Cerebrospinal fluid prostaglandins and corticotropin releasing factor in schizophrenics and controls: relationship to sleep architecture.

Sleep abnormalities have been consistently observed in patients with schizophrenia. Elevated levels of corticotropin releasing factor (CRF) and prostaglandins (PGs) in the cerebrospinal fluid (CSF) of patients with schizophrenia have been reported, and these neurochemical substances, known to modulate sleep in experimental animals, may play a role in these sleep abnormalities. In this study, we measured PGD2, PGE2, PGF2alpha and CRF levels in the CSF of 14 unmedicated schizophrenic patients and 14 age- and sex-matched control subjects. Polysomnographic recordings were also carried out for each subject. As expected, the sleep of the schizophrenic subjects significantly differed from that of the controls; schizophrenic subjects had a longer sleep onset latency, slept less, spent fewer minutes in stage 2 sleep and had a lower sleep efficiency. We could not, however, detect any differences in CSF CRF and PG levels between normal and schizophrenic subjects, nor could we find any correlation between CSF variables and sleep parameters in the schizophrenic subjects and the non-psychiatric controls. These results do not favor the hypothesis of a role for CRF or PGs in the pathophysiology of sleep disturbances in schizophrenia.

BPRS symptom factors and sleep variables in schizophrenia.

To examine the relationship of clinical symptoms to sleep architecture, polysomnography and clinical ratings were carried out in 20 male psychiatric in-patients who met Research Diagnostic Criteria for schizophrenia. Clinical symptoms were assessed by the Brief Psychiatric Rating Scale (BPRS). Four BPRS sub-factors, i.e., 'Thinking Disturbance', 'Withdrawal/Retardation', 'Hostility/Suspiciousness', and 'Anxiety/Depression' were correlated with five components of sleep architecture, namely, sleep onset latency, total sleep time, total slow wave sleep minutes (the summation of visually scored stages 3 and 4), total REM minutes, and REM latency. Partial correlations were computed to control for the effects of age. Of the 20 correlation coefficients computed, only one was statistically significant after Bonferroni correction, namely, sleep onset latency was positively correlated with the 'Thinking Disturbance' factor. This finding is consistent with studies showing that psychotic exacerbation is associated with reduced sleep efficiency. In contrast to this cross-sectional design, longitudinal studies are more likely to clarify the relationship of sleep architecture to changes in clinical state.

Slow wave sleep and computed tomographic measures of brain morphology in schizophrenia.

To test the hypothesis that slow wave sleep in schizophrenia is inversely correlated with ventricular system volume, polysomnography and computed tomographic (CT) brain imaging were carried out in 14 psychiatric patients who met Research Diagnostic Criteria for schizophrenia (h = 11) or schizoaffective disorder (n = 3). Three measures of ventricular system volume were analyzed: (1) raw ventricular volume expressed in cm3; (2) ventricle-to-brain ratio; and (3) ventricular volume corrected for normal variation in age and head size expressed as a standardized (z) score. All three quantifications of ventricular volume were significantly and inversely correlated with visually scored measures of stage 3 and stage 4 sleep. This finding suggests that the etiology of slow wave sleep deficits in schizophrenia is related either directly or indirectly to underlying brain dysmorphology.

Middle ear muscle activity (MEMA) in schizophrenia using a noninvasive technique.

Rapid eye movement (REM) sleep middle ear muscle activity (MEMA) was recorded in four diagnostic groups: schizophrenics (n = 18), schizoaffectives (n = 8), depressives (n = 11) and healthy, nonpsychiatric controls (n = 10). Previous work suggested that schizophrenics have higher than normal rates of REM sleep MEMA; this previous study employed the MEMA recording technique of impedance audiometry, which involves a 90-dB stimulus probe tone. The present study, which utilized a silent, pressure-sensitive transducer (i.e. no acoustic stimulus), was undertaken to determine if the stimulus tone might have elicited excess MEMA in the schizophrenics. In this present study, we observed no significant differences in REM sleep MEMA among the four diagnostic groups, suggesting that REM sleep MEMA cannot be used as a biological marker to differentiate clinical disorders. This failure to replicate our previous finding of high MEMA rates in schizophrenics is likely due to sampling error; alternatively, high REM sleep MEMA rates might be elicited in a subgroup of schizophrenics with an acoustic stimulus.

The effect of chronic alprazolam on sleep and bioamine metabolites in depression.

