| 1. |
- Culverhouse, R. C., et al.
(författare)
-
Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression
- 2018
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:1, s. 133-142
-
Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.
|
|
| 2. |
- Isaksson, Johan, et al.
(författare)
-
Associations between the FKBP5 haplotype, exposure to violence and anxiety in females
- 2016
-
Ingår i: Psychoneuroendocrinology. - Oxford, United Kingdom : Elsevier. - 0306-4530 .- 1873-3360. ; 72, s. 196-204
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 3. |
- Tuvblad, Catherine, 1968-, et al.
(författare)
-
Physical and verbal aggressive behavior and COMT genotype : Sensitivity to the environment
- 2016
-
Ingår i: American Journal of Medical Genetics Part B. - Hoboken, USA : John Wiley & Sons. - 1552-4841 .- 1552-485X. ; 171:5, s. 708-718
-
Tidskriftsartikel (refereegranskat)abstract
- Catechol-O-methyltransferase (COMT) genotype has been implicated as a vulnerability factor for several psychiatric diseases as well as aggressive behavior, either directly, or in interaction with an adverse environment. The present study aimed at investigating the susceptibility properties of COMT genotype to adverse and favorable environment in relation to physical and verbal aggressive behavior. The COMT Val158Met polymorphism was genotyped in a Swedish population-based cohort including 1,783 individuals, ages 20-24 years (47% males). A significant three-way interaction was found, after correction for multiple testing, between COMT genotype, exposure to violence, and parent-child relationship in association with physical but not verbal aggressive behavior. Homozygous for the Val allele reported lower levels of physical aggressive behavior when they were exposed to violence and at the same time experienced a positive parent-child relationship compared to Met carriers. Thus, susceptibility properties of COMT genotype were observed in relation to physical aggressive behavior supporting the hypothesis that COMT genotypes are modifying the sensitivity to environment that confers either risk or protection for aggressive behavior. As these are novel findings, they warrant further investigation and replication in independent samples.
|
|
| 4. |
- Mohammad, Salahuddin
(författare)
-
Investigating mental health disorders in relation to job and living related factors
- 2023
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Job satisfaction plays an important role for life quality and health of working individuals. While studies have shown that self-reported mental health conditions such as stress, anxiety and depression are associated with job satisfaction, a large population-based study exploring and comparing self-reported physician posed diagnosed conditions and their association with job satisfaction and job tenure is missing. First study addresses the gap along with exploring the impact of the neurotic personality trait and other possible contributing factors.Individuals with autism spectrum disorder (ASD) experience lower well-being as demonstrated epidemiologically mostly for children and adolescents. Further etiological investigation of inclusive wellbeing, in terms of five wellbeing spectrum (5-WBS) traits including neuroticism, depression, loneliness, life satisfaction and positive affect, among adults with ASD may deepen the understanding. Seond study aims to investigate if a genetic predisposition for ASD is associated with 5-WBS traits using polygenic risk score (PRS) analysis.In the first study, sixteen mental health disorders diagnosed by physicians, categorized into four major groups were investigated in relation to employment status (108,711 participants) and in relation to job satisfaction and job tenure (34,808 participants). Analyses were performed using linear regression adjusted for age, sex, TDI, BMI, education, physical activity, work hours and neuroticism. In the second study, PRS for ASD were constructed in the UK Biobank (N = 337,423), based on the GWAS conducted by Psychiatric Genetics Consortium (18,381 cases, 27,969 comparisons) using PRSice-2. First study showed Neurotic & Stress Disorders, Eating Disorders and Other Mental Health Disorders were strongly associated with lower job satisfaction and shorter job tenure in both unadjusted and adjusted analyses. Neuroticism was strongly linked to job satisfaction but was not associated with job tenure. Second study showed, ASD PRS significantly predicted associations with all 5-WBS traits, showing a positive association with the negative WBS traits, neuroticism (max R2 = 0.04%, P < 1x10-4, AUC 0.51), depression (max R2 = 0.06%, P < 1x10-4, AUC 0.51), loneliness (max R2 = 0.04%, P < 1x10-4, AUC 0.51) and a negative association with the positive WBS traits, life satisfaction (max R2 = 0.08%, P < 1x10-4, AUC 0.56), positive affect (max R2 = 0.10%, P < 1x10-4, AUC 0.53).Findings of first study clarify the complex relationship of mental health with job satisfaction and job tenure which is very important to understand in designing measures to improve working life participation of individuals with mental health issues. The findings of second study suggest that adults carrying a high load of susceptible SNPs for ASD are more likely to show a decreased well-being.
|
|
| 5. |
- Sonnby, Karin, et al.
