Biological Psychiatry - Vol. 2

By Hugo D'Haenen; J.A. Den Boer et al. | Go to book overview

Neurogenetics of Anxiety Disorders

Ronit Weizman and Abraham Weizman


Family and twin studies show that distinct and/or common genetic factors may play a role in anxiety disorders, although the magnitude of the genetic effect in each of the anxiety disorders is as yet unclear. A genetic liability apparently underlies the phenotypic expression of some of them; however, like other mental disorders, anxiety disorders exhibit a complex inheritance. That is, their transmission most likely requires the interaction of several genes and environmental factors that may predispose individuals to the disorder but do not always lead to its full clinical expression. Anxiety disorders may share a common genetic background with depression, as evidenced by the frequent coexistence of depressive and anxiety symptoms and me response of the anxiety disorders to antidepressant agents. The advances in genetic molecular technology and genetic epidemiology may help researchers to identify the genes contributing to the predisposition to these disorders and to clarify the interaction between genetic and environmental factors. However, in addition to the common difficulties of the molecular genetics of complex diseases, namely, nonMendelian inheritance patterns, incomplete penetrance, possibility of phenocopies, genetic heterogeneity, and variable expressivity (Lander and Schork, 1994), the major problem in the neurogenetic study of anxiety disorders is the definition of the heritable phenotype (Tsuang, Faraone and Lyons, 1993; Smoller and Tsuang, 1998).


Family Studies

Family studies have consistently shown that panic disorder (PD), with or without agoraphobia, is a familial phenotype (Tsuang, Faraone and Lyons, 1993; Vieland et al., 1996). First-degree relatives of probands with PD show a 3- to 21-fold higher lifetime risk of the disorder than relatives of unaffected probands. Goldstein et al. (1997) found that the risks of PD in adult first-degree relatives of probands was 17-fold higher when the age of onset in the proband was 20 years or less, but only six-fold higher when onset was after age 20 years.

First-degree asymptomatic relatives of patients with PD have a tendency to be more reactive to the CO2 challenge test (Perna et al., 1996). Furthermore, Perna et al. (1996) showed that PD probands with CO2 hypersensitivity accounted for most of the familial loading. It seems that CO2 hypersensitivity may be due to a particular genetic dysfunction and individuate a genetically homogeneous subgroup of patients with PD (endophenotype).

Twin Studies

Twin and adoption studies serve as a powerful tool in genetic research. The comparison of concordance rates between monozygotic (MZ) and dizygotic (DZ) twins can help clinicians estimate heritability, which is an index of the contribution of genetic factors to vulnerability to a disorder.

An effect of genetic factors in PD was shown in an early study by Torgersen (1983) who found that PD and agoraphobia with panic attacks were five times as frequent in MZ than in samesex DZ twins. Ten years later, Kendler et al. (1993) assessed 2163 women from a population-based twin registry and noted only a modest familial aggregation of PD on multifactorial-threshold analysis, the best estimates of the heritability of liability ranged from 30% to 40%. In a subsequent study, this team examined the structure of the genetic and environmental risk factors for six major psychiatric disorders (phobia, generalized anxiety disorder, panic disorder, bulimia, major depression, and alcoholism) in an epidemiologic sample of 1030 female–female twin pairs with known zygosity (Kendler et al., 1995). The estimated heritability of PD was 44%. The twin concordancerate for PD was also studied by Bellodi et al. (1998) in a sample of 90 same-sex twin pairs. They found that the probandwise concordance rates for PD were significandy higher in the MZ man in the DZ pairs (67% vs 0%), as were the concordance rates for spontaneous panic attacks (71% vs 18%). For CO2-induced PD, me rates were 55.6% and 12.5%, respectively. These data suggest a relevant role of genetic factors in CO2-induced panic attacks. The marked differences indicate that the genetic relationship is complex and not simply additive.

Segregation Studies

Segregation analysis of pedigrees determines me mode of transmission of a disorder using mathematical methods. The inclusion of twin pairs or adoptive relatives enables quantification of the degree and nature of environmental effects. Pedigree analyses of PD have suggested that a single major locus contributes to the inheritance of the disorder, although the possibility of polygenic inheritance has not been completely ruled out. Pauls et al. (1980) analyzed 19 kindreds of PD patients and found mat the disorder is transmitted as a Mendelian autosomal dominant trait with an allele frequency of 0.014, age-dependent penetrance, and average age of onset 21.9 years. Crowe et al. (1983), in a preliminary genetic analysis, tested the single major locus and multifactorial polygenic transmission models, and was unable to exclude either one. The best-fitting single-locus model predicted a disorder gene with an allele frequency of 0.05 and a penetrance of 45.5% in women and 24.6% in men. Vieland et al. (1996) performed a simple segregation analysis in 126 families of probands


Notes for this page

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items

Items saved from this book

This book has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this book

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Cite this page

Cited page

Citations are available only to our active members.
Buy instant access to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25,

Cited page

Bookmark this page
Biological Psychiatry - Vol. 2
Table of contents

Table of contents



Text size Smaller Larger Reset View mode
Search within

Search within this book

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Full screen
/ 730

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Citations are available only to our active members.
    Buy instant access to cite pages or passages in MLA, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25,

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    Buy instant access to save your work.

    Already a member? Log in now.

    Author Advanced search


    An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.