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.

Polysomnographic studies in patients referred for ECT: pre-ECT studies.

Forty-one patients referred for electroconvulsive therapy (ECT) were evaluated with a standardized clinical protocol and had polysomnographic studies performed pre-ECT after 10 or more days drug free. Clinical evaluations were performed by blind investigators and included the Research Diagnostic Criteria and the Hamilton Rating Scale for Depression (HRSD). Patients were categorized according to the clinical response. Thirty patients (73%) reached a post-ECT HRSD < or = 10, whereas 21 of them (51.2%) reached a post-ECT HRSD score < or = 6. Sleep-onset rapid eye movement (SOREM) periods were present in 27 (66%) of the patients. Few polysomnographic variables differentiated between excellent responders and patients with residual symptoms. Older patients had significantly more disrupted polysomnographic study parameters. Although present in a significant proportion of patients, baseline SOREM was not a factor in outcome.

Biological predictors of suicidality in schizophrenia.

The objective of this study was to determine whether polysomnographic rapid eye movement (REM) sleep abnormalities and cortisol response to the dexamethasone suppression test (DST) differentiate between schizophrenic patients with and without a history of suicidal behaviour. We assessed a sample of 96 schizophrenic in-patients at the end of a 2-week medication-free period with the DST, polysomnography, and an extensive clinical assessment battery. Patients exhibiting suicidal behaviour were significantly more likely to have increased total REM time and increased total REM activity. We found no significant relationship between suicidal behaviour and DST non-suppression. This study confirms a previous finding suggesting an association between REM sleep abnormalities and suicidal behaviour in schizophrenia. It is postulated that this observed association may be related to serotonergic dysfunction in schizophrenia.

A treatment and withdrawal trial of besipirdine in Alzheimer disease.

Besipirdine hydrochloride (HP 749) is an indole-substituted analog of 4-aminopyridine. Besipirdine enhances both cholinergic and adrenergic neurotransmission in the central nervous system. The present study examined the efficacy and tolerability of two doses of besipirdine (5 and 20 mg b.i.d.) in 275 patients with Alzheimer disease during 3 months of treatment and for 3 months after withdrawal of treatment. Assessment after withdrawal of treatment was used in an effort to distinguish persistent efficacy attributable to a neuroprotective mechanism from reversible symptomatic efficacy. Besipirdine was generally well tolerated. The level of performance on the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog) was sustained during 3 months of treatment with besipirdine, whereas some deterioration in the performance of patients treated with placebo was observed over the same period. The small difference between active and placebo treatment groups approached, but did not reach statistical significance in the primary intent-to-treat analysis (p = 0.067); analysis of patients who completed all assessments was supportive (p = 0.031). Global ratings using the Clinician Interview-Based Impression of Change did not detect a besipirdine treatment benefit, possibly because of an adverse effect on mood and behavior in some patients. A high ratio of adrenergic to cholinergic potency may have resulted in the adverse effects of besipirdine and hence its failure to support the hypothesis that multiple neurotransmitter treatment may be more efficacious than monotherapy. The efficacy apparent on the ADAS-Cog after 3 months of treatment did not persist 3 months after withdrawal of treatment, suggesting that the benefit was symptomatic. This study provides a practical example of the use of treatment withdrawal assessment to distinguish neuroprotective from symptomatic efficacy.

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.

Sleep Electroencephalographic Studies After ECT.

Forty-one patients with major depressive disorder were treated with electroconvulsive therapy (ECT). Sleep polysomnography studies (SPSs) were performed after the course of ECT. The hypotheses tested were that age is a significant factor in post-ECT SPS results and that some SPS parameters are correlates of outcome of ECT. An interaction between age and response to ECT could not be identified; however, older patients demon strated significantly disrupted sleep post-ECT. Response to ECT was associated with lower REM activity and lower REM density. Sleep-onset REM periods post-ECT were observed in almost 50% of the patients regardless of age. The SPS monitoring of recovery after a course of ECT may identify sleep correlates of response to ECT and variables associated with poorer longitudinal outcome.

Schizophrenia, narcolepsy, and HLA-DR15, DQ6.

A strong association between HLA-DR2, DQ1 and narcolepsy-cataplexy has been known since 1986. In 1990 a subdivision (HLA-DR15, DQ6) was shown to be equally associated. Narcolepsy symptoms include rapid eye movement (REM)-sleep intrusion hallucinations during the day. Some narcoleptics may be so hallucinated that they become delusional and receive a diagnosis of schizophrenia. Fifty-six inpatient schizophrenics and 56 normal controls were compared to see if there was an excess of the narcolepsy-associated antigens (NAA) among schizophrenics. Patients had frequency of the NAA 3.89 times higher than controls. After a subset was studied by night (n = 9) and day (n = 7) polysomnography, two patients were found to be true narcoleptics. Their psychosis improved with treatment for narcolepsy. When NAA(+) and NAA(-) schizophrenics were compared, the NAA(+) subgroup had significantly higher Brief Psychiatric Rating Scale (BPRS) scores and more hospitalizations. There were no effects attributable only to gender or race. We conclude that narcolepsy can simulate schizophrenia in some cases, and that even in nonnarcoleptic patients, the HLA-DR15,DQ6 antigens mark a group of severe schizophrenics that merits further study.

