Contributor Information Hidenobu Suzuki, Department of Psychiatry, Tanzawa Hospital, 557 Horiyamashita, Hadano, Kanagawa, 259-1304, Japan. Yuichi Inoue, Shakomae Kokorono Clinic [Y.I.], Tokyo, Japan. Akiyoshi Nishiyama, Department of Psychiatry, Tokai University Hachioji Hospital [A.N.], Tokyo, Japan. Katsunaka Mikami, Department of Psychiatry, Course of Specialized Clinical Science, Tokai University School of Medicine Inhibitors,research,lifescience,medical [K.M.], Kanagawa, Japan. Keishi Gen, Department of Psychiatry, Seimo Hospital [K.G.], Gunma, Japan.
Sleep disturbances constitute a core symptom of bipolar disorder (BD). Up to 90% of individuals

experiencing a major depressive episode (MDE) complain of sleep disturbance, typically sleep-onset insomnia, frequent nocturnal arousals, and early morning Inhibitors,research,lifescience,medical awakenings [Tsuno et al. 2005]. Insomnia is a risk factor for the development of MDEs and may precede the onset of depression in those with recurrent illness [Breslau et al. 1996; Ford and Cooper-Patrick, 2001]. Sleep disturbance is also a risk factor for suicide [Liu and Buysse, 2005]. Hence, patient care and treatment should include an assessment focusing on sleep function, as well as appropriate measures to improve and optimize sleep architecture. Normal sleep Inhibitors,research,lifescience,medical architecture can be separated into rapid eye movement (REM) and non-REM (NREM) sleep, which

alternate in a cyclic fashion. The first hours of sleep include a high percentage of time spent in the Inhibitors,research,lifescience,medical four stages of NREM sleep. Stages 1 and 2 are described as a transition from drowsiness to light sleep, whereas stages 3 and 4 are collectively known as slow wave sleep (SWS). As sleep progresses, more time is spent in the REM stage. This normal sleep architecture is altered in BD. Sleep of patients with bipolar depression Inhibitors,research,lifescience,medical is fragmented by REM disinhibition, reduced SWS duration, and impaired sleep continuity [Kupfer, 1995]. REM disinhibition features shortened latency to REM sleep and prolonged total REM duration [Kupfer, 1995]. Impairments in sleep continuity include prolonged sleep

latency, and increased number of intermittent arousals and early morning awakenings [Argyropoulos and Wilson, 2005]. The reciprocal interaction model assumes that Rolziracetam sleep disturbance in depression is due to dysPonatinib function of the central neurotransmitter systems: acetylcholine (Ach), norepinephrine (NE) and serotonin (5-HT), all of which modulate mood and sleep wakefulness [Hobson et al. 1975]. Ach stimulates REM sleep, whereas NE and 5-HT inhibit it. Depression is strongly associated with an overactive cholinergic system and deficient monoaminergic transmission. This imbalance has been held responsible for disinhibiting REM sleep and may also promote increased wakefulness resulting in reduced sleep continuity and efficiency [Sharpley et al. 2005].