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What role will genetics play in psychiatry?

There is more to biology than genetics.

The identification of genetic factors involved in causing psychiatric disorders like schizophrenia holds great promise. But as this information becomes available, psychiatrists also must continue to attend to what schizophrenia feels like to individual patients.

The molecular characterization of a disease like schizophrenia may become enormously helpful in guiding researchers to new treatments and in helping to distinguish disease subtypes. But there is more to biology than genetics. The human brain and the disorders that can affect it are too complex to be seen exclusively through the reductionist lens of genetic research. Psychiatric illness is not just a matter of abnormal genes and malfunctioning neurons. It is, more intrinsically, what is clinically observed: unhappy and often ill people who behave aberrantly.

There is a long history in psychiatry of not paying enough attention to the complex biology of disease states. But with the increasing use of genetics and brain imaging, we see a shift toward taking biology too seriously. A better way to understand psychiatric disorders and to diagnose and manage individual patients is to use information that comes from all relevant sources.

The physician must take into account the observable clinical phenomenon of a patient's psychiatric condition as well as her genome and brain states.

In the assessment of complex patients, it's important to have as balanced a view as possible. Their disorder depends in part on their genome, in part on their brain, in part on their environment, and in part on the larger social structure in which the patient lives.

There are at least two ways to understand and apply genetic information: to classify a psychiatric disorder, and to diagnose and potentially treat individual patients. Pharmacogenetic data may also be useful for developing and prescribing drugs. An especially promising use for genetics is to link a genetic variant to a neurobiologic state that helps provide a mechanistic explanation of what is going on in the brains of patients with schizophrenia.

An example of the role that sociocultural context plays in schizophrenia can be found in the diagnostic frequency of two forms of the disorder: catatonic schizophrenia, and hebephrenia (disorganized schizophrenia). Catatonic schizophrenia, marked by a fixed state, is diagnosed much more frequently among patients in developing countries than among patients in developed countries. In contrast, hebephrenia, characterized by severe personality disintegration, is diagnosed in patients in developed countries far more often than among patients in developing countries. There is no clear explanation for this disparity, but it suggests that symptoms judged as pathological in one setting may not be viewed the same way in another setting.

Psychiatrists and other physicians need to be able to make excellent choices for their patients based on both scientific evidence and an understanding of why the patient is seeking medical care. The scientific evidence alone, including genetic information and data obtained from brain scans informs the process. But this evidence also gives an incomplete picture of what is going on inside the patient.

DR. ROBERT is a bioethicist at the center for biology and science at Arizona State University, Tempe, and at the University of Arizona-Phoenix.

JASON SCOTT ROBERT, PH.D.

The earlier we identify risk, the better.

The identification and use of genetic markers to help understand the causes of psychiatric disorders and to help diagnose, assess, and treat patients are complements to the traditional tools of psychiatry. Patients deserve treatment that taps into all of the potentially important interventions available, including using knowledge about the genetic variations that contribute to their disease.

Certain psychiatric disorders, such as schizophrenia, bipolar disorder, and several others, have a strong familial component. Although most cases of schizophrenia appear to be sporadic, we have studied cases in which, for example, a couple has five children and all of them have schizophrenia.

Both of these situations are consistent with schizophrenia as well as other psychiatric disorders that have a genetic underpinning. But the expression of the disease also is strongly influenced by a variety of environmental factors and exposures.

Psychiatric disorders are complex syndromes, similar to disorders like diabetes and hypertension. Included in what we call schizophrenia is likely to be a large number of different diseases that have overlapping clinical presentations, but different causes and differences in detailed symptoms. And the array of causes is probably as varied as the range of clinical manifestations.

It's unlikely that single gene variations cause a psychiatric disorder. Instead, constellations of genetic influences work together--and along with environmental factors--to produce the clinical state we see in patients.

Research has become increasingly sophisticated in its search for genetic variations that are associated with the development of schizophrenia. By using large, case-control analyses and by studying close to a million genetic markers, we hope to identify several candidate genes even if they are involved in causing only some cases of schizophrenia. Some candidate genes are involved in serotonergic or dopaminergic transmission. These genes produce proteins such as dopamine-receptors, serotonin transporter proteins, and enzymes involved in neurotransmitter metabolism.

Other genes of interest in schizophrenia include those that code for cholinergic receptors, and others that code for proteins involved in oligodendrocyte growth.

The identification of the genetic etiologies of schizophrenia will help to reduce the disorder's social stigma. If research proves that certain gene variants make it more likely for a patient to develop schizophrenia, such a finding will highlight that the onset of psychiatric illness is beyond a patient's control.

The identification of gene variants that are linked to disease onset also holds the promise for the development of targeted interventions that may slow or prevent the disease from occurring. The earlier we can identify a patient's risk and start effective treatments, the better the prospect for reducing the disease's severity.

Genetic testing to identify patients at high risk for developing a disease like schizophrenia sounds speculative, but it may become a reality in perhaps the next 5-10 years, and possibly even sooner for some other psychiatric diseases, such as certain dementias and autism.

DR. PATO is professor and chairman of the department of psychiatry and behavioral sciences at the University of Southern California in Los Angeles.

CARLOS N. PATO, M.D.
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Title Annotation:POINT/COUNTERPOINT
Author:Robert, Jason Scott; Pato, Carlos N.
Publication:Clinical Psychiatry News
Date:Apr 1, 2008
Words:1028
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