Sleep-disordered breathing in alcoholics: association with age.

Sleep apnea and related disorders are not uncommon in abstinent alcoholics. We assessed the relationship between age and the presence and severity of sleep-disordered breathing in alcoholism by performing one night of polysomnography on 75 abstinent alcoholic subjects undergoing treatment for alcoholism. Sleep-disordered breathing (defined as 10 or more apneas plus hypopneas/hr of sleep) was present in 17% of 66 men aged 22-76 and in 0 of 9 women aged 28-63 years. Three percent of men under age 40 years had sleep-disordered breathing compared with 25% of men between ages 40-59 and 75% of those above age 60. Although alcoholics with sleep-disordered breathing had a higher body mass index than those without, the increased frequency over age 40 was statistically significant after controlling for the effects of body mass index. Sleep in subjects with sleep-disordered breathing was significantly more disturbed than in subjects without sleep-disordered breathing. Our findings suggest that sleep-disordered breathing in older male alcoholics is more prevalent than has been reported in most studies of normal men and that the increase in sleep-disordered breathing that occurs with age in alcoholics is greater than the age-related increase in sleep-disordered breathing that occurs in healthy elderly men. Furthermore, sleep-disordered breathing is a significant contributor to sleep disturbance in a substantial proportion of male alcoholics above the age of 40 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol use and periodic limb movements of sleep.

Alcohol causes significant sleep disturbance but the causes are not well understood. We investigated the relationship between alcohol use and periodic limb movements in a large population of patients at a sleep disorders center. The likelihood of having a clinically significant number of periodic leg movements (more than 20 per hour of sleep) was increased 3-fold in women who consumed two or more alcoholic drinks per day compared with those who did not (25% versus 8%). A similar relation was found among men (22% versus 13%). In addition, women who consumed two or more drinks per day were more likely to report symptoms of restless legs and to be diagnosed with restless legs syndrome. These findings suggest that periodic leg movements contribute to sleep disturbance in a significant proportion of alcohol users. Alcohol use may increase the frequency of periodic leg movements in susceptible individuals. On the other hand, subjects with symptoms related to periodic leg movements may be using alcohol to relieve symptoms, or the movements may be secondary to alcohol-induced sleep disturbance.

Sleep architecture and sleep apnea in patients with Cushing's disease.

Patients with Cushing's syndrome (CS) frequently have sleep complaints. We evaluated sleep polysomnographically in 22 patients, including 17 with pituitary-ACTH-dependent Cushing's disease (CD) and five with CS from an adrenal tumor. Data were compared to healthy controls of comparable age. Seven patients (32%) demonstrated at least mild sleep apnea (> or = 9.4 events/hour), and four of 22 (18%) had > or = 17.5 events/hour. The apneic CD and CS patients had a trend for a greater complaint of excessive daytime sleepiness. Both apneic and nonapneic groups had considerable snoring and obesity. The electroencephalographic (EEG) sleep of nonapneic patients was compared to that of normal subjects. Nonapneic CD patients differed strikingly from healthy volunteers in sleep continuity and architecture, demonstrating lighter, fragmented sleep. Rapid eye movement (REM) sleep in CD patients bore many similarities to the sleep of patients with major depression, with REM latency being significantly shortened and REM density significantly increased. Continued examination of EEG sleep in CD patients may shed light on similarities in pathophysiology between CD and major depression, disorders which are characterized by both a dysfunction of the hypothalamic-pituitary-adrenal axis and alterations in mood.

Neuropsychological function and REM sleep in schizophrenic patients.

To test the hypothesis that rapid eye movement (REM) sleep in schizophrenic patients is associated with cognitive function, we studied 18 schizophrenic inpatients by means of electroencephalograms taken during sleep in their own hospital beds after a minimum 2-wk medication withdrawal period. Patients underwent neuropsychological tests to measure memory function and other aspects of cognitive performance. REM sleep measures demonstrated positive and negative correlations with cognition and memory measures, depending on when REM occurred after sleep onset. Minutes of REM sleep and REM density in the first period correlated negatively with performance, while REM minutes occurring after the first REM period correlated positively with neuropsychological performance. Further work should test whether phasic REM sleep regulation at the beginning of the night plays a compensatory role for neuropsychological dysfunction in schizophrenics.