Alprazolam administered for 43 days in doses of 6 to 10 mg/day had an antidepressant effect in four of nine depressed patients. Decreases in slow wave sleep, increases in rapid eye movement (REM) latency, and decreases in REM minutes and percent and REM sleep eye movements were found in the group as a whole. The drug had a general hypnotic effect with a trend toward increased total sleep time. Nonsignificant changes in the concentrations of 3-methyl-4-hydroxyphenylglycol and homovanillic acid in the cerebrospinal fluid (CSF) were qualitatively similar to those found after treatment with tricyclic antidepressant drugs; however, only the larger decreases in CSF 5-hydroxyindoleacetic acid achieved statistical significance. Baseline sleep and CSF metabolites and changes in these measures on drug did not predict the therapeutic effects of alprazolam.

Rapid eye movement sleep eye movements in schizophrenia and depression.

OBJECTIVE: To investigate the specificity of rapid eye movement (REM) sleep eye movement measures in schizophrenics, depressives, and nonpsychiatric controls. DESIGN: Survey. SETTING: Inpatient psychiatric hospital. STUDY PARTICIPANTS: Volunteer sample of male veterans who met Research Diagnostic Criteria (RDC) for schizophrenia (n = 21) or major depressive disorder (n = 24), or male veterans recruited from the community with no history of psychiatric illness (n = 13). Patients with a concurrent RDC diagnosis of alcoholism were excluded. After data collection, three schizophrenics, two depressives, and one nonpsychiatric control were eliminated because of two or fewer REM periods on either of the two recording nights. INTERVENTION: None. MAIN OUTCOME MEASURE: Computer-detected total night and within-night measures of REM sleep eye movement density, ie, the ratio of eye movement counts to stage REM minutes. RESULTS: Using a 95% confidence interval, schizophrenics, depressives, and nonpsychiatric controls did not differ in total night or within-night measures of eye movement density. Within nights, eye movement density increased across REM periods in the schizophrenics and nonpsychiatric controls; the depressives showed a flatter within-night distribution associated with their older age. CONCLUSIONS: A broad range of REM sleep eye movement densities characterize both schizophrenics and depressives and substantially overlaps the normal range. Abnormalities of REM sleep eye movement activity should not be considered a biological marker for affective illness.

An inexpensive alternative for recording middle ear muscle activity (MEMA) during sleep.

In past studies of middle ear muscle activity (MEMA) in sleep, one of two methods of recording has been used: an acoustic impedance bridge (AIB) or a miniaturized pressure transducer (MPT). A low-cost and less fragile piezoresistive pressure transducer was tested to determine its practicality in recording MEMA during sleep in humans. A specialized ear mold accommodating both types of pressure transducer was custom-fitted for six subjects. The sleep of each subject was analyzed epoch by epoch for one night to determine comparability of the two transducers. In no case did either transducer indicate a MEMA without confirmation by the other. It is recommended that this type of transducer would be practical for researchers interested in recording MEMA in sleep.

Middle-ear muscle activity (MEMA) and its association with motor activity in the extremities and head in sleep.

Middle-ear muscle activity (MEMA) in sleep was simultaneously recorded from both ears using extratympanic manometry. Head movement, speech movements, ankle flexion and wrist movement were monitored by electromyographic recording using surface electrodes at the back of the neck, second laryngeal notch, anterior tibialis and forearm muscle. Motor events recorded from these electrode placements were examined for correlation with MEMA to test the hypothesis that the middle-ear muscles are activated in conjunction with other motor activities, aside from eye movements, by a central motor command system. Phi coefficients were calculated for each subject; all were positive, thus indicating an association between MEMA and other noneye movement motor events. These results suggest that there is a central phasic motor system responsible for MEMA and associated phasic motor activity in sleep.

MMPI measures of impulsivity and depression correlate with CSF 5-HIAA and HVA in depression but not schizophrenia.

Recent studies have linked impulsivity with CSF concentrations of both 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA). One work found a negative correlation between the MMPI psychopathic deviate (Pd) scale and 5-HIAA in personality disordered men (Brown et al., 1982). We found that the 5-HIAA/Pd correlation extends (P less than 0.05) to unmedicated depressed patients (n = 21). A trend was found between HVA and Pd in depression. There was no relationship between either metabolite and the Pd scale in unmedicated schizophrenics (n = 24). A significant inverse correlation was found between the MMPI depression scale and CSF HVA but not 5-HIAA in the depressed patients.

Evidence for the role of serotonin in the regulation of slow wave sleep in schizophrenia.

