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A random assignment, double-blind, placebo-controlled evaluation was used to compare the effectiveness of rapid parenteral injections of fluphenazine hydrochloride with that of oral doses of the same drug in 16 patients with acute psychotic illnesses. Doses of fluphenazine hydrochloride were much higher in the parenteral neuroleptization group than in the oral administration group during the acute phase, although oral doses were equivalent during the continuation phase. The rate of improvement was not different for the two groups, but the rate of extrapyramidal side effects was higher in the parenteral neuroleptization group. The results suggest that rapid parenteral neuroleptization for the acute treatment of psychosis offers more risks than benefits.

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A computed tomographic (CT) brain scan study was conducted in 24 young males treated and followed up for hyperactivity since childhood. Compared to 27 matched controls, adults with a history of hyperactivity had a significantly greater frequency of cerebral atrophy. No differences in cerebellar atrophy frequency or in lateral cerebral ventricle-to-brain ratio (VBR) were found. The possible associations of hyperactivity or perhaps stimulant drug treatment to atrophic brain changes are discussed.

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Despite the plethora of clinical drug trials in tardive dyskinesia, few consistent findings have emerged. One possible reason for this is that there have been no serious attempts to define the role of major neurotransmitter systems (dopamine, norepinephrine, acetylcholine, serotonin, GABA) in one specific population of tardive dyskinesia patients. This study reports a series of five controlled drug trials in a population of patients with persistent tardive dyskinesia; each drug probed one of four neurotransmitter systems. The intra- and interpatient responses are analyzed and the implications of the pharmacologic response profiles for the clinical management of tardive dyskinesia are discussed.

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Lateral cerebral ventricular enlargement is now known to occur in some schizophrenic patients. To determine whether ventriculomegaly in schizophrenia is a static vs progressive process, we conducted a follow-up computed tomographic brain scan study on 11 young male patients, three years after initial scans were obtained. No significant change was found in the mean ventricles-brain ratio of this small schizophrenic sample after three years. Four of 11 patients showed noticeable increases (greater than 50%) in individual ratio. Methodologic problems are discussed and the need for follow-up studies as a research strategy is emphasized.

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The width, length, and ventricle-to-brain area ratio (VBR) of the third ventricle were measured in 55 consecutive young male schizophrenic patients and 27 matched control subjects. No differences in third ventricular dimensions were found between the two groups. However, schizophrenic patients with cerebellar atrophy had a significantly greater mean third ventricular length. Correlations of third ventricular VBR with lateral ventricular VBR, but not with sulcal widening, were found. The possible existence of a subset of schizophrenic patients defined by cerebellar atrophy and third ventricular enlargement is discussed.

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Consecutively admitted manic males (n = 24) who consented to participate in a computed tomographic (CT) study of the brain were studied. Those with a ventricle-to-brain ratio (VBR) 2 standard deviations above the mean VBR of a matched control group comprised the large VBR group; the remainder comprised the small VBR group. A controlled comparison of a series of clinical variables was conducted between the larger and smaller VBR groups. There were no differences in age of onset, duration of illness, substance abuse, electroconvulsive therapy, abnormal electroencephalogram, delusions, hallucinations, suicidal attempts, irritable or grandiose affect, family history, cognitive test scores, or response to drug treatment. However, manic males with larger VBRs were found to have a significantly lower frequency of hospitalization than those in the smaller VBR group.

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Tardive dyskinesia is widely believed to be a state of relative hyperdopaminergic and hypocholinergic imbalance in the striatum of patients chronically treated with neuroleptics. However, not all patients with tardive dyskinesia respond to cholinergic drugs, which theoretically should restore the balance and improve the symptoms. We report a controlled, double-blind, crossover study of choline chloride in 11 patients with persistent tardive dyskinesia. Seven patients showed partial or minimal improvement, while two did not change and two deteriorated. The results are discussed in the light of other similar findings in the literature, and the implications for pharmacological subtypes of tardive dyskinesia using cholinergic probes are explored.

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Several reports in the literature suggest that schizophrenic patients are disproportionately born during the colder months compared to the general population. In this study, we report differences in the seasonality of birth between the subtypes of chronic schizophrenia, particularly when gender is considered. Cold months' births (December to March) are most likely in nonparanoid females and paranoid males. Possible reasons for these differences are discussed in light of genetic and environmental factors in schizophrenia.

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Fifty-five chronic schizophrenic males who consented to have a computed tomographic (CT) brain scan were divided into those with cerebral atrophy evidenced by sulcal widening (n = 22) and those with normal sulci (n = 33). The two groups were compared on several clinical variables obtained from medical records by psychiatrists who were unaware of the CT results. Schizophrenic men with sulcal enlargement were significantly less likely to show agitation as a clinical symptom during an acute relapse and had significantly worse cognitive test scores on admission to the hospital. The implications of these findings are compared to the literature on ventricular enlargement and their clinical applications are discussed.

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In a group of 55 chronic schizophrenic men aged 20-45 years, the mean ventricle to brain ratio (VBR) on computerized tomographic brain scan was significantly greater than in 27 matched control subjects. A clinical comparison was then conducted between the schizophrenic patients with VBRs above (N = 19) or below (N = 36) 2 SD from the control mean. No differences were found in age of onset, premorbid history, duration of illness, severity of illness, response to neuroleptic drug treatment, presence of positive or negative symptoms, substance abuse, or cognitive testing. However patients with VBRs greater than 2 SD above the mean were significantly older and had a significantly higher frequency of history of schizophrenia in a first-degree relative.

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As a followup to a post-mortem study of the brains of schizophrenic and control subjects where the corpus callosum was found to be significantly thicker anteriorly in early onset compared to late onset schizophrenia, histological sections of 18 schizophrenic, 7 manic-depressive, and 11 medical/surgical control subjects were prepared using a stain for glia and a stain for callosal fibers. A quantitative study of the concentration of glial cells and interhemispheric callosal fibers revealed no difference between groups. A neuropathologist unaware of the tissue origin rated the histological sections for gliosis. There was significantly more severe gliosis in the callosi of the late onset schizophrenics compared to early onset schizophrenics as well as the control group. These preliminary findings suggesting callosal pathology are discussed, and the need for further studies is stressed.

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Fifty-five schizophrenic, 24 manic and 27 control subjects, all males between 20-45 years of age, were examined for structural brain abnormalities with computerized tomography (CT) scans. Both manic and schizophrenic samples had significantly larger ventricles than the control group. Cerebral atrophy was more frequent in schizophrenia, while cerebellar atrophy was more frequent in mania. An association between increased ventricular size and cerebellar atrophy was found in mania but not in schizophrenia. Cerebral atrophy was not associated with ventricular enlargement in either disorder. Implications of these findings are discussed.

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Sensory-motor lateralization was studied prospectively in a consecutive sample of male chronic schizophrenic patients. The sample was divided into paranoid (N = 27) and nonparanoid (N = 53) subjects according to the Tsuang-Winokur criteria. Significantly more left handedness was found in the paranoid group, suggesting the left hemispheric dysfunction may be important in the etiology of paranoid schizophrenia.

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