Effects of clozapine on plasma catecholamines and relation to treatment response in schizophrenia: a within-subject comparison with haloperidol.

We conducted a within-subject comparison of the effects of clozapine and haloperidol on plasma levels of neurotransmitters and metabolites, and related changes in specific plasma neurochemicals with clozapine response. The subjects were 14 inpatients with schizophrenia or schzoaffective disorder, who were refractory to haloperidol and at least one other typical antipsychotic medication. Subjects underwent, in the following order: a 6-week "fixed, flexible dose" haloperidol trial, followed by a 2-4 week medication-free phase, and a 6-week clozapine trial. Plasma levels of norepinephrine (NE), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), and objective clinical ratings of total, positive, negative, and depressive symptoms were obtained at the end of each phase. As expected, we found a substantial increase of plasma NE with clozapine but not with haloperidol. However, the increase in NE was not associated with improvement in total or positive symptomatology. There was some evidence for an association between improvement in negative symptoms and increased HVA on clozapine, as well as diminished HVA during the medication-free phase. The implications of these data for understanding the mechanisms of action of clozapine are discussed.

Developmental abnormalities and cortical sulcal enlargement in psychosis.

Neurodevelopmental abnormalities and cortical sulcal enlargement both occur in schizophrenia. To test the hypothesis that these abnormalities were related, CT scans from 164 psychotic patients (80 with schizophrenia) were reviewed. Neurodevelopmental abnormalities were observed in 11%. Abnormalities were equally prevalent in schizophrenia and other psychotic disorders. Cortical sulcal enlargement was observed in 39% of patients with schizophrenia, and was not associated with developmental abnormalities. Different mechanisms may contribute to distinct structural abnormalities.

Results of computerised tomography during first admission for psychosis.

A cohort of 168 psychotic patients underwent computerised tomography (CT) during their first admission. Cortical atrophy was present in 40% of patients. The frequency of atrophy increased with age, but did not differ between patients with schizophrenia, schizoaffective disorder, bipolar disorder or psychotic depression. Other CT findings of note were present in 6.6% of patients, and included four infarctions, three arachnoid cysts, and one each of venous angioma, colloid cyst, cavum vergae and post-traumatic changes. The frequency of CT findings other than atrophy was increased in the psychotic depression group. The findings support the proposal of the onset of psychosis being an indication for CT.

Current thoughts on diabetes patient education in New Jersey.

The DCCT study proved that the incidence of long-term complications of diabetes mellitus decreases with improvement of blood glucose control. The health care team management approach for patients with diabetes mellitus has been demonstrated to result in improved metabolic control.

BMY 14802, a sigma receptor ligand for the treatment of schizophrenia.

The theoretical role of sigma receptors in psychosis has led to the development of selective sigma receptor ligands as potential antipsychotic agents. BMY 14802 has its most potent binding at the sigma binding site, with some degree of serotonin subtype 1A and negligible dopamine receptor binding. It is atypical of standard neuroleptics in that it does not induce catalepsy in rats. It has been shown to have efficacy in animal models of psychosis. It was hypothesized that the drug would have antipsychotic effects in humans without producing the extrapyramidal side effects typical of standard neuroleptics. We report here the results of an uncontrolled, multicenter safety and efficacy study of patients with acute exacerbations of schizophrenia treated with BMY 14802. After 1 week of single-blind placebo treatment, 28 patients were treated with BMY 14802 (up to 3000 mg/day) for up to 4 weeks. There was no significant improvement in psychiatric symptoms, as measured by the total Brief Psychiatric Rating Scale scores or Clinical Global Improvement. There were no changes in involuntary movements, as measured by the Abnormal Involuntary Movement Scale, or in extrapyramidal symptoms as measured by the Simpson-Angus Scale.

Clinical presentations of AIDS and HIV infection in state psychiatric facilities.

The epidemiologic, neuropsychiatric, and medical data on AIDS and HIV infection that are relevant to state psychiatric facilities are reviewed. The epidemiologic data suggest that a larger than expected number of AIDS patients may be seen in these facilities. Patients who are severely disturbed and psychotic may present to state hospitals with HIV encephalopathy. In patients who are chronically and severely ill, physical symptoms, including oral and cutaneous conditions, the HIV wasting syndrome, and lymphadenopathy, may provide early clues to HIV infection. The early neuropsychiatric and medical findings in HIV infection are discussed, and a clinical case is presented.

Occult thyroid dysfunction in patients with refractory depression.

Assessment of metabolic rate was useful in evaluating refractory depression in six of 15 women. Five of the six had normal levels of T3 and T4; however, each had an elevated thyrotropin-stimulating hormone level or a low metabolic rate. The depressions responded to medication with thyroid hormone.

Ectopic production of big ACTH in carcinoma of the lung. Its clinical usefulness as a biologic marker.

This report considers the potential usefulness of adrenocorticotropic hormone (ACTH) determinations in diagnosis and in prognosis for therapy of patients with carcinoma of the lung but without clinical Cushing's syndrome. The report is based on radioimmunoassay data from 129 patients, including 62 with lung cancers and 67 with nonmalignant pulmonary conditions. Elevated plasma ACTH was found in 21 of 24 patients with untreated cancer and the hormone was detected in tumor extracts and/or bronchial washings from the remaining 3. Elevation of plasma ACTH was found in only 10 of 38 treated patients. Absence of clinical Cushing's syndrome in spite of high plasma ACTH concentrations is explained by the observation that the predominant form of ectopic ACTH in plasma is immunoreactive but nonbioactive 'big' ACTH. Prolonged survival, for longer than 19 months, was observed in only 5 patients: all patients with low plasma ACTH after resection of the lung tumor and 2 of 3 patients with low plasma ACTH without therapy. ACTH was found in all available malignant tissue, primary and metastatic, from the lung carcinoma group,but not in normal lung or in 5 tumors metastatic to the lung. Of the 39 patients diagnosed initially to have chronic obstructive pulmonary disease, 14 showed plasma ACTH elevation. However, 3 of these patients with the highest concentrations subsequently manifested carcinoma or carcinoma in situ.

Ectopic ACTH production in carcinoma of the lung.

Immunoreactive ACTH was found in almost all tissue extracts of lung carcinoma from patients without clinical evidence of Cushing's syndrome; i.e. 14 of 15 primary tumors, nine of nine metastatic lymph nodes, and four of four metastatic liver nodules contained immunoreactive ACTH. The incidence of ACTH in extracts of other tumor types was much lower. Comparable normal tissues contained no detectable ACTH. Immunoreactive growth hormone, parathyroid hormone, or gastrin was not found in the same carcinoma tissue. The predominant form of ACTH in the tumor extracts was big ACTH. In pituitary extracts little ACTH predominated.53% of 83 patients with lung carcinoma had afternoon plasma ACTH levels greater than 150 pg/ml; more than 90% of plasmas containing less than 150 pg/ml were obtained from patients who had received radiation therapy or chemotherapy. 31% of 45 patients with chronic obstructive pulmonary disease (COPD), 28% of 25 patients with other severe lung disease, and 6% of 33 controls had elevated values. Big ACTH predominated in the plasma of patients with lung carcinoma or COPD having elevated ACTH levels. Tissue from the lung of a smoking dog with atypical histologic changes contained immunoreactive ACTH, almost exclusively in the big form, while tissue from another smoking dog that was histologically normal contained no ACTH. Thus ACTH may be present even in precancerous lung lesions. These studies suggest that serial plasma ACTH levels may be of value in screening for, and/or management of, patients with carcinoma of the lung.