Genetics of Anxiety Disorders

Abstract

This chapter provides a broad overview of the state of current research in the genetics of the major anxiety disorders. In addition tosummarizing findings regarding the individual clinical syndromes, we present data supporting genetic hypotheses that explain their comorbidity with each other and with related phenotypessuch as anxious personality traits and depression. We conceptually divide the chapter into three main sections based upon methodology: (1) genetic epidemiology of adult and pediatric anxiety (twin and family studies), (2) human molecular genetics (linkage and association), and (3) animal genetic models. These approaches provide complimentary and concurring evidence supporting the genetic basis underlying anxiety disorders as well as preliminary insight into the genetic mechanisms involved in their expression.

A Genetically Informed Study of the Longitudinal Relation Between Irritability and Anxious/Depressed Symptoms

“…4,7,10,17 Most of the extant studies have linked irritability to adult emotional problems and outcomes, whereas the present study shows a similar effect across the age of normative pubertal transition. Thus, rather than simply viewing irritability as a byproduct or correlate of emotional problems, this study adds to accumulating evidence indicating that irritability is a risk factor for the onset of internalizing problems within childhood and into adulthood and that genetic factors play a role in this manifestation.…”

“…16–18 Pediatric anxiety disorders are associated with higher heritability estimates compared to adults and their genetic effects exhibit a dynamic course throughout development. 17 Genetically informed studies also indicate that anxiety and mood disorders are interrelated facets of a broader internalizing construct, as the anxiety disorders share genetic and environmental risk factors with each other and with related phenotypes like major depression. 15,18 Additionally, there is evidence that irritability shares genetic variation with depression symptoms.…”

The Shared Etiology of Attentional Control and Anxiety: An Adolescent Twin Study

“…In particular, molecular approaches would be useful. Although molecular genetic investigations of anxiety phenotypes have been ongoing (for a current review see Perez, Otowa, Roberson‐Nay, & Hettema, ), we know less about potential genetic risk factors for AC. Adolescence is clearly an important period for AC and anxiety, but extending these results longitudinally in both directions is also necessary for a more comprehensive developmental perspective.…”

Etiology, triggers and neurochemical circuits associated with unexpected, expected, and laboratory-induced panic attacks

“…Quantitative trait loci (QTL) analyses can then be utilized to identify associations between a specific phenotypic anxiety-associated behavior and a marker locus for sets of genes. These approaches have linked chromosome 1, 4, and 15 with increased anxiety-associated behaviors:chromosome 1 with exploration, chromosome 4 with locomotor activity, and chromosome 15 with avoidance [see review in (Perez et al, 2013)]. The disadvantage to this approach is that the anxiety traits will result from multiple genetic differences, rather than manipulating one specific gene such as a candidate gene associated with PAs and PD.…”