John M. Cleghorn

Increased frontal and reduced parietal glucose metabolism in acute untreated schizophrenia

Frontal and parietal lobe metabolism was measured by [18F] fluorodeoxyglucose positron emission tomography in 8 never-medicated DSM-III schizophrenic patients and in 10 control subjects. Patients were in a psychotic episode at the time of this scan. Seven of eight had been ill less than 2 years and had only mild neurocognitive impairment. Frontal lobe glucose metabolism was significantly greater in schizophrenic patients than in controls. This finding differs from that of hypofrontality reported in chronic patients previously treated with neuroleptics. Relative glucose metabolism in the interior parietal lobe was significantly lower in schizophrenic patients than in controls. The frontal/parietal ratios were significantly greater in patients than in controls.

Neuroleptic drug effects on cognitive function in schizophrenia

Neuropsychological test performance was compared in 37 neuroleptic treated DSM-III schizophrenic patients, 27 untreated schizophrenic patients, and 27 normal controls. Neuroleptic treated patients performed significantly less well than untreated patients at recalling a complex figure, at planning on a mazes test, and had poorer fine motor coordination. Controls and untreated patients performed equally well on these tests. The results were not altered in 16 neuroleptic treated patients who had been prescribed low doses of benztropine, nor 38 patients who reported prior substance abuse. Similar cognitive impairments are observed in Parkinsons disease and are associated with dopaminergic antagonist drugs in schizophrenics. Therefore, they do not comprise part of the Schizophrenic Deficit State. Two tests were better performed by controls than patients. Reaction time was slower and more variable in both treated and untreated patient groups than controls. The recall of paraphrased passages was significantly poorer in both patient groups than controls, a finding that is robust in subgroups matched for IQ. Neuroleptic treatment was associated with significantly better performance on this test.

The effects of exogenous melatonin on the total sleep time and daytime alertness of chronic insomniacs: A preliminary study

The effects of exogenous, supraphysiologic doses of melatonin on the total sleep time and daytime alertness of patients with chronic insomnia was examined in a double blind, single crossover study. Melatonin (75 mg per os) or identical placebo was administered at 10 PM daily to 13 insomniac patients for 14 consecutive days. A significant increase in the subjective assessment of total sleep time and daytime alertness was demonstrated with melatonin but not with placebo. However, 7 of the 13 patients reported that the active treatment had no significant effect on subjective feelings of well-being.

Three clinical syndromes of schizophrenia in untreated subjects: relation to brain glucose activity measured by position emission tomography (PET)☆

A number of studies of chronically ill, medicated patients have found that the clinical symptoms of schizophrenia segregate into three syndromes which can be labelled poverty, disorganization, and reality distortion. It has been previously found that each of these syndromes is associated with a specific pattern of perfusion (rCBF) in paralimbic and association cortex and in related subcortical nuclei. We replicated the symptom factors in 20 untreated subjects. Utilizing positron emission tomography with 18-F-fluorodeoxyglucose as a tracer for glucose metabolism, we reconstructed a map of the entire cortical activity from 16 to 20 tomographic slices. Each of the three syndromes was associated with a different pattern of regional glucose metabolism. Findings in common with previous studies were an association of poverty with left cortical metabolic activity in prefrontal and superior parietal areas, reality distortion with left temporal activity, and disorganization with left inferior parietal lobule. This is the first report of an association between regional metabolic activity and clinical syndromes in untreated patients, strengthening previous models of distributed neural networks in this disorder.

Sensitization and tolerance to apomorphine in men: Yawning, growth hormone, nausea, and hyperthermia

This study investigated whether the indices of dopaminergic function, yawning and growth hormone release induced by apomorphine, as well as the drug-induced nausea and hyperthermia, show sensitization or tolerance to repeated injections. Five normal volunteers received 12 injections of apomorphine hydrochloride (0.75 mg/70 kg) every 2 weeks. Yawning, as measured by the latency of onset and the time of peak activity, showed sensitization. The growth hormone response showed no change. Feelings of nausea and hyperthermia showed tolerance to repeated injections. These findings suggest that yawning may be a suitable index of dopaminergic function in studies of schizophrenia.

Apomorphine effects on brain metabolism in neuroleptic-naive schizophrenic patients

Since neuroleptic treatment produces a significant increase in striatal metabolism relative to cortical metabolism, we wished to determine whether the dopamine agonist apomorphine (APO) might have the opposite effect, and whether it would discriminate schizophrenic patients from healthy controls. Eleven neuroleptic-naive schizophrenic patients (diagnosed according to DSM-III) and eight normal subjects were compared with respect to cerebral accumulation of 18F-fluorodeoxyglucose measured by positron emission tomography following APO, 0.75 mg/70 kg (weight adjusted), or saline. Relative striatal glucose metabolism decreased significantly after APO in schizophrenic patients but not in control subjects. Post hoc analysis of data in 12 other regions revealed that relative superior temporal metabolism decreased very slightly, but significantly, in schizophrenic patients but not in control subjects after APO, and that the posterior frontal region increased in control subjects but not in the patient group.

