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.

Related Articles

LINK: What is dementia?

LINK The Mental Health Information Centre

LINK Memory problems in the elderly

LINK Sleep disorders

LINK Panic disorders

LINK You are not crazy and you are not alone

LINK The low-down on OCD

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.

 

 

 

 

 

 

 

 

 

Related Articles

LINK: What is dementia?

LINK The Mental Health Information Centre

LINK Memory problems in the elderly

LINK Sleep disorders

LINK Panic disorders

LINK You are not crazy and you are not alone

LINK The low-down on OCD

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.

 

 

 

 

 

 

 

 

LINK: What is dementia?

LINK The Mental Health Information Centre

LINK Memory problems in the elderly

LINK Sleep disorders

LINK Panic disorders

LINK You are not crazy and you are not alone

LINK The low-down on OCD

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.

 

 

 

 

 

 

 

LINK The Mental Health Information Centre

LINK Memory problems in the elderly

LINK Sleep disorders

LINK Panic disorders

LINK You are not crazy and you are not alone

LINK The low-down on OCD

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.

 

 

 

 

 

 

LINK Memory problems in the elderly

LINK Sleep disorders

LINK Panic disorders

LINK You are not crazy and you are not alone

LINK The low-down on OCD

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.

 

 

 

 

 

LINK Sleep disorders

LINK Panic disorders

LINK You are not crazy and you are not alone

LINK The low-down on OCD

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.

 

 

 

 

LINK Panic disorders

LINK You are not crazy and you are not alone

LINK The low-down on OCD

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.

 

 

June 2003