Elsevier

Biological Psychiatry

Volume 65, Issue 4, 15 February 2009, Pages 349-355
Biological Psychiatry

Research Report
Amygdala Function and 5-HTT Gene Variants in Adolescent Anxiety and Major Depressive Disorder

https://doi.org/10.1016/j.biopsych.2008.08.037Get rights and content

Background

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 LG allele carriers vs. LA allele homozygotes) and their interaction with diagnosis (healthy vs. patients) on amygdala responses to emotional faces.

Methods

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.

Results

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 LG allele showed stronger amygdala responses to fearful faces than healthy adolescents without these alleles. Second, patients with two copies of the LA allele exhibited greater amygdala responses to fearful faces relative to patients with S or LG 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.

Conclusions

S/LG alleles in healthy adolescents, as in healthy adults, predict enhanced amygdala activation to fearful faces. Contrary findings of increased activation in patients with LALA relative to the S or LG alleles require further exploration.

Section snippets

Participants

Thirty-one unmedicated adolescents with a current anxiety disorder, or major depressive disorder (MDD), or both and 33 psychiatrically healthy adolescents were recruited through community health practitioners and advertisements (Table 1). Data from 6 patients and 18 healthy adolescents have been presented previously (7, 29). Patients with anxiety or MDD were combined based on evidence implicating 5-HTT allelic variants in risk for both (11). Excluding MDD-only patients showed no overall change

Behavioral Data

Ratings and RT data during “how afraid” are presented in Figure 3. Data for three healthy participants were not recorded. Significant Face Emotion [F(3,171) = 33.69, p < .001] and Diagnosis [F(1,57) = 4.99, p < .05] effects emerged on ratings. Angry faces received highest ratings (2.38), followed by fearful (2.00), neutral (1.56), and happy (1.24) faces. Patients gave higher ratings to face emotions (2.02) relative to control subjects (1.59). Similar Face-Emotion effects characterized RTs [F

Discussion

Effects of 5-HTT gene variants on amygdala responses to emotional faces were studied in healthy and anxious/depressed adolescents during internal fear evaluation. A significant Genotype-by-Diagnosis-by-Face-Emotion interaction emerged on right amygdala activity, reflecting three key findings. First, in healthy adolescents, stronger amygdala responses to fearful faces characterized S/LG carriers, relative to LALA individuals. Second, this was opposite in patients in whom LALA individuals

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