(författare)
-
Symptoms of ADHD and depression in a large adolescent population : Co-occurring symptoms and associations to experiences of sexual abuse
- 2011
-
Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 65:5, s. 315-322
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Symptoms of either attention-deficit hyperactivity disorder (ADHD) or depression constitute the most common reasons for contact with child and adolescent psychiatry. The development of psychiatric symptoms can be explained by a combination of environmental stress events and genetic vulnerability. One common form of environmental stress with high impact on health is sexual abuse.Aims: To investigate the prevalence and co-occurrence of symptoms of ADHD and depression in relation to experiences of sexual abuse in a large adolescent general population.Method: All 15- and 18-year-old students (n = 4910) in the Swedish county of Vestmanland answered a school-based screening instrument including the six-question ADHD self-rating scale (ASRS), the Depression Self-Rating Scale (DSRS) and questions relating to experiences of sexual abuse.Results: The prevalence of co-occurring symptoms of ADHD and depression was 2.4% (boys 1.0%, girls 3.9%). The prevalence of experience of any sexual abuse was 20.9% (boys 13.3%, girls 28.7%). Of those with co-occurring symptoms, 48% of the boys and 47% of the girls reported a history of sexual abuse.Conclusions: School-based screening for co-occurring symptoms of ADHD and depression might be a method that identifies students at psychiatric and psychosocial risk.
|
|
| 6. |
- Isaksson, Johan, et al.
(författare)
-
Early psychosocial adversity and cortisol levels in children with attention-deficit/hyperactivity disorder
- 2013
-
Ingår i: European Child and Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 22:7, s. 425-432
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies suggest a different regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis) with lower diurnal cortisol levels, especially in the morning, in children with attention-deficit/hyperactivity disorder (ADHD) compared with controls. Since exposure to foetal and childhood psychosocial adversity has been associated with both ADHD and HPA-axis functioning, such exposures may explain these low cortisol levels in ADHD via early programming of the HPA-axis. Thus, our main aim was to retrospectively study foetal and early childhood exposures to psychosocial adversity in children with ADHD and to relate these exposures to cortisol levels. Saliva samples were collected during a regular weekday in children, 6-17 years old, with clinically confirmed ADHD (n = 197) and non-affected comparisons (n = 221) for radioimmunoassay analysis of cortisol. Parental rating scales were used for categorising subtypes of ADHD and degree of exposure to adversity. Children with ADHD had more reports of at least one rated foetal adversity (p = 0.041) and childhood adversity (p < 0.001) than comparisons. The association between low morning cortisol levels and ADHD-symptoms remained when analyses were adjusted for adversities, age, sex, sampling time and symptoms of oppositional defiant disorder. No relation was found between exposures to foetal/childhood adversity and cortisol levels except for a positive relation between childhood adversity and cortisol morning increase in children with ADHD. The hypothesis that early adversity may influence the HPA-axis, leading to lower cortisol levels in children with ADHD, was not supported by our findings.
|
|
| 7. |
- Hodgins, Sheilagh, et al.
(författare)
-
A 5-year follow-up study of adolescents who sought treatment for substance misuse in Sweden
- 2014
-
Ingår i: European Child and Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 23:5, s. 347-360
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that substance misuse in adolescence is associated with increased risks of hospitalizations for mental and physical disorders, convictions for crimes, poverty, and premature death from age 21 to 50. The present study examined 180 adolescent boys and girls who sought treatment for substance misuse in Sweden. The adolescents and their parents were assessed independently when the adolescents first contacted the clinic to diagnose mental disorders and collect information on maltreatment and antisocial behavior. Official criminal files were obtained. Five years later, 147 of the ex-clients again completed similar assessments. The objectives were (1) to document the prevalence of alcohol use disorders (AUD) and drug use disorders (DUD) in early adulthood; and (2) to identify family and individual factors measured in adolescence that predicted these disorders, after taking account of AUD and DUD in adolescence and treatment. Results showed that AUD, DUD, and AUD + DUD present in mid-adolescence were in most cases also present in early adulthood. Prediction models detected no positive effect of treatment in limiting persistence of these disorders. Thus, treatment-as-usual provided by the only psychiatric service for adolescents with substance misuse in a large urban center in Sweden failed to prevent the persistence of substance misuse. Despite extensive clinical assessments of the ex-clients and their parents, few factors assessed in mid-adolescence were associated with substance misuse disorders 5 years later. It may be that family and individual factors in early life promote the mental disorders that precede adolescent substance misuse.
|
|
| 8. |
- Isaksson, Johan, et al.