Nocturnal sleep data and cerebrospinal fluid (CSF) concentrations of the biogenic amine metabolites were measured in 20 male schizophrenics. Consistent with other reports of a stage 4 sleep deficit in schizophrenia, measures of stage 4 sleep were low relative to normal reference data. Measures of stage 4 sleep in absolute amounts and corrected for total sleep were positively correlated with CSF concentrations of the serotonin metabolite, 5-hydroxyindole acetic acid (5-HIAA). CSF 5-HIAA was also correlated with measures of stage 3 sleep and total sleep time suggesting that serotonin may modulate the amount of slow wave sleep broadly defined and possibly sleep duration. Total stage 4 time was also correlated with the dopamine metabolite HVA; consequently, the specificity of the finding might be limited. Also, in this study, schizophrenia was used as a particular model for stage 4 deficits; however, the association of measures of stage 4 sleep with CSF levels of 5-HIAA is not thought to be specific to schizophrenia.

Sleep patterns in borderline personality disorder.

Sleep patterns of borderline patients with and without a history of affective disorder were compared to each other and to normal reference data. The three groups could not be distinguished in terms of REM latency because a wide spread of values was seen within each group. Borderlines were different from normal controls in other aspects of sleep architecture; they had less total sleep, more stage 1 sleep, and less stage 4 sleep. If one assumes that REM latency is a biological marker for mood disorder, then our results do not support the hypothesis that borderline personality disorder is a variant of affective illness. However, other data suggest that REM latency should not be used to validate the presence of affective illness.

Abnormal rapid eye movement latencies in schizophrenia.

Several previous studies have observed short rapid eye movement (REM) latencies in schizophrenic patients without major affective disorder. This study was designed to meet several of the criticisms of those previous studies. Using Research Diagnostic Criteria, we compared the sleep patterns of schizophrenic patients with those of normal controls and patients with major depressive disorder and schizoaffective disorder. All patients were medication free, and REM latency was explicitly defined using both strict and lenient criteria. Chronically ill paranoid or undifferentiated schizophrenics could not be distinguished from patients with major depressive disorder or schizoaffective disorder using any definition of REM latency. These results were not due to longer REM latency in the particular sample of patients with major depressive disorder. They had abnormally low REM latencies; however, the schizophrenic patients showed similar decrements. These data cast serious doubt on the specificity of short REM latency as a biological marker for major depressive disorder.

Testing the REM sleep phasic event intrusion hypothesis of schizophrenia.

Middle ear muscle activity (MEMA) and periorbital integrated potentials (PIPs) were recorded during rapid eye movement (REM) periods and during the 10 minutes preceding and following REM periods in normals, schizophrenic patients, and patients with schizoaffective and major depressive disorder. Contrary to the phasic event intrusion hypothesis, we observed no leakage or redistribution of MEMA or PIPs from REM into the surrounding stages of non-REM in the schizophrenic patients. Within REM, MEMA rate distinguished patients with schizophrenia from patients with schizoaffective disorder. Schizophrenic patients had higher than normal MEMA rates, whereas the schizoaffective patients had lower than normal MEMA rates.

Increased REM eye movement density in self-rated depression.

Zung depression scores were positively related to eye movement density in a sample of 19 noncomplaining young adult males. The subjects were not clinically depressed and had average scores on the Depression Scale of the Minnesota Multiphasic Personality Inventory. There was no relation of Zung depression to rapid eye movement (REM) latency, stage 3 and stage 4 sleep, or REM in the first third of the sleep period. The finding is consistent with the hypothesis of a disinhibition or phase lead of REM sleep phasic events in depression.

REM sleep eye movement activity and CSF concentrations of 5-hydroxyindoleacetic acid in psychiatric patients.

The relationship between rapid-eye-movement (REM) sleep tonic and phasic activity measures and the pre- and postprobenecid cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) was examined in a sample of 14 unmedicated psychiatric patients. The average duration of an eye movement burst and the average number of eye movements within a burst were found to be inversely related to the probenecid corrected accumulation of 5-HIAA in the CSF. These results are interpreted as indicating an association between REM burst eye movement activity and serotonin turnover in psychiatric subjects.

Middle ear muscle activity during REM sleep in schizophrenic, schizoaffective and depressed patients.

The authors measured the middle ear muscle activity during REM sleep of normal subjects (N = 13) and patients with schizophrenia (N = 11), schizoaffective disorder (N = 8), or major depressive disorder (N = 10). The rates of middle ear muscle activity for 5 schizophrenic patients were higher than the highest rates of the other groups. The patients with major depressive disorder had normal rates, and the rates of those with schizoaffective disorder were below normal. Within the schizophrenic patients, high middle ear muscle activity could not be directly attributed to background sleep disturbances, age, anxiety, depression, or diagnostic subtype.