Exploring the genetics of anxiety disorders
Christine Lochner, MHIC
Community surveys have shown that many of the anxiety disorders are amongst the
most common of the psychiatric disorders, and that they cause extensive
suffering and interference with work and social functioning. Anxiety disorders
account for one third of all costs of mental illness, and obsessive-compulsive
disorder (OCD) is the 10th most disabling of all medical disorders.
Researchers and clinicians have worked for decades to reduce the suffering of
those with these disabling disorders, and current treatments can alleviate
symptoms for many. Unfortunately though, some people do not respond
satisfactorily, and none of these treatments offer sustained relief. More
effective treatment depends on discovering the causes of these disorders.
Searching for the causes
Despite strong evidence for genetic susceptibility, no single or specific
gene has been unambiguously identified for anxiety disorders such as OCD, panic
or social anxiety disorder. Many researchers believe that this is due, in part,
to the critical role that the environment plays in modulating genetic
susceptibility in mental disorders.
Scientists say that genetic characterization of affected individuals may
offer insight into the molecular and biochemical subcategories of the disorder
that clinicians may not be able to discern. This may offer great promise for
advancing diagnosis and treatment of the mental disorders.
A project launched in South Africa, the "Genetics of Anxiety Disorders
Research Project" aims to identify factors contributing to the development
of anxiety disorders in the South African population. This research focuses
mainly on obsessive-compulsive and related disorders such as Tourette's
syndrome, trichotillomania and body dysmorphic disorder, panic and social
anxiety disorder. Their investigations focus primarily on the interplay between
genetic factors and environmental factors such as childhood trauma, brain
injuries and streptococcal infections.
Evaluating patients
The program has to date evaluated hundreds of partcipants with disorders such
as OCD, social anxiety and panic disorder. The evaluations include a detailed
structured interview (SCID-DSM-IV) conducted by trained researchers, as well as
various measurements of symptom severity and symptom impact on quality of life.
Associated disorders and behavioural patterns are measured with established and
newly developed scales, and also include computer-based cognitive testing.
DNA is also isolated from each individual's blood and tested for variants of
specific genes involved in brain metabolism.
In particular, the pedigrees of Afrikaner OCD sufferers have been actively
researched for the past two years in order to ascertain shared ancestry between
apparently unrelated sufferers. This will help the team to detect even those
genes that play only a minor role in the disease, by analysing the gene variants
of affected individuals in family-based subsets. These candidate genes can then
be tested in other ethnic groups as susceptibility factors for the development
of OCD.
Results
The project has taken off with several new findings about anxiety disorders.
The work has appeared in internationally peer-reviewed journals. One of the
studies showed that there was a significantly greater severity of childhood
trauma, and emotional neglect specifically for patients suffering from OCD and
trichotillomania (TTM). Although various factors may play a role in the etiology
(causality) of both OCD and TTM, this study is consistent with some evidence
from previous studies which suggests that childhood trauma may play a role in
the development of these disorders.
Another study suggested that gender may have a role to play in OCD. In
particular, it seems that a gene called MAO-A has a different distribution in
men and women with OCD.
A study looking at quality of life in the anxiety disorders compared OCD,
social anxiety disorder (SAD), and panic disorder (PD). According to this study
the extent of impairment due to OCD, PD or SAD appears to be similar across
quality of life scales. However, they did show that various domains are
differentially affected in each of the disorders. For example, OCD patients had
more impairment in family life and activities of daily living, SAD patients had
more impairment in social life and leisure activities, and PD patients were less
able to avoid the use of non-prescribed drugs.
Role players
These analyses are undertaken at the MRC Unit on Anxiety and Stress Disorders
as well as the US/MRC Centre for Molecular and Cellular Biology - mostly by
using a statistically specialized computer-based program (SPSS).
The pedigree / genealogical research process is managed by the Genealogical
Institute of South Africa (GISA, University of Stellenbosch), which houses an
extensive Afrikaner genealogical database.
Since January 2001, the MRC Unit on Anxiety and Stress Disorders have
collaborated with the OCD Association of South Africa (OCDSA) (a collaborative
process formalised as the OCD Research Consortium of SA) to facilitate
recruitment of and support for participants and their families throughout the
country.
This research project is funded by the National Alliance for Research on
Depression and Anxiety (NARSAD) in the United States of America. Some of the
researchers involved in this project are also supported by the Medical Research
Council (MRC) of South Africa, the National Research Foundation and the
Harry/Doris Crossley Foundation.
Getting the message across
The project has been very active in providing information to the lay public
as well as medical practitioners regarding anxiety and stress disorders in
general. Travelling across South Africa, the team have been able to
recruit hundreds of patients with OCD and/or related conditions, 61 with
panic disorder and 73 with SAD. Patients are kept in the loop with results from
the studies through a "Genetics of Anxiety Disorders Newsletter". The
newsletter is updated every 6 months and is also available on the Internet
www.mentalhealthsa.co.za.
More information
For more information on anxiety disorders, research participation or the
research protocol, please contact the coordinator, Christine Lochner, at 021 -
938 9179 or email: cl2@sun.ac.za.
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References
1. Greenberg, PE, Sisitsky, T, Kessler, RC et al. (1999). The economic burden of
anxiety
disorders in die 1990's. J Clin Psych, 60: 427 - 435.
2. Murray, C. J. L. & Lopez, A. D. (1996). Global burden of disease: A
comprehensive assessment of mortality and disability from diseases, injuries and
risk factors in 1990 and projected to 2020. World Health Organization, Harvard.
3. First, M. B., Spitzer, R. L., Gobbon, M., Williams, J. B. W. (1998)
Structured clinical
interview for DSM-IV Axis I disorders - Patient edition (SCID-I/P, Version 2.0,
8/98
revision). New York: New York State Psychiatric Institute, Biometrics Research
Department.
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