Kathleen L. Benson

An Actigraphic Comparison of Sleep Restriction and Sleep Hygiene Treatments for Insomnia in Older Adults

We compared the efficacy of sleep restriction therapy combined with sleep hygiene, nap modification of sleep restriction therapy combined with sleep hygiene, and sleep hygiene alone as treatments for insomnia in 39 community-dwelling men and women 55 years and older. We used the wrist actigraph as an objective outcome measure for all subjects at baseline, end of treatment, and 3-month follow-up; polysomnography (PSG) was conducted in a subgroup of subjects. Although subjects appeared to follow restriction instructions through follow-up, we found few between-group differences in treatment efficacy. Lack of treatment effect might be explained by the efficacy of HYG as a treatment in itself and the relatively low symptom level in these healthy older poor sleepers. At baseline, actigraphic results were found to correlate more highly than sleep log data with PSG in our sample. Actigraphic total sleep time, in particular, was highly correlated with PSG. (J Geriatr Psychiatry Neurol 2000; 13:17-27).

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.

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.

CSF hypocretin-1 levels in schizophrenics and controls: relationship to sleep architecture

Hypocretins/orexins are newly identified peptides of hypothalamic origin. Hypocretin deficiency is involved in the sleep disorder narcolepsy, suggesting the importance of hypocretin neurotransmission for the regulation of sleep. Hypocretin is known to excite midbrain dopaminergic neurons and to induce hyperactivity and stereotypy in animals. Altered hypocretin neurotransmission might therefore be involved in schizophrenia, since an involvement of dopaminergic mechanisms and an association with sleep disturbance are well demonstrated in patients with schizophrenia. Hypocretin is also known to affect the hypothalamic-pituitary-adrenal axis by stimulating the release of corticotropin releasing hormone (CRH). In the current study, we measured CSF hypocretin levels in 12 controls and 13 patients with chronic schizophrenia associated with moderate sleep disturbance, such as longer sleep onset latency, decreased total sleep time and decreased sleep efficacy. No difference in CSF hypocretin levels between schizophrenia and control subjects was found. CSF hypocretin levels were positively correlated with CSF CRH levels in the patient, control and combined subject populations, but the correlation did not reach statistical significance in any population. The hypocretin levels in schizophrenic patients were, however, positively and significantly correlated with sleep latency, one of the most consistent sleep abnormalities seen in schizophrenia. This correlation was not significant in controls, and no other significant correlation between CSF hypocretin levels and any measure of sleep architecture in either patients or controls was observed. Further studies of whether CNS hypocretin neurotransmission is involved in sleep and neuroendocrine abnormalities seen in patients with schizophrenia and other psychiatric conditions are warranted.

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.

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.

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.

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.