Effects of stressful life events, maternal depression and 5-HTTLPR genotype on emotional symptoms in pre-adolescent children (original) (raw)
Related papers
Journal of Child Psychology and Psychiatry, 2014
Background: Scientific enthusiasm about gene 9 environment interactions, spurred by the 5-HTTLPR (serotonin transporter-linked polymorphic region) 9 SLEs (stressful life events) interaction predicting depression, have recently been tempered by sober realizations of small effects and meta-analyses reaching opposing conclusions. These mixed findings highlight the need for further research. Converging evidence suggests that the effects of 5-HTTLPR genotype may be neurodevelopmental in origin, but we are not aware of empirical studies that have investigated whether the 5-HTTLPR genotype 9 SLE interaction predicts preschool-onset depression (PO-MDD), the earliest validated form of depression. Methods: Children (n = 234) aged 3-5 were recruited for a longitudinal study designed to examine PO-MDD. In a comprehensive baseline assessment, the child's primary caregivers completed questionnaires and were interviewed about their child's behaviors, psychiatric symptoms, and exposure to SLEs. Results: A 5-HTTLPR 9 SLEs interaction emerged, such that children homozygous for the short allele were more susceptible to depression in the context of elevated SLE than long allele carriers. In contrast, at low SLE exposure, short allele homozygotes had fewer depressive symptoms. The data were best fit by a plasticity model with a substantial reduction in fit by diathesis-stress models. Conclusions: Extending studies in adult and adolescent populations, these data suggest that 5-HTTLPR genotype may provide plasticity to environmental influence, for better or worse. Specifically, children homozygous for the short allele were more susceptible to the depressogenic effects of SLEs but benefitted, in the form of reduced depressive symptoms, in the context of relatively benign environmental conditions (i.e. relatively low SLE exposure). These data highlight the importance of examining gene 9 environment interactions across development, environment, and outcome but should be interpreted cautiously given the small sample size. 5-HTTLPR, stress, childhood MDD 455 Key points
Psychological Medicine, 2009
Background. Previous work suggests that daily life stress-sensitivity may be an intermediary phenotype associated with both genetic risk for depression and developmental stress exposures. In the current analysis we hypothesized that genetic risk for depression and three environmental exposures over the course of development [prenatal stress, childhood adversity and adult negative life events (NLEs)] combine synergistically to produce the phenotype of stress-sensitivity.
Gene–environment interactions in psychopathology throughout early childhood
Psychiatric Genetics, 2015
Up to 20% of children and adolescents worldwide suffer from mental health problems. Epidemiological studies have shown that some of these problems are already present at an early age. The recognition that psychopathology is a result of an interaction between individual experiences and genetic characteristics has led to an increase in the number of studies using a gene-environment approach (G × E). However, to date, there has been no systematic review of G × E studies on psychopathology in the first 6 years of life. Following a literature search and a selection process, 14 studies were identified and most (n = 12) of the studies found at least one significant G × E effect. This review provides a systematic characterization of the published G × E studies, providing insights into the neurobiological and environmental determinants involved in the etiology of children's psychopathology.
Genetic moderation of environmental risk for depression and anxiety in adolescent girls
The British Journal of Psychiatry, 2001
Background There is huge individual variation in people's response to negative life events. Aims To test the hypothesis that genetic factors moderate susceptibility to the environmentally mediated risks associated with negative life events. Method The Virginia Twin Study of Adolescent Behavioral Development (VTSABD) was used to study the effects of independent life events (assessed from maternal interview) on depression/anxiety (assessed from child interview) in 184 same-gender female twin pairs, aged 14–17 years, measured on two occasions. Results There was no genetic effect on the independent negative life events studied. A significant gene–environment interaction was found using structural equation modelling. There was no effect of independent life events on adolescents' depression in the absence of parental emotional disorder, but a significant effect in its presence. Conclusions There is an environmentally mediated effect of life events on depression/anxiety. Genetic fa...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2009
Previous research examining gene-environment interaction (GxE) with regard to vulnerability to depression and anxiety has yielded conflicting results. The present study was designed to further investigate GxE between 5-HTTLPR and exposure to environmental adversity, using different phenotypic and genotypic characterizations as well as different types of adversity within a prospective study design. Data were available from an ongoing epidemiological cohort study following the outcome of early risk factors from birth to adulthood. At age 19 yr, 309 participants (142 males, 167 females) were characterized on measures of depression and anxiety through interview and questionnaire (DSM-IV diagnosis, Beck Depression Inventory, Harm Avoidance). Environmental adversity was assessed at birth (family adversity), and at age 19 yr (stressful life events). Bi- and tri-allelic 5-HTTLPR genotypes were obtained from genomic DNA. Results indicated that depression and anxiety in 19-yr-olds were strong...