EEG sleep in Cushing's disease and Cushing's syndrome: comparison with patients with major depressive disorder.

Because patients with Cushing' syndrome (CS) and Major depressive disorder (MDD) share features of hypercortisolism and the depressive syndrome, we compared electro-encephalographic (EEG) sleep in patients with pituitary-ACTH-dependent Cushing's syndrome (Cushing's disease, CD), patients with ACTH-independent Cushing's syndrome (AICS), patients with major depressive disorder (MDD), and normal subjects. There were substantial similarities in the abnormal polysomnography profiles of patients with CD, AICS, and MDD. All three patient groups demonstrated poorer sleep continuity, shortened rapid eye movement (REM) latency, and increased first REM period density compared with normal subjects. In addition, AICS patients and MDD patients had elevated REM activity and density. These findings are discussed in terms of models of pathophysiology that relate abnormalities in sleep, mood, and hypothalamic-pituitary-adrenal function.

Utility of an oral diffusion sink (ODS) device for quantification of saliva corticosteroids in human subjects.

Measurement of cortisol by assay of single blood or saliva samples is inherently imprecise due to the episodic secretion of cortisol. In addition, assay of blood usually quantifies total cortisol, rather than separating free hormone, which is proportionately the much smaller fraction. Furthermore, the free fraction may be disproportionately higher in hypercortisolism. Urinary free cortisol is one measure that provides both a time integral and a focus on the free fraction, but it is inconvenient and prone to collection error in unsupervised ambulatory subjects. The Oral Diffusion Sink (ODS) apparatus takes up corticosteroids from saliva according to first-order kinetics and may provide a practical alternative. We assessed the utility of the ODS in a study of seven healthy volunteers admitted to the CRC for three days. Data on day two from 0700-1100 h and 1100-1500 h were compared between the ODS and three other means of assessing cortisol: urinary free cortisol (UFC), blood, and saliva. The subjects all tolerated wearing the ODS device without any complaint. High correlations were observed between ODS values vs. data for UFC, plasma, and saliva determinations. In summary, the ODS device was well tolerated and collected reliable corticosteroid data, and thus provides a new, non-invasive methodology for studies of HPA function in health and disease.

Electroencephalographic sleep abnormalities in schizophrenia. Relationship to positive/negative symptoms and prior neuroleptic treatment.

Polysomnographic abnormalities in schizophrenia are not well characterized and their associations with schizophrenic symptomatology have not been adequately assessed. To address these issues, we recorded electroencephalographic sleep in 20 drug-naive schizophrenics, 20 drug-free but previously medicated schizophrenics, and 15 normal controls. Drug-naive and previously medicated patients had significantly greater impairment of sleep continuity and shorter rapid eye movement latency when compared with controls. In the previously medicated group, findings were significantly influenced by duration of drug-free status. Rapid eye movement latency was inversely correlated with the severity of negative symptoms (r = -.52) but was unrelated to depressive symptoms. Slow-wave sleep did not differ between schizophrenic patients and normal controls and was unrelated to any clinical parameter. Mechanisms underlying the observed associations between rapid eye movement sleep abnormalities and negative symptoms in the acute phase of schizophrenic illness need to be explored.

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.

Muscarinic cholinergic hyperactivity in schizophrenia. Relationship to positive and negative symptoms.

Based on the implication of increased muscarinic ACh activity in the production of negative symptoms, the association of decreasing cholinergic activity with positive symptoms, and the covariance of positive and negative symptoms in the psychotic phase of schizophrenia, a model of (DA) dopaminergic/(ACh) cholinergic interactions in schizophrenia was recently formulated. It suggests that DA/ACh balance is of central importance in schizophrenic pathophysiology and that muscarinic ACh activity increases in an attempt to maintain this balance in the face of increasing DA activity that occurs in the psychotic phase of the illness. The model further suggests that the muscarinic system exerts a damping influence on the emergence of positive symptoms associated with DA hyperactivity, but that this compensatory increase in muscarinic activity is accompanied by an intensification of negative symptoms. In the present study, we tested two important postulates of this model. We tested the prediction that muscarinic activity is increased in schizophrenia by comparing the effect of biperiden, an antimuscarinic M-1 agent, on REM latency in 12 drug-free schizophrenic inpatients and matched normal controls. We found that biperiden caused a smaller increase in REM latency in schizophrenic patients, suggesting that muscarinic activity is increased in schizophrenia. We tested the prediction that an anticholinergic agent would increase positive symptoms and decrease negative symptoms by studying the effect of 8 mg of biperiden/day for 2 days on positive and negative symptoms (assessed by the BPRS) in 30 medication-free schizophrenic inpatients.(ABSTRACT TRUNCATED AT 250 WORDS)