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Interactive effect of 5-HTTLPR and BDNF polymorphisms on amygdala intrinsic functional connectivity and anxiety.

ABSTRACT: The serotonin transporter (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) gene polymorphisms have been associated with risk for affective disorders and functional variability of the amygdala. We examined whether the two genotypes interactively influence intrinsic functional connectivity (FC) of the amygdala and whether FC mediates the genetic association with anxiety. Eighty genotyped healthy adults underwent resting state fMRI and completed the self-reported State-Trait Anxiety Inventory. Interactive genetic association with anxiety was observed such that effects of 5-HTTLPR depended on the BDNF Val66Met polymorphism (rs6265 variant), with higher anxiety scores in short and Met carriers compared to the other allelic groups. Voxel-wise FC with left and right amygdala seeds identified regions that were sensitive to variability in anxiety scores. A significant moderated mediation model demonstrated that the effect of 5-HTTLPR genotype on anxiety, moderated by BDNF Val66Met genotype, was fully mediated by FC between the left amygdala and the right dorsolateral prefrontal cortex, a cognitive control-related region, during a task-free state. FC was highest in carriers of the 5-HTTLPR short allele and BDNF Met allele. These findings establish intrinsic amygdala-prefrontal functional connectivity as a potential intermediate phenotype for anxiety, an important step toward identification of causal pathways for vulnerability to affective disorders.

SUBMITTER: Loewenstern J

PROVIDER: S-EPMC6699775 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Interactive effect of 5-HTTLPR and BDNF polymorphisms on amygdala intrinsic functional connectivity and anxiety.

Loewenstern Joshua J You Xiaozhen X Merchant Junaid J Gordon Evan M EM Stollstorff Melanie M Devaney Joseph J Vaidya Chandan J CJ

Psychiatry research. Neuroimaging 20190129

The serotonin transporter (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) gene polymorphisms have been associated with risk for affective disorders and functional variability of the amygdala. We examined whether the two genotypes interactively influence intrinsic functional connectivity (FC) of the amygdala and whether FC mediates the genetic association with anxiety. Eighty genotyped healthy adults underwent resting state fMRI and completed the self-reported State-Trait Anxiety Inventor ...[more]

PMID: 30711709

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Project description:BACKGROUND:Connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) is compromised in multiple psychiatric disorders, many of which emerge during adolescence. To identify to what extent the deviations in amygdala-vmPFC maturation contribute to the onset of psychiatric disorders, it is essential to characterize amygdala-vmPFC connectivity changes during typical development. METHODS:Using an accelerated cohort longitudinal design (1-3 time points, 10-25 years old, n = 246), we characterized developmental changes of the amygdala-vmPFC subregion functional and structural connectivity using resting-state functional magnetic resonance imaging and diffusion-weighted imaging. RESULTS:Functional connectivity between the centromedial amygdala and rostral anterior cingulate cortex (rACC), anterior vmPFC, and subgenual cingulate significantly decreased from late childhood to early adulthood in male and female subjects. Age-associated decreases were also observed between the basolateral amygdala and the rACC. Importantly, these findings were replicated in a separate cohort (10-22 years old, n = 327). Similarly, structural connectivity, as measured by quantitative anisotropy, significantly decreased with age in the same regions. Functional connectivity between the centromedial amygdala and the rACC was associated with structural connectivity in these same regions during early adulthood (22-25 years old). Finally, a novel time-varying coefficient analysis showed that increased centromedial amygdala-rACC functional connectivity was associated with greater anxiety and depression symptoms during early adulthood, while increased structural connectivity in centromedial amygdala-anterior vmPFC white matter was associated with greater anxiety/depression during late childhood. CONCLUSIONS:Specific developmental periods of functional and structural connectivity between the amygdala and the prefrontal systems may contribute to the emergence of anxiety and depressive symptoms and may play a critical role in the emergence of psychiatric disorders in adolescence.

Dataset Information

Interactive effect of 5-HTTLPR and BDNF polymorphisms on amygdala intrinsic functional connectivity and anxiety.

Publications

Interactive effect of 5-HTTLPR and BDNF polymorphisms on amygdala intrinsic functional connectivity and anxiety.

Similar Datasets

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