American Journal of Psychiatry, 2015
Replication of scientific findings is a major challenge in biomedical research. In psychiatry, the identification of measured gene-environment interactions (G3E) has promoted a heated debate over the past decade, with controversial results about its influence on disorders such as major depression. The authors sought to replicate a 2003 study on G3E in youth depression in a large birth cohort from a diverse setting. Method: Using data from the 1993 Pelotas Birth Cohort Study, and adopting a design as similar as possible to that of the original study, the authors tested whether the relationship between childhood maltreatment and a subsequent depressive episode diagnosis was moderated by 5-HTTLPR genotype. Of 5,249 individuals assessed at birth and followed up to age 18, data on the evaluation for depressive episodes in early adulthood, on childhood maltreatment, and on genotype were available for 3,558 participants, of whom 2,392 remained after conservative screening for previous depressive symptoms. Associations were investigated with logistic regression analyses and controlling for potential confounders. Results: The results replicated important findings of the original study, this time in a sample of young adults from a middle-income country: there was a differential doseresponse relationship between childhood maltreatment and major depression according to 5-HTTLPR genotype. Conclusions: After following a research strategy as comparable as possible to that of the original study, the results corroborated the existence of a measured G3E, now in a large sample from a different sociocultural context. These findings provide further evidence that a genetic variant in the 5-HTTLPR moderates the link between childhood maltreatment and youth depression.
Epidemiology and psychiatric sciences, 2014
Aims. Many studies of various stress reactive phenotypes suggest that 5-HTTLPR short allele carriers (S-carriers) are characterised by the stable trait of negative affectivity that is converted to psychopathology only under conditions of stress. In this study, we examined the moderating role of the 5-HTTLPR on the relationship between two objective chronic risk factors, i.e. socioeconomic status (SES) and family structure, and internalising symptoms across adolescence. Methods. A multigroup path analysis was employed in a general adolescent population sample of a 5-year follow-up study. Results. Internalising problems were significantly more stable in the S-carriers. The focus on the main dimensions of internalising problems, i.e. anxiety and depression, revealed two different developmental patterns. In the S-carriers Anxiety problems seemed to be more stable and to predict a possible evolution towards the development of Depressive problems. In the long allele homozygotes (LL-subjec...
Psychological Medicine, 2009
Background: Adverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Likewise, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and the Brain-Derived Neurotrophic Factor (BDNF) seem to modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the GxE interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study is to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), BDNF gene (Val 66 Met polymorphism) and childhood adversity in accounting for adult depressive symptoms. Methods: A sample of 534 healthy individuals filled in self-report questionnaires of depressive symptomatology (SCL-90-R) and different types of childhood adversities (CTQ). The 5-HTTLPR polymorphism (5-HTT gene) and the Val66Met polymorphism (BDNF gene) were genotyped in the whole sample. Results: Total childhood adversity (B=0.27, p<0.001), childhood sexual abuse (B=0.17, p<0.001), childhood emotional abuse (B=0.27, p<0.001) and childhood emotional neglect (B=0.22, p<0.001) had an impact on adult depressive symptoms. Childhood sexual abuse had a greater impact on depressive symptoms in Met allele carriers of the BDNF gene than in the Val/Val group (F=5.87; p<0.0001), and in S carriers of the 5-HTTLPR polymorphism (5-HTT gene) (F= 5.80; p<0.0001).
2006
Previous research has demonstrated that a polymorphism in the serotonin transporter gene (5-HTTLPR) and adverse psychosocial circumstances interact to predict depression. The purpose of the present study was to explore the extent to which sex modulates these effects. Eighty-one boys and 119 girls (16-19 years old) were interviewed about psychosocial background variables and genotyped for the 5-HTT promoter polymorphism. There were two main results. First, boys and girls carrying the short 5-HTTLPR allele react to different kinds of environmental factors. Whereas males were affected by living in public housing rather than in own owned homes and by living with separated parents, females were affected by traumatic conflicts within the family. Second, the responses of males and females carrying the short 5-HTTLPR allele to environmental stress factors go in opposite directions. Thus, whereas females tend to develop depressive symptoms, males seem to be protected from depression. The results suggest that both the molecular and the psychosocial mechanisms underlying depression may differ between boys and girls.
2009
Background: Adverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Likewise, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and the Brain-Derived Neurotrophic Factor (BDNF) seem to modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the GxE interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study is to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), BDNF gene (Val 66 Met polymorphism) and childhood adversity in accounting for adult depressive symptoms. Methods: A sample of 534 healthy individuals filled in self-report questionnaires of depressive symptomatology (SCL-90-R) and different types of childhood adversities (CTQ). The 5-HTTLPR polymorphism (5-HTT gene) and the Val66Met polymorphism (BDNF gene) were genotyped in the whole sample. Results: Total childhood adversity (B=0.27, p<0.001), childhood sexual abuse (B=0.17, p<0.001), childhood emotional abuse (B=0.27, p<0.001) and childhood emotional neglect (B=0.22, p<0.001) had an impact on adult depressive symptoms. Childhood sexual abuse had a greater impact on depressive symptoms in Met allele carriers of the BDNF gene than in the Val/Val group (F=5.87; p<0.0001), and in S carriers of the 5-HTTLPR polymorphism (5-HTT gene) (F= 5.80; p<0.0001).