(författare)
-
Polymorphisms in the FK506 binding protein 5 gene are associated with attention deficit hyperactivity disorder and diurnal cortisol levels
- 2015
-
Ingår i: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 104:9, s. 910-915
-
Tidskriftsartikel (refereegranskat)abstract
- AimPrevious studies have shown an association between childhood attention deficit hyperactivity disorder (ADHD) and a down-regulated hypothalamus-pituitary-adrenal axis (HPA axis) with low diurnal cortisol levels. Given the role of the FK506 binding protein 5 (FKBP5) as an important regulator of the negative feedback system of the HPA axis, we set out to investigate possible associations between single nucleotide polymorphisms (SNPs) in FKBP5 in relation to ADHD and diurnal cortisol levels. MethodsChildren with ADHD (n=81) and healthy comparisons (n=88) collected saliva four times during a regular school day for radioimmunoassay analysis of cortisol and for genotyping of five SNPs in FKBP5 (rs9296158, rs1360780, rs9470080, rs7748266 and rs9394309). ResultsWe found associations between SNP genotypes and ADHD as well as between genotypes and diurnal cortisol levels. One of these SNPs, rs9470080, was significantly associated with both ADHD and lower cortisol levels. ConclusionThis study contributes to previous findings on a down-regulated HPA axis in children with ADHD by demonstrating an association between ADHD, lower cortisol levels and SNPs of the FKBP5-gene. The relevance of these findings for the development and shaping of ADHD symptoms needs to be approached in larger samples, preferably also taking stress reactivity into consideration.
|
|
| 9. |
- Isaksson, Johan, et al.
(författare)
-
The Pressure-Activation-Stress scale in relation to ADHD and cortisol
- 2015
-
Ingår i: European Child and Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 24:2, s. 153-161
-
Tidskriftsartikel (refereegranskat)abstract
- The Pressure-Activation-Stress (PAS) scale is a self-report questionnaire for children concerning perceived stress. To explore behavioral and physiological correlates, we investigated if scores discriminate between a group prone to perceive high levels of stress [children with attention-deficit/hyperactivity disorder (ADHD)] and a healthy school sample, and if they are associated with diurnal cortisol levels. The PAS scale was filled in at home by children (11-17 years) with clinically confirmed ADHD (n = 102) and non-affected comparisons (n = 146). Saliva samples were collected four times during a regular school day for radioimmunoassay analysis of cortisol. Subtypes and severity of ADHD symptoms were determined using parental rating scales. Children with ADHD scored higher on the PAS scale than a school sample. The PAS scores were similar over ages in the ADHD group while they increased with age in the healthy group. Female sex was associated with higher stress in both groups but no gender interaction was found. No association was found between PAS scores and cortisol levels in neither group. Children in the ADHD group had a lower ratio of cortisol levels/perceived stress on all sampling occasions, built up both by the higher PAS scores and the lower cortisol levels in children with ADHD. The higher PAS scores in children with ADHD support the validity of the scale. The lack of association between PAS scores and diurnal cortisol levels is intriguing and illustrates the complexity of the stress concept. Stress-related fragility seems to accompany ADHD during childhood.
|
|
| 10. |
- Åslund, Cecilia, et al.
(författare)
-
Shaming experiences and the association between adolescent depression and psychosocial risk factors
- 2007
-
Ingår i: European Child and Adolescent Psychiatry. - Uppsala Univ, Clin Res Ctr, Cent Hosp Vasteras, S-72189 Vasteras, Sweden. Karlstad Univ, Dept Social Sci, Karlstad, Sweden. Lillehammer Univ Coll, Fac Hlth & Social Studies, Lillehammer, Norway. : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 16:5, s. 298-304
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate whether psychosocial risk factors such as parental separation, parental unemployment and experiences of sexual abuse are associated with adolescent depression, and whether shaming experiences (defined as experiences of being degraded, or ridiculed by others) may account for such an association. Method A total of 5048 Swedish adolescents answered the Survey of Adolescent Life in Vestmanland 2004 (SALVe—2004) during classhours. The survey included questions about depressive symptoms, parental separation, parental unemployment and experiences of sexual abuse. Results The psychosocial risk factors studied were all associated with depression, but several of these associations became non-significant when a factor for shaming experiences was entered into the models. The explained variance for depression furthermore increased from approximately 4–7% to 17–20% when shame was included. Conclusion Shaming experiences may mediate part of the association between psychosocial risk factors and depression. These findings may have important implications for the understanding of psychotherapeutic treatment of the effects of risk factors in depressed patients.
|
|
