Cholinergic regulation of mood and REM sleep: potential model and marker of vulnerability to affective disorder

Abstract

To test the hypothesis that depression and REM sleep share common cholinergic mechanisms the authors administered arecoline 25 min after completion of the first REM period to 14 patients with remitted bipolar affective disorder, 15 normal controls, and 5 subjects with a personal or family history of affective disorder. The second REM period occurred significantly sooner in the remitted patients than in the normal controls. The patients also had a significantly higher density of eye movements during the first REM period and a higher percentage of REM sleep. The authors believe that increased cholinergic sensitivity and REM density may be biological markers of increased vulnerability to bipolar affective illness.

The effect of mood on sleep onset latency and REM sleep in interepisode bipolar disorder.

“…Finally, in regard to the REM variables, the bipolar group exhibited higher REM density compared to the control group. Tentatively, this result is consistent with previous findings of REM hyperactivity in bipolar disorder (Sitaram, Nurnberger, Gershon, & Gillin, 1982). …”

“…There was also an interesting nonsignificant trend of a Group × Mood interaction in which the bipolar group’s length of first REM period decreased on the sad, compared to baseline, nights, whereas the control group’s length of first REM period increased on the sad, compared to baseline, nights. These findings are again consistent with previous research (Sitaram et al, 1982) and suggest, in combination with the happy REM density result, that REM density in particular may be heightened in interepisode bipolar disorder. The results also raise the possibility that the bipolar group may have exhibited an adaptive increase in REM density following a sad mood (as did the control group) but that this attempt to regulate mood during sleep was offset by the shorter length of REM in the bipolar group, relative to the control group.…”

Variants in Ion Channel Genes Link Phenotypic Features of Bipolar Illness to Specific Neurobiological Process Domains

“…Sleep disturbances, including an increased or a decreased need for sleep, an altered sleep/wake cycle, an altered REM onset latency, and difficulty falling asleep are seen not only during mood episodes but also during the euthymic state [119,120]; such changes are also found in those who are at high risk of developing BD [121]. Increased cholinergic sensitivity and REM density were noticed in remitted bipolar patients in response to the cholinergic drug arecoline [122]. A longer sleep onset latency and an altered REM onset latency are seen in both BD patients and at-risk relatives, and the latter may be the best candidates for an endophenotypic abnormality in the area of sleep [123].…”

Insomnia Comorbid to Severe Psychiatric Illness

“…With regard to specific sleep characteristics, studies have shown that inter-episode BD patients had longer sleep onset latency (9, 27, 28), longer and more variable periods of wakefulness during the night (29), more nighttime awakenings (28, 30), increased sleep duration (27), poorer sleep efficiency (23, 28), and more night-to-night variability of sleep patterns (27) relative to healthy adults. During the inter-episode period, two studies have found evidence for increased REM density in both unmedicated (31) and medicated bipolar samples (32). However, one study found no differences between sleep architecture in healthy adults and inter-episode bipolar participants (30).…”