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: 10.26). 11/2008; 65(4):349-55. DOI: 10.1016/j.biopsych.2008.08.037
Source: PubMed


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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    • "In addition to the putative role of BDNF and associated neu - roplasticity in affective responses to emotional faces , associations between common genetic variation in serotonin transporter genes and individual differences in visual scanning of emotional faces have also been observed [ e . g . , Battaglia et al . ( 2005 ) and Lau et al . ( 2009 ) ] . In particular , a common polymorphism in the 5 - HT promoter region , 5 - HTTLPR , involved in the transport of serotonin to the presynaptic neuron , has been identified as a reliable indicator of psychological maladjustment . This polymor - phism is represented by two variants , a short ( S ) allele and a long ( L ) allele , with"
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    • "There are few studies with adolescent samples (Becker et al., 2007; Lau et al., 2009), an important period for genes to 'get out of the skin' (Salum et al., 2012). Further, few studies have used a multiphenotypic approach beyond diagnosis, which may reveal more appropriate phenotypes for specific genes. "
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