Alan S. Eiser

Phasic and enduring negative symptoms in schizophrenia: biological markers and relationship to outcome.

Negative symptoms have been associated with poor response to neuroleptics, enlarged ventricles, cognitive impairment, and poor outcome in schizophrenia. These associations appear, however, to be dependent on the phase of study, suggesting that acute-phase (phasic) negative symptoms may be pathophysiologically distinct from enduring negative symptoms that persist through the residual phase. To compare correlates of enduring and phasic negative symptoms, we studied 60 drug-free schizophrenic patients (DSM-III-R and SADS/RDC) at baseline, 4 weeks after neuroleptic treatment, and assessed the 1 year outcome. We rated positive and negative symptoms at baseline and 4 weeks after treatment. At baseline, premorbid function, neuropsychological function, ventricle-brain ratio (VBR) and symptom response to an anticholinergic agent were assessed, and a two-night sleep EEG and 1mg dexamethasone suppression test (DST) were conducted. Phasic negative symptoms were defined as the change in negative symptoms (baseline to 4 weeks) and enduring negative symptoms as severity of negative symptoms at 4 weeks. Patients had varying proportions of phasic and enduring symptoms; the two did not define distinct subgroups. Phasic negative symptoms were significantly correlated with global treatment response, positive symptom treatment response, response to anticholinergic agent, baseline post-dexamethasone cortisol, and shortened REM latency. Enduring negative symptoms were significantly correlated with residual positive symptoms and global psychopathology, VBR, poor performance on neuropsychological testing, decreased slow-wave sleep, poor premorbid function, and poor 1 year outcome. These data suggest that phasic negative symptoms and enduring negative symptoms may be caused by different pathophysiological mechanisms.

Effect of neuroleptic treatment on polysomnographic measures in schizophrenia

To study the effects of neuroleptic therapy on sleep EEG variables in schizophrenia, as well as the clinical correlates of these variables, we performed polysomnographic (PSG) studies on 14 schizophrenic inpatients before and during neuroleptic therapy. Sleep continuity measures improved after 3 weeks of neuroleptic therapy, showing decreased sleep latency and improved sleep efficiency. REM latency increased with treatment, although half the patients continued to exhibit REM latencies less than 60 min. Other sleep stages and measures of REM sleep (density, activity, number of periods) did not appear to change with neuroleptic treatment. At baseline, REM latency had strong negative correlations with BPRS and SANS scores, but with 3 weeks of such treatment, this association disappeared. Further work is needed to distinguish direct medication effects from the effects of the changing clinical state on PSG measures.

Clinical correlates of sleep onset rem periods in depression

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Association between abnormal REM sleep and negative symptoms in schizophrenia

Although shortened rapid eye movement (REM) sleep latency, increased REM density, and decreased slow-wave sleep (SWS) are considered characteristic features of endogenous depression (Kupfer et al., 1978), several studies have reported similar findings in schizophrenic patients (reviewed in Zarcone et al., 1987). The latter observed that on the basis of REM abnormality, medication-free schizophrenic patients were indistinguishable from patients with major depression. The precise implications of these sleep findings in schizophrenia are unclear. The present study was conducted to evaluate the frequency and nature of abnormalities in the sleep electroencephalogram (EEG) in a group of medicationfree schizophrenic patients and to investigate the association of such abnormalities with positive, negative, and depressive symptoms in schizophrenia.

The Cholinergic System in Schizophrenia Reconsidered: Anticholinergic Modulation of Sleep and Symptom Profiles

The role of the cholinergic system in schizophrenia remains controversial. A series of investigations are reviewed that describe the effects of pharmacological manipulation of the cholinergic system on schizophrenia symptomatology and whether putative measures of the cholinergic system are altered in schizophrenia. The effects of biperiden (an anticholinergic agent) on positive and negative symptoms of schizophrenia and on rapid eye movement (REM) latency and other sleep measures were assessed. Biperiden produced a significant increase in positive symptoms and a decrease in negative symptoms. REM latency was significantly shorter in schizophrenic patients and increased in both groups following biperiden. REM density decreased in a dose-dependent manner following biperiden in schizophrenic patients, but not in normal controls. The slope of REM density plotted against biperiden dose was inversely related to plasma homovanillic acid (HVA), an index of dopamine (DA) activity, in schizophrenic patients. These results further implicate the cholinergic system in schizophrenia pathophysiology and suggest a role for DA-acetylcholine (ACh) interactions in the production of sleep abnormalities and expression of positive and negative symptoms in schizophrenia.

