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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    ABSTRACT: Previous studies have documented both neuroplasticity-related BDNF Val66Met and emotion regulation-related 5-HTTLPR polymorphisms as genetic variants that contribute to the processing of emotions from faces. More specifically, research has shown the BDNF Met allele and the 5-HTTLPR Short allele to be associated with mechanisms of negative affectivity that relate to susceptibility for psychopathology. We examined visual scanning pathways in response to angry, happy, and neutral faces in relation to BDNF Val66Met and 5-HTTLPR genotyping in 49 children aged 4–7 years. Analyses revealed that variations in the visual processing of facial expressions of anger interacted with BDNF Val66Met genotype, such that children who carried at least one low neuroplasticity Met allele exhibited a vigilance–avoidance pattern of visual scanning compared to homozygotes for the high neuroplasticity Val allele. In a separate investigation of eye gaze towards the eye versus mouth regions of neutral faces, we observed that short allele 5-HTTLPR carriers exhibited reduced looking at the eye region compared with those with the higher serotonin uptake Long allele. Together, these findings suggest that genetic mechanisms early in life may influence the establishment of patterns of visual scanning of environmental stressors, which in conjunction with other factors such as negative life events, may lead to psychological difficulties and disorders in the later adolescent and adult years.
    Frontiers in Behavioral Neuroscience 07/2015; 9. DOI:10.3389/fnbeh.2015.00175 · 3.27 Impact Factor
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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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    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 · 1.94 Impact Factor
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    • "Specifically , controls with the low-expressing genotype activated the amygdala more to emotional faces relative to controls with the high-expressing genotype. However, the pattern was the opposite for youths with depression: depressed youths with the high-expressing genotypes show greater amygdala activation than do depressed youths with the lowexpressing genotypes (Lau et al., 2009). "
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    ABSTRACT: The development of socioemotional functioning is a complex process that occurs over a protracted time period and requires coordinating affective, cognitive, and social faculties. At many points in development, the trajectory of socioemotional development can be deleteriously altered due to a combination of environmental insults and individual vulnerabilities. The result can be psychopathology. However, researchers are just beginning to understand the neural and genetic mechanisms involved in the development of healthy and disordered socioemotional functioning. We propose a translational developmental neuroscience framework to understand the transactional process that results in socioemotional functioning in both healthy and disordered populations. We then apply this framework to healthy socioemotional development, pediatric anxiety, pediatric depression, and autism spectrum disorder, selectively reviewing current literature in light of the framework. Finally, we examine ways that the framework can help to frame future directions of research on socioemotional development and translational implications for intervention.
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