Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine.

According to the dopamine (DA) hypothesis of schizophrenia, there is a functional excess of dopaminergic activity within unspecified areas of the brain in schizophrenic patients. As a clinical test of this hypothesis, we administered metyrosine for three weeks to symptomatic chronic male schizophrenic patients who were maintained on suboptimal doses of neuroleptic agents. Metyrosine inhibits tyrosine hydroxylase, the rate-limiting enzymatic step in the synthesis of DA. No clinical improvement was observed, using the National Institute of Mental Health Inpatient Behavioral Rating Scale or the Brief Psychiatric Rating Scale. Central inhibition of DA synthesis by metyrosine was suggested, however, by (1) the development of extrapyramidal side effects and (2) a significant increase in plasma prolactin concentrations. Plasma chlorpromazine concentrations remained unchanged during metyrosine treatment. There was, nevertheless, a significant improvement on the scores of the Wechsler Adult Intelligence Scale Comprehension subtest, which measures judgment and common sense. This finding suggests that DA may be involved in the regulation of subtle psychological processes. The results are discussed in light of the DA hypothesis of schizophrenia and previous reports suggesting that metyrosine potentiates the antipsychotic effect of neuroleptics in schizophrenia.

Platelet MAO in subtypes of alcoholism.

A number of investigators have observed low platelet monoamine oxidase (MAO) activity in alcoholism. There is also preliminary evidence suggesting that low enzyme activity is principally associated with one of two putative subtypes of alcohol dependence, i.e., type II (male limited). The results of this study are consistent with two previous reports of reduced platelet MAO activity in type II male alcoholics as compared with type I male alcoholics and normal, healthy male controls. Type I (milieu-limited) alcoholics showed a smaller reduction in enzyme activity. The observed differences do not appear to be related to concurrent use of other psychoactive substances, characteristic differences in age between type I alcoholics and type II alcoholics, antisocial personality disorder, or variation in platelet size. Low platelet MAO activity in alcoholics is possibly related to both state and trait factors and may be a useful biochemical measure to assist with subtyping.

Cutaneous histamine response in schizophrenia.

A diminished cutaneous response to intradermal histamine has been reported by schizophrenics in at least 12 studies over the past 50 years. This literature is reviewed and compared to the present investigation in which both the wheal and flare response to intradermal histamine is examined in chronic schizophrenic patients, their parents, and a healthy control group. Histamine insensitivity could not be demonstrated in unmedicated patients, although a diminished wheal and flare response occurred during neuroleptic treatment. A cutaneous histamine insensitivity does not appear to be a common phenomenon among chronic schizophrenic patients.

Vocal activity in verbal hallucinations.

Vocal and forearm EMGs were recorded from 19 hallucinating and 22 nonhallucinating psychiatric inpatients. A microphone placed close to the lips was used to detect subvocal speech. The subjects' EMG and subvocal responses to pre-recorded statements were also assessed. Subjects who experienced hallucinations during assessment were asked to estimate the frequency of their hallucinations and rate phenomenological of their most recent hallucination. Results essentially replicated studies that found increased vocal potentials in hallucinators, but also showed that these increased potentials were nonsignificant when nonvocal measures are included in the statistical analysis. Subvocal speech and coincident increases in vocal EMG with reports of hallucinations, and with reports of pre-recorded statements, were not found. A significant negative correlation was found between the mean vocal potential of hallucinators and the perceived location of their most recent hallucination. The pre-recorded statements were generally perceived to be louder, clearer and more outside the head than the most recent hallucination.

A histological study of the corpus callosum in chronic schizophrenia.

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.

Effects of ECT given two vs. three times weekly.

The benefits and side effects of electroconvulsive therapy (ECT) given two vs. three times per week were examined in depressed inpatients. Twenty subjects were randomly assigned to one of two treatment conditions (unilateral ECT two or three times weekly). Examiners without knowledge of treatment condition rated depression and psychiatric status and administered tests of memory and visual-motor problem solving; subjects also provided self-ratings of depression. Measures were collected before treatment and 2 and 4 weeks after treatment began. Both schedules of treatment produced significant and equivalent improvements in psychiatric symptomatology, but visual memory impairment was significantly lower in the twice-weekly group.

Corpus callosum thickness in chronic schizophrenia.

In an effort at replication of the original report (Rosenthal and Bigelow, 1972) of increased callosal thickness in schizophrenic brains, the corpus callosum was measured in a blind study of 64 brains autopsied between the years 1972 and 1976. Diagnosis was established by independent chart review. The mean corpus callosum mid sections of 21 early onset chronic schizophrenic brains were found to have a significantly greater thickness when compared with 8 subjects with late onset schizophrenia, 13 patients with neurological diagnoses, or 14 patients with other psychiatric diagnoses. These studies, if independently confirmed, should provide an impetus for testing the hypothesis that some chronic schizophrenic patients have an illness associated with a pathological process in the corpus callosum.