Shortened REM latency PostECT is associated with rapid recurrence of depressive symptomatology

Electroconvulsive therapy (ECT) is highly effective in the treatment of major depressive disorder (MDD). The 1-year relapse rates are reported to be high and in the 30%-60% range, however. To test whether polysomnography (PS) can identify patients with a propensity for relapse we studied 20 patients, responders to a course of ECT, with PS studies. All patients met baseline diagnostic criteria for MDD, were treated with ECT following standardized protocols, had PS studies performed after the course of ECT in a medication-free state, received maintenance antidepressants postECT, and were followed periodically with phone interviews. The recurrence of depressive symptoms was determined at 3 months and 6 months after discharge. Fifty-five percent of the patients were symptomatic when evaluated 6 months after the ECT. Sleep Onset rapid eye movement (REM) periods were identified in 55% of the patients. As a group, patients who had experienced a recurrence of depressive symptoms by 6 months after discharge, had significantly shorter REM latencies after the course of ECT. A shorter REM latency after ECT identified patients who at six months demonstrated significant depressive symptomatology. Shortened REM latency after ECT in patients with MDD appears to be a correlate of vulnerability for relapse.

Monitoring of antidepressant response to ECT with polysomnographic recordings and the dexamethasone suppression test.

Ten patients treated with electroconvulsive therapy (ECT) only were followed with serial sleep polysomnographic recordings and dexamethasone suppression tests (DSTs). Both biological correlates of depression showed improvement with ECT. The use of serial sleep measures and serial DSTs in monitoring the clinical response to ECT is discussed.

Sleep-onset rapid eye movement after electroconvulsive therapy is more frequent in patients who respond less well to electroconvulsive therapy

The response to electroconvulsive therapy (ECT) was monitored with sleep polysomnography studies (SPS) performed pre- and post-ECT, in 25 patients with major depressive disorder (MDD). Patients included in this study met research diagnostic criteria for MDD and had been free of psychotropic medication for at least 10 days before SPS were performed. We compared ECT responders and nonresponders on SPS, demographic, and clinical parameters. Many SPS parameters, regardless of the clinical response, changed significantly with ECT. The presence of delusions was significantly associated with SOREM post-ECT. The presence of sleep-onset REM periods post-ECT was associated with poor response to ECT. SPS performed during a course of ECT may help identify patients at risk of responding less well to this modality of treatment.

Serial Monitoring of Antidepressant Response to Electroconvulsive Therapy with Sleep EEG Recordings and Dexamethasone Suppression Tests

The study of the biological correlates of major depressive disorder (MDD) has received great impetus in recent years. Electroencephalographic (EEG) sleep measurements and the Dexamethasone Suppression Test (DST) have been among the most studied and productive of these biological correlates. Commonly described EEG sleep abnormalities in MDD include shortened rapid eye movement (REM) latency, increased REM density, decreased delta sleep, decreased sleep efficiency, and decreased total sleep time (Kupfer and Thase 1983; Gillin et al. 1984). With EEG sleep measurements, used individually or through discriminant analysis, the sensitivity, specificity, and diagnostic confidence for primary endogenous depression ranges from 61% to 90%, 80% to 100%, and 83% to 100%, respectively (Kupfer and Thase 1983). Similar findings have been described for the DST in MDD (Carroll et al. 1981). Thus, both the sleep EEG and the DST can be used to support the

Sleep-onset REM period in paranoid schizophrenia

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