Amygdala function and 5-HTT gene variants in adolescent anxiety and major depressive disorder.

Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.
Biological psychiatry (Impact Factor: 8.93). 11/2008; 65(4):349-55. DOI: 10.1016/j.biopsych.2008.08.037
Source: PubMed

ABSTRACT Associations between a functional polymorphism in the serotonin transporter gene and amygdala activation have been found in healthy, depressed, and anxious adults. This study explored these gene-brain associations in adolescents by examining predictive effects of serotonin transporter gene variants (S and L(G) allele carriers vs. L(A) allele homozygotes) and their interaction with diagnosis (healthy vs. patients) on amygdala responses to emotional faces.
Functional magnetic resonance data were collected from 33 healthy adolescents (mean age: 13.71, 55% female) and 31 medication-free adolescents with current anxiety or depressive disorders (or both; mean age: 13.58, 56% female) while viewing fearful, angry, happy, and neutral facial expressions under varying attention states.
A significant three-way genotype-by-diagnosis-by-face-emotion interaction characterized right amygdala activity while subjects monitored internal fear levels. This interaction was decomposed to map differential gene-brain associations in healthy and affected adolescents. First, consistent with healthy adult data, healthy adolescents with at least one copy of the S or L(G) allele showed stronger amygdala responses to fearful faces than healthy adolescents without these alleles. Second, patients with two copies of the L(A) allele exhibited greater amygdala responses to fearful faces relative to patients with S or L(G) alleles. Third, although weaker, genotype differences on amygdala responses in patients extended to happy faces. All effects were restricted to the fear-monitoring attention state.
S/L(G) alleles in healthy adolescents, as in healthy adults, predict enhanced amygdala activation to fearful faces. Contrary findings of increased activation in patients with L(A)L(A) relative to the S or L(G) alleles require further exploration.

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    ABSTRACT: Background Major depressive disorder (MDD) often begins during adolescence when the brain is still maturing. To better understand the neurobiological underpinnings of MDD early in development, this study examined brain function in response to emotional faces in adolescents with MDD and healthy (HC) adolescents using functional magnetic resonance imaging (fMRI). Method Thirty-two unmedicated adolescents with MDD and 23 healthy age- and gender-matched controls completed an fMRI task viewing happy and fearful faces. Fronto-limbic regions of interest (ROI; bilateral amygdala, insula, subgenual and rostral anterior cingulate cortices) and whole-brain analyses were conducted to examine between-group differences in brain function. Results ROI analyses revealed that patients had greater bilateral amygdala activity than HC in response to viewing fearful versus happy faces, which remained significant when controlling for comorbid anxiety. Whole-brain analyses revealed that adolescents with MDD had lower activation compared to HC in a right hemisphere cluster comprised of the insula, superior/middle temporal gyrus, and Heschl׳s gyrus when viewing fearful faces. Brain activity in the subgenual anterior cingulate cortex was inversely correlated with depression severity. Limitations Limitations include a cross-sectional design with a modest sample size and use of a limited range of emotional stimuli. Conclusions Results replicate previous studies that suggest emotion processing in adolescent MDD is associated with abnormalities within fronto-limbic brain regions. Findings implicate elevated amygdalar arousal to negative stimuli in adolescents with depression and provide new evidence for a deficit in functioning of the saliency network, which may be a future target for early intervention and MDD treatment.
    Journal of Affective Disorders 10/2014; 168:44–50. DOI:10.1016/j.jad.2014.06.037 · 3.71 Impact Factor
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    ABSTRACT: The role of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in anxiety disorder and anxiety-related traits is controversial. Besides this study, few studies have evaluated the triallelic genotype in adolescents. The aim of this study was to investigate whether anxiety disorders and anxiety-related traits are associated with 5-HTTLPR (biallelic and triallelic) in adolescents, integrating both case-control-based and family-based designs in a community sample. This is a cross-sectional community study of 504 individuals and their families: 225 adolescents (129 adolescents with anxiety disorder and 96 controls) and their biological families. We assessed psychiatric diagnosis using the Kiddie Schedule for Affective Disorders and Schizophrenia. The Temperament and Character Inventory and the Resnick Behavioral Inhibition Scale were used to evaluate harm avoidance and behavioral inhibition. DNA was extracted from saliva and genotyped, including biallelic and triallelic 5-HTTLPR classification, by PCR-RFLP followed by agarose gel electrophoresis. We were not able to find any associations between 5-HTTLPR and anxiety-related phenotypes in both case-control and trio analyses. Further investigation and meta-analytic studies are needed to better clarify the inconsistent results with regard to the association between 5-HTTLPR and anxiety-related phenotypes in adolescents.
    Psychiatric Genetics 05/2014; 24(4). DOI:10.1097/YPG.0000000000000035 · 2.27 Impact Factor


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Jun 3, 2014