Teaching Some Principles of Individual Psychodynamics through an Introductory Guide to Formulations

One objective of psychiatric education can be to help trainees describe and understand major concerns patients experience in their key relationships, inner conflict and sense of self. A precis of major concepts and principles in this area (usually known as psychodynamics) is presented without the metapsychological framework which makes some of the literature difficult to grasp. This is intended to make learning more efficient and to facilitate the formulation of hypotheses about the presence or absence of specific conflicts, and problems in key relationships. We do not propose that these hypotheses necessarily explain psychopathology but that they (a) supplement formal diagnosis; (b) enrich the clinical data base by providing hypotheses which are testable in part by clinical observation and which can be tested scientifically; (c) provide understanding crucial to psychotherapy.

Influence of renal clearance on peripheral homovanillic acid measurements in healthy subjects and schizophrenic patients

In order to investigate the effect of renal clearance on plasma homovanillic acid (HVA) concentrations, we examined plasma concentration and urinary excretion of HVA and creatinine per 4 h over 24 h in eight male schizophrenic patients and eight healthy male subjects. Renal clearances of HVA and of creatinine were determined per 4 h period. No significant differences were found between groups in the total 24 h excretion of either HVA or creatinine. Although differences between groups in plasma HVA concentrations and urinary HVA excretion per 4 h did not reach statistical significance, the renal clearance of HVA was significantly lower in the patient group than in the control group. There was no difference between groups in creatinine clearance. Diurnal changes were seen in the renal clearance of HVA and creatinine in both groups. Renal HVA clearance decreased from 23.00-07.00 h, with a coincident decrease in urinary HVA excretion and an increase in plasma HVA concentration. We provide evidence that renal clearance is an important determinant of plasma HVA concentration, and should be considered when interpreting plasma HVA data.

Dose-Response Profiles of Plasma Growth Hormone and Vasopressin After Clonidine Challenge in Man

The objective of the study was to determine dose-response relationships of growth hormone, vasopressin, blood pressure, heart rate, and behavioral responses to clonidine. Ten healthy male volunteers were tested with each of three doses of clonidine (0.7, 1.4, and 2.1 micrograms/kg) with at least 1 week between tests. All doses gave a significant growth hormone response with a peak at 50 min. The high dose gave a significantly higher response than either the medium dose or the low dose, which did not differ from each other. Within individual subjects, there was a consistency of response to the different doses; thus, three of the volunteers had responses of 5 ng/ml or higher to the low dose. Those three subjects had higher growth hormone peaks after the highest dose than did six other subjects. Vasopressin showed a drop following clonidine after the two higher doses. Systolic blood pressure dropped following clonidine, showing a significantly greater drop for the medium and high doses than for the low dose. Diastolic blood pressure also showed a drop, but responsiveness did not differ between doses. There was significant dryness of mouth produced by clonidine, but no difference between doses. There was a significant sedative effect following clonidine which was greater for the high dose than for the medium or low dose. The finding that some subjects had a growth hormone peak of 5 ng/ml or greater after the low dose supports the hypothesis that use of a low dose strategy may be useful in confirming supersensitivity in conditions where increased responsiveness is suspected. The lack of difference between blood pressure responses to the medium and high doses of clonidine--doses that have different effects on growth hormone--supports the hypothesis that differences in responsiveness of presynaptic and postsynaptic alpha 2-adrenergic receptors exist.

Substance abuse and schizophrenia: Effects on symptoms but not on neurocognitive function

The authors compare symptoms and neuropsychological test performance in DSM-III schizophrenic patients who reported prior substance abuse (N = 38) with those in patients who reported no such abuse (N = 25) to determine the impact of substance abuse on the psychopathology of schizophrenia. Positive and negative symptom scores were derived from the Schedule for Affective Disorders and Schizophrenia. Sixty neuropsychological measures drawn from commonly used tests of intelligence, memory, learning, fluency, and problem solving were calculated. Separate analyses were performed on patients in a psychotic episode who were free of neuroleptics (N = 27) and on those taking maintenance neuroleptics (N = 36). Among unmedicated patients, those who reported prior substance abuse had significantly higher thought disorder scores. Among neuroleptic-medicated patients, hallucination and delusion scores were significantly higher in the patients who reported prior substance abuse. The substance abuse followed withdrawal from social relations and preceded the onset of positive symptoms. None of the neuropsychological tests discriminated between abusers and nonabusers.