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Serotonin transporter and BDNF polymorphisms interact to predict trait worry.

ABSTRACT: Excessive worry is associated with a range of psychological disorders. While previous studies have examined genes associated with a range of different anxiety phenotypes, none have explored genes specifically associated with the general tendency to worry.The present study tested associations between trait worry and functional polymorphisms of three candidate genes: the serotonin transporter-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene, the Val66Met region of the brain-derived neurotrophic factor (BDNF) gene, and the Val158Met region of the catechol-O-methyltransferase (COMT) gene.A heterogeneous sample of adult participants (n=173) completed the Penn State Worry Questionnaire (PSWQ) and provided DNA samples for genotyping.Results revealed a significant interaction between 5-HTTLPR and BDNF genotypes predicting levels of worry. Specifically, there was a significant positive association between 5-HTTLPR short alleles and PSWQ scores, but only in BDNF met allele carriers. COMT genotype was not significantly associated levels of worry, nor did COMT interact with 5-HTTLPR or BDNF genotypes to predict PSWQ scores.These findings provide preliminary evidence about the putative genetic etiology of worrying. Key limitations of the present study and corresponding directions for future research on this topic are discussed.

SUBMITTER: Bredemeier K

PROVIDER: S-EPMC4156552 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Serotonin transporter and BDNF polymorphisms interact to predict trait worry.

Bredemeier Keith K Beevers Christopher G CG McGeary John E JE

Anxiety, stress, and coping 20140425 6

<h4>Background and objectives</h4>Excessive worry is associated with a range of psychological disorders. While previous studies have examined genes associated with a range of different anxiety phenotypes, none have explored genes specifically associated with the general tendency to worry.<h4>Design</h4>The present study tested associations between trait worry and functional polymorphisms of three candidate genes: the serotonin transporter-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene, ...[more]

PMID: 24679122

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Project description:BackgroundScientific enthusiasm about gene × environment interactions, spurred by the 5-HTTLPR (serotonin transporter-linked polymorphic region) × 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 × SLE interaction predicts preschool-onset depression (PO-MDD), the earliest validated form of depression.MethodsChildren (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.ResultsA 5-HTTLPR × 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.ConclusionsExtending 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 × environment interactions across development, environment, and outcome but should be interpreted cautiously given the small sample size.

Dataset Information

Serotonin transporter and BDNF polymorphisms interact to predict trait worry.

Publications

Serotonin transporter and BDNF polymorphisms interact to predict trait worry.

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