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Serotonin transporter gene, childhood emotional abuse and cognitive vulnerability to depression.

ABSTRACT: Meta-analyses evaluating the association between the serotonin transporter polymorphism (5-HTTLPR) with neuroticism and depression diagnosis as phenotypes have been inconclusive. We examined a gene-environment interaction on a cognitive vulnerability marker of depression, cognitive reactivity (CR) to sad mood. A total of 250 university students of European ancestry were genotyped for the 5-HTTLPR, including SNP rs25531, a polymorphism of the long allele. Association analysis was performed for neuroticism, CR and depression diagnosis (using a self-report measure). As an environmental pathogen, self-reported history of childhood emotional abuse was measured because of its strong relationship with depression. Participants with the homozygous low expressing genotype had high CR if they had experienced childhood emotional maltreatment but low CR if they did not have such experience. This interaction was strongest on the Rumination subscale of the CR measure. The interaction was not significant with neuroticism or depression diagnosis as outcome measures. Our results show that 5-HTTLPR is related to cognitive vulnerability to depression. Our findings provide evidence for a differential susceptibility genotype rather than a vulnerability genotype, possibly because of the relatively low levels of abuse in our sample. The selection of phenotype and environmental contributor is pivotal in investigating gene-environment interactions in psychiatric disorders.

SUBMITTER: Antypa N

PROVIDER: S-EPMC2936121 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Serotonin transporter gene, childhood emotional abuse and cognitive vulnerability to depression.

Antypa N N Van der Does A J W AJ

Genes, brain, and behavior 20100503 6

Meta-analyses evaluating the association between the serotonin transporter polymorphism (5-HTTLPR) with neuroticism and depression diagnosis as phenotypes have been inconclusive. We examined a gene-environment interaction on a cognitive vulnerability marker of depression, cognitive reactivity (CR) to sad mood. A total of 250 university students of European ancestry were genotyped for the 5-HTTLPR, including SNP rs25531, a polymorphism of the long allele. Association analysis was performed for ne ...[more]

PMID: 20455953

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Project description:Serotonergic system dysfunction has been implicated in posttraumatic stress disorder (PTSD). Genetic polymorphisms associated with serotonin signaling may predict differences in brain circuitry involved in emotion processing and deficits associated with PTSD. In healthy individuals, common functional polymorphisms in the serotonin transporter gene (SLC6A4) have been shown to modulate amygdala and prefrontal cortex (PFC) activity in response to salient emotional stimuli. Similar patterns of differential neural responses to emotional stimuli have been demonstrated in PTSD but genetic factors influencing these activations have yet to be examined.We investigated whether SLC6A4 promoter polymorphisms (5-HTTLPR, rs25531) and several downstream single nucleotide polymorphisms (SNPs) modulated activity of brain regions involved in the cognitive control of emotion in post-9/11 veterans with PTSD. We used functional MRI to examine neural activity in a PTSD group (n = 22) and a trauma-exposed control group (n = 20) in response to trauma-related images presented as task-irrelevant distractors during the active maintenance period of a delayed-response working memory task. Regions of interest were derived by contrasting activation for the most distracting and least distracting conditions across participants.In patients with PTSD, when compared to trauma-exposed controls, rs16965628 (associated with serotonin transporter gene expression) modulated task-related ventrolateral PFC activation and 5-HTTLPR tended to modulate left amygdala activation. Subsequent to combat-related trauma, these SLC6A4 polymorphisms may bias serotonin signaling and the neural circuitry mediating cognitive control of emotion in patients with PTSD.The SLC6A4 SNP rs16965628 and 5-HTTLPR are associated with a bias in neural responses to traumatic reminders and cognitive control of emotions in patients with PTSD. Functional MRI may help identify intermediate phenotypes and dimensions of PTSD that clarify the functional link between genes and disease phenotype, and also highlight features of PTSD that show more proximal influence of susceptibility genes compared to current clinical categorizations.

Dataset Information

Serotonin transporter gene, childhood emotional abuse and cognitive vulnerability to depression.

Publications

Serotonin transporter gene, childhood emotional abuse and cognitive vulnerability to depression.

Similar Datasets

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