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A Disorder of Neural Development? 

by Cindy Seiwert

Posted October 27, 2000 · Issue 89

Their teeth looked like fangs ready to devour me. Most of the time I couldn't trust myself to look at anyone for fear of being swallowed. I had no respite from the illness. Even when I tried to sleep, the demons would keep me awake. . . .

                                 - Janice Jordan
                                 Schizophrenia: Adrift in an Anchorless Reality

Schizophrenia is the most serious of the mental illnesses - affecting roughly one percent of the population worldwide - and it is, perhaps, the most feared. There are a number of excellent introductions to the topic. For example, you can visit the Web page Schizophrenia from the National Institute of Mental Health.
Many factors, from genes to fetal environment, trigger this disease.
Although schizophrenics do not have "split personalities" as is often assumed, they do experience a split between their realities and those of healthy people. Hallmark symptoms include hallucinations, delusions, disorganized speech and behavior, reduction of emotional range, and a variety of cognitive dysfunctions. Complete descriptions of this disease's symptoms can be found in Schizophrenia Overview, Mental Health: A Report of the Surgeon General, and at Facts on Schizophrenia from the National Alliance for the Mentally Ill. Moreover, the U.S. diagnostic criteria can be found at the National Alliance for Research on Schizophrenia and Depression's Schizophrenia site.

Because many loci have been associated with this disease, multiple genetic "hits" appear necessary to result in a predisposition to schizophrenia. Although no single gene confers susceptibility, genes are clearly involved. People with a first-order relative with the disease face a much higher risk - as high as 50 percent for monozygotic twins - than the general population. The genetic risk is reviewed in the Schizophrenia section of Genetics and Mental Disorders. Prenatal risk factors include: maternal obesity prior to pregnancy, influenza during second trimester, and obstetrical complications resulting in hypoxia. Citations for recent research on these topics can be found at Prenatal Problems Linked to Schizophrenia.

Like other mental illnesses, schizophrenia's symptoms reflect an underlying brain disorder. The anatomy and chemistry of the brains of schizophrenics differ markedly both from healthy individuals and from those with other psychiatric disorders. For instance, the brains of schizophrenics are smaller and have abnormal dopamine function, increased ventricular size, unusual laterality of the cortex, and more subtle differences.
The brain glitch arises early in development.
Just what causes this neural pathology is unknown, as is how altered brain structure translates into schizophrenic symptoms. Recently, a new vision of schizophrenia and its etiology came up, one that considers schizophrenia as a unitary, if not strictly localized, entity. In's Brain Work, Nancy Andreasen wrote, "These newer models localize the symptoms of schizophrenia in distributed circuits, not in single regions. A disruption at the level of circuits may lead to an impairment in basic cognitive processes, such as good mental coordination of ideas or the ability to use abstract concepts to guide behavior." These basic disturbances then result in symptoms, which may vary between individuals depending on what part of the circuit is most severely disrupted. The disordered circuit is thought to include the prefrontal cortex, the thalamus, elements of the limbic system, and perhaps the cerebellum.

Recent theories do concur in that they are all developmental models that locate the primary lesion to the brain very early in development. The underlying neural pathology is thought to remain relatively dormant until the final maturation of the brain, which occurs during adolescence. For a thorough review of this, see The Neurodevelopmental Hypothesis of Schizophrenia. Much evidence supports this hypothesis. The brains of schizophrenics exhibit unusual folding of the cortex, a process that occurs in utero. Large residues of subplate cells, which normally disappear during development, are found in the brains of some schizophrenics. These cells help guide migrating neurons to their destinations, so their continued presence in adults suggests a mechanism for how the brains of schizophrenics become "mis-wired."
Related symptoms appear in childhood.
The existence of prenatal/perinatal risk factors also supports developmental models. A number of prospective studies revealed that those who become schizophrenic appear different early in life. As children, they experience speech problems, deficiencies in perceptual and motor skills, preference for solitary play, social anxiety, and slightly lower IQs, indicating that neurological differences exist long before the disease becomes manifest. Indeed, magnetic resonance imaging of the brains in people at high risk of developing schizophrenia suggests that abnormalities in brain structure precede the appearance of symptoms.

The acceptance of schizophrenia as a brain-based biological disorder, one that alters consciousness, is quite a change from 50 years ago, when researchers thought children were driven mad by their "schizophrenogenic" mothers. Now, we see schizophrenia as analogous to cancer in many ways - as a complex disease with many interacting etiological factors, one that requires the occurrence of many unfortunate events. With this understanding comes hope for better treatments and for effective intervention in the earliest parts of the disease process.

Cindy Seiwert is a freelance science writer based in Haddam, Connecticut. 
Frederick H. Carlson is a professional artist and illustrator whose clients include The Saturday Evening Post, Baltimore Sun and Pittsburgh Magazine.




What Is Schizophrenia? - home page of the Schizophrenia Society of Canada. Includes links to news, a discussion forum, and regional groups.

APA Online - home page of the American Psychiatric Association. Supplies news, clinical and research resources, a job bank, and public policy statements.

Schizophrenia - a broad collection of links. Provides information on diagnosis, treatment, and clinical trials, plus links to professional and advocacy organizations.

Schizophrenia - general information from the National Institute of Mental Health. Includes press releases, editorials, congressional testimony, and various publications.

Schizophrenia - links to current clinical trials relevant to this disease.

Schizophrenia Research Topics - a comprehensive site for searching the scientific research on schizophrenia, from Internet Mental Health. Covers subjects from behavioral therapy to virology.

Web sites mentioned in this article:

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