Sleep Disturbance May Be Very Early Warning of Bipolar Risk

Daniel M. Keller, PhD

March 09, 2012

March 9, 2012 (Prague, Czech Republic) — Severely disturbed sleep patterns may be an early indicator of the risk of developing bipolar disorder (BD) and may allow early intervention, new research shows.

Speaking here at EPA 2012: 20th European Congress of Psychiatry, Phillip Ritter, MBBS, of the Clinic and Polyclinic for Psychiatry and Psychotherapy at University Hospital Carl Gustav Carus of the University of Dresden in Germany, said that sleep is highly altered in mania and depression and is the most common prodromal symptom of mania in patients with BD. Studies have shown that these patients also have a poorer quality of sleep between episodes when they are euthymic.

Even before individuals develop BD, "the picture that emerges from retrospective studies is that sleep disturbances are far more common in bipolar patients in their premorbid state compared to healthy controls," Dr. Ritter said, based on his reading of the literature.

He noted that sleep disturbances emerge in adolescence, occur far more frequently in the offspring of patients with BD, and occur several years before the first affective episode.

Dr. Ritter presented the first results of his own ongoing prospective study, called BipoSleep, which uses a structured interview and actimetry, a wrist-worn device to detect movement, from which sleep and wake periods can be determined.

Consistently Disturbed Sleep

To date, the study includes 59 participants (22 bipolar patients, 9 high-risk individuals, and 28 control participants). High risk was defined as having a first-degree relative with an affective disorder and subsyndromal mood symptoms but no previous manic episode.

For a small study, the groups were reasonably well matched for age (group mean range, 25.4 - 32.7 years), gender (57% - 78% male), and employment or student status (91% - 100%).

Of the 39 questions in the structured interview about sleep, "there was a significant difference in answers for 30 questions," Dr. Ritter reported. "So that alone seemed to be a good indicator that bipolar patients have difficulty sleeping."

When asked to rate the frequency of unrestorative sleep (0 - 6 points), healthy control participants reported a mean of 1; bipolar patients, 3; and people at high risk for BD, just above 4. In answer to a question about insomnia for at least 3 nights in a row, on a 0 - 9 scale, the score by healthy control participants was 0; by bipolar patients, 4; and by high-risk individuals, 3.

Healthy people may have an occasional night of poor sleep, "but they rarely had a series of 3 or more nights," Dr. Ritter said. "This was very common in patients with bipolar disorder, but it was also quite common in patients at high risk of bipolar disorder."

Interestingly, hypersomnia of at least 3 days' duration was also common among the BD patients and high-risk individuals compared with control participants, with average scores of 5, 9, and 0, respectively.

Altered Mood

For each of the items in the questionnaire, Dr. Ritter standardized the scores, setting the scores of healthy control participants as 1, and he plotted the scores for the BD patients, the high-risk individuals, and the control participants for each item in the questionnaire.

The greatest differences from control participants were in terms of recurrent insomnia and a heightened sensitivity to disruptions in daily sleep rhythms for both the patients and the high-risk groups.

He had expected that the high-risk group would fall somewhere between the patients with established BD and the control participants.

"But actually we were a bit surprised to see that...the results of the high-risk participants are much closer to the answers we got from patients with established bipolar disorder, which might be an indication that really sleep is altered prior to the first episode, but it's speculative," he said.

Dr. Ritter also noted that there was more profound effect of altered sleep on mood as well as altered mood on sleep for the patient group and the high-risk group. These groups also had more difficulty in maintaining a regular rhythm after disruptions in sleep rhythms.

The reported differences on the questionnaires among the 3 groups was not so profound for sleep latency (time to get to sleep), sleep duration, and awake periods per hour, and there were fairly wide individual variations within groups.

With regard to the actimetry data for 6 nights in a row, Dr. Ritter said the data did not show much difference among the groups for most of the parameters measured.

Profile Similar to BD

One significant difference was in sleep latency, with BPD patients taking longer to get to sleep, despite many of them receiving sedating medications. But they tended to sleep longer once asleep compared with control participants. They also slept more "efficiently," with little sleep fragmentation.

The fact of greater sleep duration for BD patients has also been reported in the literature, the consensus being that patients sleep ½ hour or 1 hour longer.

Dr. Ritter said that even after correcting for sedating medications in the study, sleep duration was still elevated in the BD group.

The high-risk group also had a mildly elevated length of sleep, even though they were free of medication. For most other measures, they were similar to the control group except that they had a higher level of nighttime activity than either the control participants or the BD group.

He added that a limitation of the study is that 6 nights of actimetry monitoring may not be long enough to detect other differences between the groups.

He concluded that patients with BD differ significantly from healthy control participants regarding most of their nighttime and subjective sleep habits and that "high-risk persons have a profile similar to bipolar subjects, but the differences in actimetry are not really evident over 6 nights."

Potential Risk Factor, Not a Predictor

Cristoph Correll, MD, associate professor at Albert Einstein College of Medicine and a child and adolescent psychiatrist at the Zucker Hillside Hospital in Glen Oaks, New York, chaired the session in which Dr. Ritter presented his study results.

Dr. Correll, who had no relation to the study, told Medscape Medical News that sleep is a very nonspecific item, with up to 50% of the general population having any sleep problem in a given month, so it will be necessary to find subtypes or characteristics of disturbed sleep "that might differentiate bipolar risk from non-risk."

He said using actimetry may not be feasible with every patient suspected of being at risk but may be a predictive tool for certain high-risk individuals.

"The question and the worry is always how specific are these findings?" he said. "I would at the moment see [disturbed sleep] as a risk factor or warning sign but not as a definite predictor of the illness."

Even if people at particularly high risk of developing BD could reliably be identified, Dr. Correll said it is hard to know if or what interventions could prevent the illness.

"The hope is that once you identify high-risk people and you do some general preventive measures or early targeted measures, which would include healthy lifestyle, no substance use, sleep hygiene, and then also stress reduction and targeting anxiety and depression, maybe even with nonpharmacologic treatments, that should already help. Then more pharmacologic interventions can only be tested and developed once we can validly identify high-risk people," he said.

He added that no one yet knows how circadian rhythm and BD risk interact — whether underlying illness exists first and then disrupts circadian rhythm or whether circadian rhythm disruption is 1 factor that pushes people into mania and BD.

"We don't know that," Dr. Correll said. "We just know that circadian rhythm abnormalities are associated with mood disorders, and we need to try to get that under control in order to hopefully then also attenuate the risk and the expression of the illness."

The study did not receive any commercial funding. Dr. Ritter has disclosed no relevant financial relationships. Dr. Correll has been a consultant and/or advisor to or has received honoraria from Actelion, Alexza, the American Academy of Child and Adolescent Psychiatry, AstraZeneca, Biotis, Bristol-Myers Squibb, Cephalon, Desitin, Eli Lilly, Gerson Lehrman Group, GSK, IntraCellular Therapies, Lundbeck, Medavante, Medscape, Merck, Novartis, Ortho-McNeill/Janssen/J&J, Otsuka, Pfizer, ProPhase, Sunovion, Takeda, and Teva. He has received grant support from BMS, Feinstein Institute for Medical Research, Janssen/Johnson & Johnson, the National Institute of Mental Health, the National Alliance for Research in Schizophrenia and Depression, and Otsuka.

EPA 2012: 20th European Congress of Psychiatry. Abstract AS04-01. Presented March 4, 2012.


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