Laboratory of Neuro Imaging, Division of Brain Mapping,
UCLA School of Medicine, Los Angeles, CA
Invited Article for Psychiatric Times [to appear, March 2003]
[Download Article, 230 KB, .pdf]
[Figures: Click on the Image for Larger Version]
Schizophrenia is a devastating psychiatric disorder that affects 1% of the population worldwide. Patients often suffer their first psychotic outbreak in their late teens or early twenties. Despite advances in neuroleptic drugs, many patientsí symptoms remain refractory to treatment, with recurrent episodes of auditory and visual hallucinations, bizarre delusions, depression and social withdrawal that can last an entire lifetime. Neuroimaging studies now suggest that schizophrenia is a disorder of brain development, with anatomic abnormalities present at disease onset. Teenagers with a severe, early onset form of schizophrenia also exhibit a dynamically spreading wave of cortical gray matter loss, detectable in sequential MRI scans. The tissue loss begins in a small region of the parietal cortex and moves forward to engulf frontal and temporal systems. These deficits correlate with psychotic symptom severity, and may link with cortical dopamine or serotonin dysfunction. The shifting pattern of deficits is distinct from the neurodegeneration observed in the dementias, and may be an exaggeration or derailment of the neuronal remodeling that normally occurs in late teenage brain development. Computerized tracking of these cortical deficits will help understand how neuroleptic drugs decelerate or block the disease process. Cortical deficits are also detectable in patientsí first degree relatives, who are at greatly increased genetic risk for schizophrenia (10% lifetime risk). In future, these dynamic and genetic brain maps may predict imminent onset of the disease, identifying pre-symptomatic brain changes in family members who are candidates for early interventions.
Paul Thompson, Ph.D.
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