M.E. Kelley

Relations between cognitive and symptom profile heterogeneity in schizophrenia.

Although numerous studies have consistently revealed cognitive heterogeneity in schizophrenia, the relationships between such heterogeneity and clinical phenomenology are not clear. Clusters derived from cognitive heterogeneity studies may or may not be associated with symptom profile or severity of illness. The purpose of this study was to examine the relationship between cognitive heterogeneity and demographic and clinical phenomenological measures. We examined cognitive heterogeneity in schizophrenia by empirically deriving clusters of patients based upon WAIS-R subtest scores and then analyzed the way in which these clusters related to demographic and symptom variables and to DSM-III-R diagnostic subtypes. Four cognitive clusters were identified that were consistent with previous research. These clusters were differentiated on the basis of educational level and occupational status but not on the basis of symptom profile, severity, or DSM-III-R subtypes. Results suggest that cognitive measures are independent of severity of the disorder and phenomenological symptom presentation in these subgroups of schizophrenic patients.

Relationship between immune and behavioral measures in schizophrenia

Schizophrenia, which is a chronic but episodic disorder of unknown etiology, shares immunological features with organ specific autoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis and insulin-dependent diabetes mellitus. However, recent studies have raised the issue as to whether the reported immune disturbances in schizophrenia may be the result of a stress-induced dysregulation of CNS cytokine production, rather than a permanent immunological disorder, i.e., autoimmunity.

Dopamine turnover in schizophrenia before and after haloperidol withdrawal : CSF, plasma, and urine studies

The dopamine hypotheses of schizophrenia and antipsychotic drug action suggest that the dopamine metabolite homovanillic acid (HVA) should change with drug withdrawal and change in clinical state. We designed a study of cerebrospinal fluid (CSF), plasma, and urinary HVA on and off haloperidol to examine the effects of drug withdrawal. CSF and plasma HVA samples were obtained in 72 healthy schizophrenic (DSM-III-R) males (age: 36 ± 7.4 years), before and after haloperidol withdrawal, which was after 6 weeks on placebo or sooner if they met specific criteria for relapse. We collected three 24-hour urine samples in 34 of these patients. In addition, CSF HVA was obtained in 24 well-screened age-matched male normal controls. HVA was measured with high-pressure liquid chromatography (HPLC). CSF HVA decreased significantly after drug withdrawal, particularly in those who met relapse criteria; drug-free CSF HVA levels were not significantly different from those of normals. Plasma HVA increased significantly after haloperidol withdrawal in relapsing patients, but not in clinically stable patients. Urinary HVA excretion decreased after withdrawal with decreased HVA clearance. We conclude that haloperidol withdrawal had a strong effect on dopamine turnover, whereas the patient’s clinical state had only a weak central effect, without affecting total body production of HVA. Conceivably, dopamine involvement in schizophrenia reflects the failure of the homeostatic mechanisms that allow for integration of different functional brain components as needed.

Methodological concerns in the study of the immune system in schizophrenia

Background. Studies of immune measures in schizophrenia have shown differences with control subjects on a number of measures. However, immune measures are often not detectable in the serum or CSF of human samples and in many studies it is not clear how this was dealt with in the analysis. Methods. CSF IL-6 was measured by ELIS A in 6l drug free male schizophrenic (DSM-IIIR) patients and 25 well-screened healthy male control subjects. Serum IL-6 was measured in 43 of the 61 patients, and in 16 control subjects. Data were analyzed with and without non-detectable values to determine if this affected the results. Results. Using a value of “0” for non-detectable values resulted in significant differences between patients and controls in plasma interleukin-6. However, if these values were treated as missing, the difference was not significant. Conclusions. The treatment of non-detectable immune measures has demonstrable effects on the analysis and interpretation of the results.

Explorations of Dopamine and Noradrenaline Activity and Negative Symptoms in Schizophrenia: Concepts and Controversies

Attempts to understand the pathophysiology of negative symptoms took off when Crow (1980a, b) described the Type I and II syndromes of schizophrenia. He proposed that the Type II form was irreversible and nondopaminergic, consisting of negative symptoms, brain atrophy, poor drug response, and outcome; Type I was the reverse, i.e., positive symptoms, absence of brain atrophy (normal ventricle brain ratio, VBR), and excellent antipsychotic drug response, and consisted of a hyperdopaminergic disorder. Mackay (1980) challenged this concept and hypothesized that Type II schizophrenia was a hypodopaminergic, Kraepelinian form of schizophrenia.

CSF levels of diazepam binding-inhibitor correlate with rem latency and slow wave sleep in schizophrenia

CPs (p < 0. IO). Although the SPs spent less time in REM sleep (p<O.O5), further REM sleep parameters, including REM latency and REM density, were not altered. In conclusion, our findings in drug-naive patients with a first episode of a schizophrenic disorder are in favour of an arousal linked disturbance at the beginning of the night sleep resulting in a delayed sleep onset and a disturbed build-up of SWS. On the other hand, we did not observe changes in REM latency or REM density in these patients.