Faculty Bibliography

OBJECTIVE: The authors examined the relationships between clinical characteristics, cognitive functioning, and history of violent behavior and substance use among outpatients with schizophrenia. METHODS: Ninety-six patients with a diagnosis of schizophrenia or schizoaffective disorder completed a clinical and neuropsychiatric battery that included tests of general intelligence, executive and frontal lobe function, visual-motor processing, and motor function. Violent behavior was defined on the basis of arrest records. Self-reported violent behavior and substance use were recorded. The study participants were separated into three groups: history of violent arrest (N=34), nonviolent arrest (N=23), and no arrest (N=39). The three groups were compared for differences in demographic characteristics, clinical symptoms, and scores on neuropsychological tests. RESULTS: Fifty-seven (59 percent) of the 96 participants had a history of arrest. Persons who were arrested for nonviolent crimes had a significantly lower mean+/-SD number of arrests (3.39+/-3.7) than those arrested for violent crimes (9.24+/-8.9). No significant differences in neuropsychological test scores or clinical ratings were found between the three groups. The prevalence of substance use disorders was 65 percent, 57 percent, and 36 percent among patients with a history of violent, nonviolent, and no arrest, respectively. Only 47 percent of participants with a criminal history accurately reported this history, and 11 percent of participants with a history of drug-related arrests acknowledged previous substance use. CONCLUSIONS: Performance on neuropsychiatric tests does not distinguish stable outpatients with schizophrenia who have a history of violent behavior from those who do not have such a history. Two established predictors of violence, a history of arrests and substance abuse, are unreliable when assessed by self-report

Numerous clinical studies demonstrate that subanesthetic doses of dissociative anesthetics, which are noncompetitive antagonists at the NMDA receptor, replicate in normal subjects the cognitive impairments, negative symptoms, and brain functional abnormalities of schizophrenia. Postmortem and genetic studies have identified several abnormalities associated with schizophrenia that would interfere with the activation of the glycine modulatory site on the NMDA receptor. Placebo-controlled clinical trials with agents that directly or indirectly activate the glycine modulatory site consistently reduce negative symptoms and frequently improve cognition in patients with chronic schizophrenia who are receiving concurrent typical antipsychotics. Thus, there is convincing evidence that hypofunction of a subset of NMDA receptors may contribute to the symptomatic features of schizophrenia.

BACKGROUND: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps. METHODS: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon. RESULTS: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels. CONCLUSIONS: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure.

The prevalence of schizophrenia is about 1% worldwide. Individuals with schizophrenia are at increased risk for osteoporosis and fractures for several reasons, including poor diet, lack of exercise, cigarette smoking, and polydipsia. Some antipsychotic medications may further increase the risk of fractures by causing dizziness, orthostatic hypotension, and falls. Studies in women with hyperprolactinemia resulting from pituitary tumors have demonstrated high rates of osteoporosis believed to result from hypoestrogenism. Similarly, hyperprolactinemia in men results in hypogonadism and bone loss. Preliminary surveys have indicated that schizophrenia patients also may have elevated rates of osteoporosis and pathological fractures, possibly resulting in part from the long-term administration of antipsychotic agents that produce hyperprolactinemia and secondarily lower estrogen and testosterone levels. This potential complication of treatment with certain antipsychotic agents requires careful study and could represent a serious public health problem.

BACKGROUND: Patients with schizophrenia demonstrate poor verbal memory, ascribed to impaired prefrontal and hippocampal function. Healthy adults can increase recall accuracy following encoding interventions, such as item repetition and the formation of semantic associations. We examined the effects of these interventions on both memory performance and retrieval-related hippocampal activity in healthy adults and patients with schizophrenia. METHODS: Twelve patients with schizophrenia and twelve healthy control subjects participated. During study, subjects counted either the number of meanings or T-junctions in words seen only once or repeated four times. At test, O15-positron emission tomography scans were acquired while subjects completed word-stems with previously studied items. RESULTS: Control subjects recalled more words overall, but both groups demonstrated similar performance benefits following deeper encoding. Both item repetition and the use of a semantic encoding task were associated with memory retrieval-related hippocampal recruitment in control but not schizophrenic participants. Patients with schizophrenia demonstrated greater activation of prefrontal cortical areas during word retrieval. CONCLUSIONS: Despite a lack of hippocampal recruitment, patients with schizophrenia showed intact modulation of memory performance following both encoding interventions. Impaired hippocampal recruitment, in concert with greater prefrontal activation, may reflect a specific deficit in conscious recollection in schizophrenia

Processing of sensory information in the human brain progresses from primary areas, dedicated to a single sensory feature, to multimodal areas, which integrate many features across sensory modalities. For some of these processes hemispheric dominance has developed. Here we report the results of a passive viewing task using positron emission tomography. Subjects were scanned twice while staring at a stationary visual noise pattern. Normal subjects showed a significant reduction of regional cerebral blood flow (rCBF) in a distributed right hemisphere network of brain regions during the second visual task. Schizophrenic subjects, however, showed significant increases of right hemisphere rCBF during the second visual task and showed significant decreases only in the left hemisphere. These results are consistent with the notion of reversed hemispheric asymmetry during the processing of sensory information in schizophrenia.