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Structure of genetic and environmental risk factors for dimensional representations of DSM–IV anxiety disorders

  • Kristian Tambs (a1), Nikolai Czajkowsky (a2), Espen R⊘ysamb (a3), Michael C. Neale (a4), Ted Reichborn-Kjennerud (a5), Steven H. Aggen (a4), Jennifer R. Harris (a6), Ragnhild E. ⊘rstavik (a7) and Kenneth S. Kendler (a4)...
Abstract
Background

Twin data permit decomposition of comorbidity into genetically and environmentally derived correlations. No previous twin study includes all major forms of anxiety disorder.

Aims

To estimate the degree to which genetic and environmental risk factors are shared rather than unique to dimensionally scored panic disorder, generalised anxiety disorder, phobias, obsessive–compulsive disorder and post-traumatic stress disorder.

Method

Data obtained from 2801 young-adult Norwegian twins by means of the Composite International Diagnostic Interview were analysed with the Mx program.

Results

A multivariate common factor model fitted best. The latent liability to all anxiety disorders was substantially more heritable (54%) than the individual disorders (23% to 40%). Most of the genetic effect was common to the disorders. Genes contributed just over 50% to the covariance between liabilities.

Conclusions

The five anxiety disorders all share genetic and environmental risk factors. This has implications for the revision of the anxiety disorder section in DSM–V.

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Copyright
Corresponding author
Kristian Tambs, Department of Mental Health, Norwegian Institute of Public Health, Box 4404 Nydalen, 0403 Oslo 3, Norway. Email: kristian.tambs@fhi.no
Footnotes
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This study was supported by NIH grants MH-068643 (principal investigator K.S.K.) and MH-65322 (principal investigator M.C.N.). The twin programme of research at the Norwegian Institute of Public Health is supported by grants from the Norwegian Research Council, the Norwegian Foundation for Health and Rehabilitation, the Foundation of Borderline Research, and the European Commission under the programme Quality of Life and Management of the Living Resources of the Fifth Framework Programme (number QLG2-CT-2002-01254). Genotyping of the twins was performed at the Starr Genotyping Resource Centre at Rockefeller University.

Declaration of interest

None.

Footnotes
References
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Structure of genetic and environmental risk factors for dimensional representations of DSM–IV anxiety disorders

  • Kristian Tambs (a1), Nikolai Czajkowsky (a2), Espen R⊘ysamb (a3), Michael C. Neale (a4), Ted Reichborn-Kjennerud (a5), Steven H. Aggen (a4), Jennifer R. Harris (a6), Ragnhild E. ⊘rstavik (a7) and Kenneth S. Kendler (a4)...
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eLetters

Subthreshold symptoms: Can they be ignored?

Keertish N, Resident of Psychiatry
10 November 2009

Dear editor,

The findings in this study seem to support the spectrum concept of anxiety disorders in which the dimensional approach takes precedence over the categorical approach. However, I fail to understand why subthreshold symptoms were not considered in an otherwise well designed study. There isclear evidence that the subthreshold anxiety disorders are more prevalent than the full-syndrome disorders[1]. Also, co-morbidity with other disorders is well documented even in those with subthreshold anxiety disorders[2]. This raises the question as to whether subthreshold symptomsand co-morbid conditions can be ignored if we are to reach a proper conclusion. Potential treatment implications of such studies necessitates further research.

References:

1. Carter RM, Wittchen HU, Pfister H, Kessler RC. One-year prevalenceof subthreshold and threshold DSM-IV generalized anxiety disorder in a nationally representative sample. Depress Anxiety. 2001;13(2):78-88.

2. Lewinsohn PM, Shankman SA, Gau JM, Klein DN. The prevalence and co-morbidity of subthreshold psychiatric conditions. Psychol Med. 2004 May;34(4):613-22.
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Conflict of interest: None Declared

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Co �Morbidity Or False Co-Morbidity?

