Does psychiatric molecular genetics need to account for the birth cohort effect?

Major psychiatric disorders including alcohol use disorder are considered multigenic and the smallness of effects of individual genes may be attributed to either complex biological mechanisms or geneenvironment interactions. The latter explanation is highlighted by the relatively fast changes in secular trends and in cohort effects on alcohol use disorder. Interactions of candidate gene variants with birth cohort have been found in the Estonian Children Personality Behaviour and Health Study, a longitudinal investigation from 1998 with a sample highly representative of birth cohorts within a region. Such interactions regarding initiation of alcohol use or alcohol use disorder have been revealed for e.g., 5-HTTLPR, VMAT1, OXR and NRG1, and suggest that rapid alterations in the socioeconomic environment promote changes in the genetic vulnerability to environmental risks factors such as alcohol

A systematic review and secondary data analysis of the interactions between the serotonin transporter 5-HTTLPR polymorphism and environmental and psychological factors in eating disorders

Objectives: to summarize and synthesize the growing gene x environment (GxE) research investigating the promoter region of the serotonin transporter gene (5-HTTLPR) in the eating disorders (ED) field, and overcome the common limitation of low sample size, by undertaking a systematic review followed by a secondary data meta-analysis of studies identified by the review. Method: a systematic review of articles using PsycINFO, PubMed, and EMBASE was undertaken to identify studies investigating the interaction between 5-HTTLPR and an environmental or psychological factor, with an ED-related outcome variable. Seven studies were identified by the systematic review, with complete data sets of five community (n = 1750, 64.5% female) and two clinical (n = 426,100% female) samples combined to perform four secondary-data analyses: 5-I-M1PR x Traumatic Life Events to predict ED status (n = 909), 5-HTTLPR x Sexual and Physical Abuse to predict bulimic symptoms (n = 1097), 5-HTTLPR x Depression to predict bulimic symptoms (n = 1256), and 5-HTTLPRx Impulsiveness to predict disordered eating (n = 1149). Results: under a multiplicative model, the low function (s) allele of 5-HTTLPR interacted with traumatic life events and experiencing both sexual and physical abuse (but not only one) to predict increased likelihood of an ED and bulimic symptoms, respectively. However, under an additive model there was also an interaction between sexual and physical abuse considered independently and 5-HTTLPR, and no interaction with traumatic life events. No other GxE interactions were significant. Conclusion: early promising results should be followed-up with continued cross-institutional collaboration in order to achieve the large sample sizes necessary for genetic research

A Systematic Review and Secondary Data Analysis of the Interactions between the Serotonin Transporter 5-HTTLPR Polymorphism and Environmental and Psychological Factors in Eating Disorders

Objectives: To summarize and synthesize the growing gene × environment (G × E) research investigating the promoter region of the serotonin transporter gene (5-HTTLPR) in the eating disorders (ED) field, and overcome the common limitation of low sample size, by undertaking a systematic review followed by a secondary data meta-analysis of studies identified by the review. Method: A systematic review of articles using PsycINFO, PubMed, and EMBASE was undertaken to identify studies investigating the interaction between 5-HTTLPR and an environmental or psychological factor, with an ED-related outcome variable. Seven studies were identified by the systematic review, with complete data sets of five community (n = 1,750, 64.5% female) and two clinical (n = 426, 100% female) samples combined to perform four secondary-data analyses: 5-HTTLPR × Traumatic Life Events to predict ED status (n = 909), 5-HTTLPR × Sexual and Physical Abuse to predict bulimic symptoms (n = 1,097), 5-HTTLPR × Depression to predict bulimic symptoms (n = 1,256), and 5-HTTLPR × Impulsiveness to predict disordered eating (n = 1,149). Results: Under a multiplicative model, the low function (s) allele of 5-HTTLPR interacted with traumatic life events and experiencing both sexual and physical abuse (but not only one) to predict increased likelihood of an ED and bulimic symptoms, respectively. However, under an additive model there was also an interaction between sexual and physical abuse considered independently and 5-HTTLPR, and no interaction with traumatic life events. No other G × E interactions were significant. Conclusion: Early promising results should be followed-up with continued cross-institutional collaboration in order to achieve the large sample sizes necessary for genetic research

The effect of serotonin transporter gene promoter polymorphism on adolescent and adult ADHD symptoms and educational attainment: A longitudinal study

AbstractIntroduction:The purpose of this longitudinal study was to investigate the relationship between the 5-HTTLPR genotype, symptoms of ADHD in adolescence and adulthood, and educational attainment in a population representative sample. Neuroticism, depressive symptoms and general mental abilities were controlled for as possible confounding factors.Methods:ADHD symptoms were reported at age 15 and 18 by teachers using the Hyperactivity Scale of af Klinteberg and SNAP-IV, and self-reported at age 25 using the ASRS. Data about education were reported at age 25.Results:At age 15, subjects with the l/l genotype had more concentration difficulties compared to s-allele carriers, and they also had more inattention symptoms according to SNAP-IV at age 18. These results were not altered by taking neuroticism or depressive symptoms into account. No 5-HTTLPR genotype effect on self-reported ADHD symptoms at age 25 was found. Inattention symptoms in adolescence were associated with lower education in young adulthood. The proportion of subjects with higher education at age 25 was significantly larger among s/s genotype compared to the l/l or s/l genotype.Conclusions:The l/l genotype of the 5-HTTLPR is associated with inattentive symptoms during adolescence in the general population, and increases the likelihood of inferior educational level in young adulthood.</jats:sec