown whether or how this association is affected by environmental factors. The present study determined whether the association of alcohol-related problems with the rs2290045 in the VGLUT2 gene was modified by negative and positive environmental factors. Three samples were included: a clinical sample of 131 adolescents followed from age 17 to 22; a general population sample of 1794 young adults; and a general population sample of 1687 adolescents followed from age 14 to 17. DNA was extracted from saliva and the rs2290045 (T/C) was genotyped. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test. Stressful life events (SLE) and parenting were assessed by questionnaires. Gene-environment interactions were investigated using a dual statistical approach. In all samples (effect sizes 0.6-6.2%), and consistent with the differential susceptibility framework, T carriers exposed to SLE reported more alcohol-related problems if they had experienced poor parenting, and lower alcohol-related problems if they had received supportive parenting. T carriers not exposed to SLE reported higher alcohol-related problems if they had received supportive parenting and lower alcohol-related problems if they had received poor parenting. Among CC carriers, alcohol-related problems did not vary as a function of negative and positive environmental factors. In conclusion, in three samples of youths, alcohol-related problems were associated with an interaction of VGLUT2 rs2290045, SLE, and parenting.

Keywords
Adolescents, Alcohol, Gene, Glutamate, Stress, VGLUT2
National Category
Psychiatry Medical Genetics
Identifiers
urn:nbn:se:uu:diva-381816 (URN)10.1007/s00787-019-01293-w (DOI)000489301800006 ()30805764 (PubMedID)
Funder
The Swedish Brain Foundation, PS2013-0052Åke Wiberg Foundation, M15-0239Forte, Swedish Research Council for Health, Working Life and Welfare, 2015-00897Swedish Research Council, 2013-4657Swedish Research Council, 2014-3804Swedish Research Council, VR: 2015-00495
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-11-06Bibliographically approved
Bendre, M., Comasco, E., Checknita, D., Tiihonen, J., Hodgins, S. & Nillson, K. W. (2018). Associations Between MAOA-uVNTR Genotype, Maltreatment, MAOA Methylation, and Alcohol Consumption in Young Adult Males. Alcoholism: Clinical and Experimental Research, 42(3), 508-519
Open this publication in new window or tab >>Associations Between MAOA-uVNTR Genotype, Maltreatment, MAOA Methylation, and Alcohol Consumption in Young Adult Males
Show others...
2018 (English)In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 42, no 3, p. 508-519Article in journal (Refereed) Published
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.

Keywords
Alcohol, DNA Methylation, Gene by Environment, MAOA-, uVNTR, Maltreatment
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-351264 (URN)10.1111/acer.13578 (DOI)000426489600005 ()29222910 (PubMedID)
Funder
Swedish Research Council, VR: 2015-00495
Available from: 2018-06-11 Created: 2018-06-11 Last updated: 2019-10-08Bibliographically approved
Checknita, D., Ekström, T. J., Comasco, E., Nilsson, K. W., Tiihonen, J. & Hodgins, S. (2018). Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women. Journal of neural transmission, 125(7), 1053-1064
Open this publication in new window or tab >>Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women
Show others...
2018 (English)In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 125, no 7, p. 1053-1064Article in journal (Refereed) Published
Abstract [en]

Childhood physical abuse (PA) and sexual abuse (SA) interact with monoamine oxidase A (MAOA) gene polymorphism to modify risk for mental disorders. In addition, PA and SA may alter gene activity through epigenetic mechanisms such as DNA methylation, thereby further modifying risk for disorders. We investigated whether methylation in a region spanning the MAOA first exon and part of the first intron was associated with PA and/or SA, MAOA genotype, alcohol dependence, drug dependence, depression disorders, anxiety disorders, and conduct disorder. 114 Swedish women completed standardized diagnostic interviews and questionnaires to report PA and SA, and provided saliva samples for DNA extraction. DNA was genotyped for MAOA-uVNTR polymorphisms, and methylation of a MAOA region of interest (chrX: 43,515,544-43,515,991) was measured. SA, not PA, was associated with hypermethylation of the MAOA first exon relative to no-abuse, and the association was robust to adjustment for psychoactive medication, alcohol and drug dependence, and current substance use. SA and MAOA-uVNTR genotype, but not their interaction, was associated with MAOA methylation. SA associated with all measured mental disorders. Hypermethylation of MAOA first exon mediated the association of SA with current depression, and both methylation levels and SA independently predicted lifetime depression. Much remains to be learned about the independent effects of SA and MAOA-uVNTR genotypes on methylation of the MAOA first exon.

Place, publisher, year, edition, pages
SPRINGER WIEN, 2018
Keywords
Child abuse, Depression, Epigenetics, Gene-environment interaction methylation, Women
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-358274 (URN)10.1007/s00702-018-1875-3 (DOI)000435405600006 ()29600412 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareStockholm County CouncilThe Karolinska Institutet's Research Foundation
Available from: 2018-08-30 Created: 2018-08-30 Last updated: 2018-08-30Bibliographically approved
Olofsdotter, S., Åslund, C., Furmark, T., Comasco, E. & Nilson, K. W. (2018). Differential susceptibility effects of oxytocin gene (OXT) polymorphisms and perceived parenting on social anxiety among adolescents. Development and psychopathology (Print), 30(2), 449-459
Open this publication in new window or tab >>Differential susceptibility effects of oxytocin gene (OXT) polymorphisms and perceived parenting on social anxiety among adolescents
Show others...
2018 (English)In: Development and psychopathology (Print), ISSN 0954-5794, E-ISSN 1469-2198, Vol. 30, no 2, p. 449-459Article in journal (Refereed) Published
Abstract [en]

Social anxiety is one of the most commonly reported mental health problems among adolescents, and it has been suggested that parenting style influences an adolescent's level of anxiety. A context-dependent effect of oxytocin on human social behavior has been proposed; however, research on the oxytocin gene (OXT) has mostly been reported without considering contextual factors. This study investigated the interactions between parenting style and polymorphic variations in the OXT gene in association with social anxiety symptoms in a community sample of adolescents (n = 1,359). Two single nucleotide polymorphisms linked to OXT, rs4813625 and rs2770378, were genotyped. Social anxiety and perceived parenting style were assessed by behavioral questionnaires. In interaction models adjusted for sex, significant interaction effects with parenting style were observed for both variants in relation to social anxiety. The nature of the interactions was in line with the differential susceptibility framework for rs4813625, whereas for rs2770378 the results indicated a diathesis–stress type of interaction. The findings may be interpreted from the perspective of the social salience hypothesis of oxytocin, with rs4813625 affecting social anxiety levels along a perceived unsafe–safe social context dimension.

National Category
Neurosciences Psychology
Identifiers
urn:nbn:se:uu:diva-323574 (URN)10.1017/S0954579417000967 (DOI)000430924500006 ()28606214 (PubMedID)
Funder
Fredrik och Ingrid Thurings StiftelseThe Swedish Brain Foundation, F02015-0315Forte, Swedish Research Council for Health, Working Life and Welfare, FORTE 2015-00897Åke Wiberg Foundation, MI5-0239Swedish Research Council, VR 2015-00495EU, FP7, Seventh Framework Programme, INCA 600398Stiftelsen Söderström - Königska sjukhemmet, SLS-559921
Available from: 2017-06-08 Created: 2017-06-08 Last updated: 2019-04-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2174-2068

Search in DiVA

Show all publications