Devender Singh Yadav, Staff Grade Psychiatrist
22 October 2009

The findings by the authors highlight that there is a single common factor (genes contributing to 54% of the covariance between liabilities) rather than many factors with regards to the inheritance of anxiety disorder as a group. Could it be that we are seeing different expressions of the same disorder rather than different disorders i.e. dimensional expression of anxiety spectrum rather than categorical diagnosis of specific anxiety disorders (false co-morbidity?).

The authors in this study also state that they have only looked at anxiety disorders and not depressive disorders. Had they included depressive disorders, would they have found a single factor for inheritance of anxiety and depressive disorders? (Which might point towards false co-morbidity).

There appears to be significant co-morbidity between individual anxiety disorders and between anxiety disorders and depression, which this study also states. In clinical practice differentiation between these disorders is difficult at times (because of blurring of categorical boundaries and also there is expression of anxiety spectrum rather than any specific anxiety disorder).

The gene of major depression does not appear to be unique, overlapping with those for anxiety and neuroticism. [1]

Also the processes that underlie anxiety disorders are substantially heritable. For example, twin research indicates a significant genetic component to the habituation, acquisition and extinction of fear stimuli. [2]

An Icelandic study [3] of anxiety disorders found evidence of significant linkage (LOD score of 4.18 to chromosome 9q31 in a subgroup of 25 families where one proband was affected with panic disorder. Because most affected individuals did not have panic disorder, the authors comment that this finding may represent susceptibility to anxiety in general, rather than specifically to panic disorder, which is what the present study found.

In the podcast by the Royal College of Psychiatrists, dated 08/02/08, Raj Persaud talks to Prof.Gerald M Rosen about his editorial in the BJP wherein Prof Gerald comments on contemporary findings that suggests PTSD may lack specificity and also validity and that is may be a variant of anxiety or depression. He mentions that many a cases of normal human experiences are wrongly categorized as PTSD and that ‘criterion creep’ may be leading to what some writers call post embitterment disorder, a book by the same name. [4a &4b]

In one of the editorials published in the BJP, Olatunji and colleagues [5] argue that the underlying cognitive processes in hypochondriasis may be more consistent with anxiety disorders. Could these seemingly unrelated disorders be an extension of the above argument of false co morbidities? In DSM III, hypochondriasis was classified under the categorical umbrella of Neurosis. Will the above arguments by Olatunji persuade a change in the classification system in DSM V?

Also CBT and Antidepressants are effective in treating anxiety disorders, depressive disorders, and? hypochondriasis, which sustains the above argument for these disorders being inherited through a common pathway (polygenic, multifactorial causation), but expressed differently? [6]

Possibly the above arguments of false co-morbidities, if any, would only be resolved by further research, I suppose.

I have no conflict of interest.References:1. Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ. Generalized Anxiety Disorder in Women- A population based twin study. Archive General Psychiatry.1992; 49(4): 267-272.2. Corvin A, Gill M. Psychiatric genetics. Core Psychiatry by Wright P, Stern J, Phelan M. second edition. Elsevier Saunders; 2005: page 48.3. Thorgeirsson TE et al. Anxiety with panic disorder linked to chromosome 9q in Iceland. Am J Hum Genet 2003 May; 72(5): 1221-30

4a. Rosen GM, Spitzer RL, McHugh PR. Problems with the post-traumatic disorder and its future in DSM-V. The British Journal of Psychiatry 2008v.192, p.3-4.4b.Raj Persaud speaking to Prof.Rosen, Podcast broadcast on 08/02/08, Royal College of Psychiatry.

5. Olatunji BO, Deacon BJ, Abramowitz JS. Is hypochondriasis an anxiety disorder? The British Journal of Psychiatry 2009v.194, p.481-482.

6. Owen MJ, Cardno AG, O’Donovan MC. Psychiatric genetics: back to the future. Molecular Psychiatry. Jan 2000; 5(1): 22-31
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Conflict of interest: None Declared

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