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The influence of five monoamine genes on trajectories of depressive symptoms across adolescence and young adulthood.

ABSTRACT: The influence of five monoamine candidate genes on depressive symptom trajectories in adolescence and young adulthood were examined in the Add Health genetic sample. Results indicated that, for all respondents, carriers of the dopamine receptor D4 5-repeat allele were characterized by distinct depressive symptom trajectories across adolescence and early adulthood. Similarly, for males, individuals with the monoamine oxidase A 3.5-repeat allele exhibited unique depressive symptom trajectories. Specifically, the trajectories of those with the dopamine receptor D4 5-repeat allele were characterized by rising levels in the transition to adulthood, while their peers were experiencing a normative drop in depressive symptom frequency. Conversely, males with the monoamine oxidase A 3.5-repeat allele were shown to experience increased distress in late adolescence. An empirical method for examining a wide array of allelic combinations was employed, and false discovery rate methods were used to control the risk of false positives due to multiple testing. Special attention was given to thoroughly interrogate the robustness of the putative genetic effects. These results demonstrate the value of combining dynamic developmental perspectives with statistical genetic methods to optimize the search for genetic influences on psychopathology across the life course.

SUBMITTER: Adkins DE

PROVIDER: S-EPMC3515661 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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The influence of five monoamine genes on trajectories of depressive symptoms across adolescence and young adulthood.

Adkins Daniel E DE Daw Jonathan K JK McClay Joseph L JL van den Oord Edwin J C G EJ

Development and psychopathology 20120201 1

The influence of five monoamine candidate genes on depressive symptom trajectories in adolescence and young adulthood were examined in the Add Health genetic sample. Results indicated that, for all respondents, carriers of the dopamine receptor D4 5-repeat allele were characterized by distinct depressive symptom trajectories across adolescence and early adulthood. Similarly, for males, individuals with the monoamine oxidase A 3.5-repeat allele exhibited unique depressive symptom trajectories. Sp ...[more]

PMID: 22293009

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Project description:Importance:Less favorable trajectories of depressive mood from adolescence to early adulthood are associated with current and later psychopathology, impaired educational attainment, and social dysfunction, yet the genetic and environmental risk factors associated with these trajectories are not fully established. Examining what risk factors are associated with different trajectories of depressive mood could help identify the nature of depression symptoms and improve preventive interventions for those at most risk. Objective:To examine the differential associations of genetic and environmental risk factors with trajectories of depression symptoms among individuals observed from ages 10 to 24 years. Design, Setting, and Participants:In a longitudinal cohort study established in 1990 and currently ongoing (the Avon Longitudinal Study of Parents and Children [ALSPAC]), growth mixture modeling was used to identify trajectories of depression symptoms in 9394 individuals in the United Kingdom. Associations of different risk factors with these trajectories were then examined. Analysis was conducted between August 2018 and January 2019. Main Outcomes and Measures:Trajectories were composed from depression symptoms measured using the Short Mood and Feelings Questionnaire at 9 occasions from ages 10 to 24 years. Risk factors included sex, a polygenic risk score taken from a recent genome-wide association study of depression symptoms, maternal postnatal depression, partner cruelty to the offspring's mother when the child was aged 2 to 4 years, childhood anxiety at age 8 years, and being bullied at age 10 years. Results:Data on all risk factors, confounders, and the outcome were available for 3525 individuals, including 1771 (50.2%) who were female. Trajectories were assessed between the mean (SD) age of 10.7 (0.3) years and mean (SD) age of 23.8 (0.5) years. Overall, 5 distinct trajectories of depression symptoms were identified: (1) stable low (2506 individuals [71.1%]), (2) adolescent limited (325 individuals [9.2%]), (3) childhood limited (203 individuals [5.8%]), (4) early-adult onset (393 individuals [11.1%]), and (5) childhood persistent (98 individuals [2.8%]). Of all the associations of risk factors with trajectories, sex (odds ratio [OR], 6.45; 95% CI, 2.89-14.38), the polygenic risk score for depression symptoms (OR, 1.47; 95% CI, 1.10-1.96), and childhood anxiety (OR, 1.30; 95% CI, 1.16-1.45) showed the strongest association with the childhood-persistent trajectory of depression symptoms compared with the stable-low trajectory. Maternal postnatal depression (OR, 2.39; 95% CI, 1.41-4.07) had the strongest association with the early-adult-onset trajectory, while partner cruelty to mother (OR, 2.30; 95% CI, 1.36-3.90) had the strongest association with the adolescent-limited trajectory. Bullying (OR, 8.08; 95% CI, 4.92-13.26) showed the strongest association with the childhood-limited trajectory. Conclusions and Relevance:The least favorable trajectories of depression symptoms (childhood persistent and early-adult onset) were associated with both genetic and environmental risk factors, but the 2 trajectories of limited duration that had resolved by early adulthood (childhood limited and adolescent limited) were not associated with the polygenic risk score or maternal postnatal depression. Bullying was strongly associated with both the childhood-persistent and childhood-limited trajectories, suggesting that this risk factor may have a time-specific effect. These findings suggest that examining genetic and multiple time-specific environmental antecedents could help identify trajectories of varying onset and chronicity.

Project description:Mixed findings exist in studies comparing brain responses to reward in adolescents and adults. Here we examined the trajectories of brain response, functional connectivity and task-modulated network properties during reward processing with a large-sample longitudinal design. Participants from the IMAGEN study performed a Monetary Incentive Delay task during fMRI at timepoint 1 (T1; n = 1304, mean age=14.44 years old) and timepoint 2 (T2; n = 1241, mean age=19.09 years). The Alcohol Use Disorders Identification Test (AUDIT) was administrated at both T1 and T2 to assess a participant's alcohol use during the past year. Voxel-wise linear mixed effect models were used to compare whole brain response as well as functional connectivity of the ventral striatum (VS) during reward anticipation (large reward vs no-reward cue) between T1 and T2. In addition, task-modulated networks were constructed using generalized psychophysiological interaction analysis and summarized with graph theory metrics. To explore alcohol use in relation to development, participants with no/low alcohol use at T1 but increased alcohol use to hazardous use level at T2 (i.e., participants with AUDIT≤2 at T1 and ≥8 at T2) were compared against those with consistently low scores (i.e., participants with AUDIT≤2 at T1 and ≤7 at T2). Across the whole sample, lower brain response during reward anticipation was observed at T2 compared with T1 in bilateral caudate nucleus, VS, thalamus, midbrain, dorsal anterior cingulate as well as left precentral and postcentral gyrus. Conversely, greater response was observed bilaterally in the inferior and middle frontal gyrus and right precentral and postcentral gyrus at T2 (vs. T1). Increased functional connectivity with VS was found in frontal, temporal, parietal and occipital regions at T2. Graph theory metrics of the task-modulated network showed higher inter-regional connectivity and topological efficiency at T2. Interactive effects between time (T1 vs. T2) and alcohol use group (low vs. high) on the functional connectivity were observed between left middle temporal gyrus and right VS and the characteristic shortest path length of the task-modulated networks. Collectively, these results demonstrate the utility of the MID task as a probe of typical brain response and network properties during development and of differences in these features related to adolescent drinking, a reward-related behaviour associated with heightened risk for future negative health outcomes.

Dataset Information

The influence of five monoamine genes on trajectories of depressive symptoms across adolescence and young adulthood.

Publications

The influence of five monoamine genes on trajectories of depressive symptoms across adolescence and young adulthood.

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