Imaging Genetics Applications in Child Psychiatry

National Institute of Mental Health Intramural Research Program, Mood and Anxiety Disorders Program, Bethesda, MD 20892-2670, USA.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 7.26). 08/2010; 49(8):772-82. DOI: 10.1016/j.jaac.2009.12.022
Source: PubMed


To place imaging-genetics research in the context of child psychiatry.
A conceptual overview is provided, followed by discussion of specific research examples.
Imaging-genetics research is described linking brain function to two specific genes, for the serotonin-reuptake-transporter protein and a monoamine oxidase enzyme. Work is then described on phenotype selection in imaging genetics.
Child psychiatry applications of imaging genetics are only beginning to emerge. The approach holds promise for advancing understandings of pathophysiology and therapeutics.

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Available from: Daniel S Pine, Dec 16, 2013
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    • "In the last decade, technological advances in neuroimaging and molecular genetics have facilitated the implementation of imaging genetics, a new strategy that enables to identify the effects of susceptibility genes on the brain (Domschke and Dannlowski, 2010; Pine et al., 2010; Willeit and Praschak-Rieder, 2010). Notably, genetic susceptibility effects are mediated by molecular and cellular mechanisms, which in turn modulate behavioral phenotypes by affecting the structural and functional properties of neural circuits (Atmaca et al., 2011; Hesse et al., 2011; MacMaster, 2010; Wu et al., 2012). "
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    ABSTRACT: Obsessive-compulsive disorder (OCD) occurs in ∼1-3% of the general population, and its often rather early onset causes major disabilities in the everyday lives of patients. Although the heritability of OCD is between 35-65%, many linkage, association, and genome-wide association studies have failed to identify single genes that exhibit high effect sizes. Several neuroimaging studies have revealed structural and functional alterations mainly in cortico-striato-thalamic loops. However, there is also marked heterogeneity across studies. These inconsistencies in genetic and neuroimaging studies may be due to the heterogeneous and complex phenotypes of OCD. Under the consideration that genetic variants may also influence neuroimaging in OCD, researchers have started to combine both domains in the field of imaging genetics. Here, we conducted a systematic search of PubMed and Google Scholar literature for articles that address genetic imaging in OCD and related disorders (published through March 2014). We selected 8 publications that describe the combination of imaging genetics with OCD, and extended it with 43 publications of comorbid psychiatric disorders. The most promising findings of this systematic review point to the involvement of variants in genes involved in the serotonergic (HTTLPR, HTR2A), dopaminergic (COMT, DAT), and glutamatergic (SLC1A1, SAPAP) systems. However, the field of imaging genetics must be further explored, best through investigations that combine multimodal imaging techniques with genetic profiling, particularly profiling techniques that employ polygenetic approaches, with much larger sample sizes than have been used up to now.
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    • "Particular interest has arisen concerning the relationship between anxiety and variation in the serotonin transporter (SERT) gene (Bengel et al., 1999; Gonda et al., 2009; Lesch et al., 1996; Sen et al., 2004). Understanding the contribution of genotype to anxiety is important because genetics may moderate relationships between anxiety and its neurobiological correlates (e.g., Pine et al., 2010; Xu et al., 2006). Accordingly, SERT variants could also moderate the relation of anxiety with loss aversion, a relation which, in the future, could be captured at the neural level in follow-up studies using functional neuroimaging tools. "
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    ABSTRACT: Loss aversion, a well-documented behavioral phenomenon, characterizes decisions under risk in adult populations. As such, loss aversion may provide a reliable measure of risky behavior. Surprisingly, little is known about loss aversion in adolescents, a group who manifests risk-taking behavior, or in anxiety disorders, which are associated with risk-avoidance. Finally, loss aversion is expected to be modulated by genotype, particularly the serotonin transporter (SERT) gene variant, based on its role in anxiety and impulsivity. This genetic modulation may also differ between anxious and healthy adolescents, given their distinct propensities for risk taking. The present work examines the modulation of loss aversion, an index of risk-taking, and reaction-time to decision, an index of impulsivity, by the serotonin-transporter-gene-linked polymorphisms (5HTTLPR) in healthy and clinically anxious adolescents. Findings show that loss aversion (1) does manifest in adolescents, (2) does not differ between healthy and clinically anxious participants, and (3), when stratified by SERT genotype, identifies a subset of anxious adolescents who are high SERT-expressers, and show excessively low loss-aversion and high impulsivity. This last finding may serve as preliminary evidence for 5HTTLPR as a risk factor for the development of comorbid disorders associated with risk-taking and impulsivity in clinically anxious adolescents.
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