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This Month in Archives of General Psychiatry
March 1998

This Month in Archives of General Psychiatry

Arch Gen Psychiatry. 1998;55(3):204. doi:10.1001/archpsyc.55.3.204

Cognitive impairment (dementia) is known to be very common among elderly schizophrenic patients, raising the question if these patients are more prone to develop Alzheimer disease (AD). Purohit et alArticle report a comprehensive clinicopathological study of 100 cases of elderly schizophrenic subjects. They found that although clinical dementia was extremely common among these patients, postmortem examination of the brain specimens revealed only a small percentage of cases with pathological changes of AD or other dementing neurodegenerative diseases. The dementia in elderly schizophrenic patients, therefore, must be related to some alternative mechanisms.

Changes in cell size can be indicative of pathological processes in the central nervous system. Rajkowska et alArticle compared neuronal and glial sizes in the prefrontal cortex from postmortem brains of schizophrenic, Huntington diseased, and normal subjects. In the brains from schizophrenic patients, large neurons, particularly those in layer III, were atrophied, indicating a selective vulnerability of the connnections between the prefrontal cortex and other cortical areas. The patterning of cell size change in Huntington disease differed from that in schizophrenia in exhibiting considerable neuronal loss and gliosis.

Some patients with schizophrenia exhibit a slow deterioration in their cognitive and functional abilities that extends into late life, suggesting a neurodegenerative process. Using sophisticated methods to identify and quantify common markers of neurodegeneration and other forms of neural injury in the cerebral cortex of elderly persons with schizophrenia, Arnold et alArticle found no increases in neuropathological markers compared with elderly control cases and no significant correlations between markers and clinical ratings obtained prior to death. Neurodegeneration does not appear to play a role in schizophrenia, even in the most ill and deteriorated individuals.

Both the size of brain structures and brain metabolism itself are often reduced in schizophrenia. One exception is the striatum—the dopamine-rich target of antipsychotic drugs—which is larger and more active in some patients. Hypothesizing that these changes are drug-induced, Shihabuddin et alArticle measured striatal size and metabolism in never medicated vs previously medicated patients; both were greater in the treated subgroup. Higher metabolism was linked to increased adverse effects. Future studies should determine whether atypical antipsychotic drugs achieve their therapeutic effects without increases in striatal size and metabolism, and whether absence of increases predicts a favorable adverse-effect profile.

There is strong evidence from human and animal studies that serotonin activity decreases in the fall and winter months. Exaggerated decreases in serotonin activity might contribute to the depressed mood, increased eating behavior, and increased sleep experienced by patients with seasonal affective disorder (SAD). Levitan et alArticle report that female SAD patients in the depressed state have altered hormonal and mood responses to the serotonergic drug m-chlorophenylpiperazine. This suggests that women with SAD have an abnormal decrease in central serotonin activity during their fall/winter depressive phase.

Depressive symptoms are a common feature of schizophrenia, complicate the course of recovery, and introduce a heightened risk of suicide. Tollefson et alArticle reported on an international sample of nearly 2000 patients with schizophrenia or related disorders. Over half had at least moderate depression. The novel antipsychotic agent, olanzapine, outperformed the standard neuroleptic, haloperidol, on a series of mood-related measures. These findings suggest that symptoms of depression within schizophrenia, including suicidal ideation, are treatment responsive.

The effect of depression on return-to-drinking among persons with alcohol dependence has been controversial. Greenfield et alArticle consecutively recruited individuals hospitalized for alcohol dependence and followed them monthly for 1 year after discharge from the hospital. They found that subjects with a diagnosis of major depression at the time of entry into alcohol treatment relapsed to drinking after hospital discharge sooner than those without major depression. There was no gender difference in this effect.

The rapid spread of human immunodeficiency virus in impaired populations challenges prevention specialists to develop behavior change interventions that can be tailored to the special needs of persons with cognitive and attentional limitations. Susser et alArticle report on a randomized clinical trial that demonstrates the effectiveness of a sexual risk reduction intervention for homeless men with severe mental illness. The experimental group showed a substantial reduction in risky sexual behaviors compared with a control group throughout the 18 months of follow-up.