Ronald D. Kaplan

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.

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.

Substantive and methodological issues in a rating of cognitive and psychological function in multiple sclerosis

There is a need for a practical, reliable, and valid rating scale for cognitive function in Multiple Sclerosis due to the high frequency of cognitive dysfunction and its consequences for patients and family. The process of rating cognitive function is examined from the point of view of the observer, the observed, and the examination and rating scales. It is concluded that observers can be trained to reduce bias and increase reliability. The patient may be a source of information through diaries, check lists, and interviews. Rating items must be based on the major cognitive deficit factors in multiple sclerosis. Standardized examination must be the basis for ratings. Rating items must be clear and closely tied to observable behaviour. A series of steps for a project to develop an acceptable international cognitive rating scale is proposed.

Seasonal variations in prolactin levels in Schizophrenia

As part of an ongoing longitudinal study of drug-free schizophrenic patients, we serially sampled resting early morning prolactin levels in 10 subjects. In a preliminary analysis, these levels were compared to those found in matched normal control subjects over a 4-year period. Both control and schizophrenic subjects showed a marked annual variation in prolactin levels. Six schizophrenic patients sampled in each quarter of the year showed a significant annual rhythm, with prolactin highest in the spring (March-May). In seven schizophrenic patients and nine controls sampled at two seasons in the year, prolactin was significantly higher in spring-summer (March-August) than in fall-winter (September-February), with no difference between patients and control subjects.

Longitudinal instability of hormone responses in schizophrenia

We have shown that SCZ patients show higher GH responses to APO than do normals but only on certain occasions when studied longitudinally. GH responses tend to be exaggerated at the time of relapse, and during remission may be blunted or exaggerated. Only patients who at some time demonstrate incoherent thinking and formed delusions, have exaggerated GH responses. Resting serum PRL varies in some patients much more than in normal controls and tends to decline to very low levels at the time of relapse. Several possible sources of variance remain to be controlled. However, it is tempting to infer that the instability of GH responses and resting PRL levels may signify instability in the regulation of these hormones by DA.