Alan B. Douglass

Sleep in psychiatric disorders: where are we now?

Although the precise function of sleep is unknown, decades of research strongly implicate that sleep has a vital role in central nervous system (CNS) restoration, memory consolidation, and affect regulation. Slow-wave sleep (SWS) and rapid eye movement (REM) sleep have been of significant interest to psychiatrists; SWS because of its putative role in CNS energy recuperation and cognitive function, and REM sleep because of its suggested involvement in memory, mood regulation, and possible emotional adaptation. With the advent of the polysomnogram, researchers are now beginning to understand some of the consequences of disrupted sleep and sleep deprivation in psychiatric disorders. The same neurochemistry that controls the sleep-wake cycle has also been implicated in the pathophysiology of numerous psychiatric disorders. Thus it is no surprise that several psychiatric disorders have prominent sleep symptoms. This review will summarize normal sleep architecture, and then examine sleep abnormalities and comorbid sleep disorders seen in schizophrenia, as well as anxiety, cognitive, and substance abuse disorders.

Is sleep-disordered breathing associated with miscarriages? An emerging hypothesis

Sleep-disordered breathing (SDB) is a common disorder that has numerous medical consequences including cardiovascular morbidity. The clinical presentation in women is frequently vague, leading to its under-recognition in this population. Sleep is known to influence several female hormonal cycles including estrogen, progesterone, prolactin, luteinizing hormone (LH), and follicle stimulating hormone (FSH); consequently, sleep disruption may have adverse effects on female health including pregnancy. Miscarriage, defined as the loss of a pregnancy in the first trimester, occurs in one in four pregnancies; in up to half of cases, the cause may be unknown. Risk factors for miscarriage include increased age, increased weight, and a history of polycystic ovarian syndrome, all of which are also risk factors for SDB. Since SDB is frequently accompanied by sleep fragmentation and intermittent hypoxemia, we speculate that these factors may contribute to miscarriage risk. If this is the case, then treatment of SDB may be a possible intervention for subsequent pregnancies.

The effects of galantamine and buspirone on sleep structure: Implications for understanding sleep abnormalities in major depression

Rationale: The serotonergic and cholinergic systems are jointly involved in regulating sleep, but this balance is theorized to be disturbed in depressed individuals. Objective: The goal of this study was to use biological probes in healthy participants, to model the serotonergic/cholinergic imbalance of depression and its associated abnormalities in sleep structure. Methods: We tested 20 healthy female participants 18–30 years of age on four non-consecutive nights. Participants were given galantamine (a cholinergic agent), buspirone (a serotonergic agonist), both drugs together, or placebo before sleeping. Results: Buspirone suppressed tonic rapid eye movement (REM): There was a significant increase in REM latency (p < 0.001). Galantamine increased tonic REM sleep, leading to more time spent in REM (p < 0.001) and shorter REM latency (p < 0.01). Galantamine and buspirone given together were not significantly different from the placebo night by REM sleep measures, but disrupted sleep more than either drug alone. Conclusions: These findings are partially consistent with the cholinergic literature about sleep in depression, notably short REM latency, higher percentage of total sleep time spent in REM and increased sleep fragmentation. The prolonged REM latency and reduced percentage of REM with buspirone resembled the effect of selective serotonin reuptake inhibitor antidepressants on REM sleep.

Effect of atypical antipsychotics on body weight in geriatric psychiatric inpatients

Background: Studies suggest that antipsychotic-induced weight gain is not a great concern in the elderly population. This study investigated the weight change in elderly patients with various treatment duration and antipsychotics. Part 1 of the study was to determine whether atypical antipsychotics induced weight change in elderly patients. Part 2 was to determine whether certain atypical antipsychotics induced more weight change in elderly patients. Methods: In Part 1, a retrospective chart review was done on 115 geriatric inpatients. After exclusion, patients were divided into four groups: control (n = 17), new treatment (n = 18), long-term treatment (n = 13), and medication switch groups (n = 8). In Part 2, a retrospective medication review was performed on 169 geriatric inpatients. After exclusion, patients were divided into three groups: aripiprazole (n = 18), olanzapine (n = 49), and risperidone (n = 57). Body weights were obtained at two different time points. Results: No significant difference in weight change was observed among the control (1.5 kg), new treatment (0.8 kg), long-term treatment (−0.3 kg), and medication switch (1.9 kg) groups. No significant difference in weight change was observed between patients with and without dementia (0.8 and 1.1 kg, respectively). The weight change in the aripiprazole group (−2.0 kg; −2.30% from baseline) was significantly different from the weight change in the olanzapine group (0.7 kg; 1.87% from baseline; p < 0.05), but not from the risperidone group (−0.4 kg; −0.45% from baseline). Clinically significant weight gain (>7% increase in body weight) occurred in 14.3% of the olanzapine patients, a percentage significantly higher than the 3.5% in the risperidone group. Conclusion: Although atypical antipsychotics were generally weight neutral in the geriatric population, aripiprazole and olanzapine were associated with significant weight loss and weight gain, respectively.

Baclofen for narcolepsy with cataplexy: two cases.

Narcolepsy is a disabling sleep disorder characterized by daytime hypersomnolence. Those with cataplexy have spells of muscle weakness precipitated by strong emotions, especially laughter or surprise. Cataplexy treatments include antidepressants or a GABA-B agonist, gamma hydroxybutyrate (GHB). GHB is the most effective treatment for cataplexy, but is expensive and can have significant side effects. A recent report of a murine model of narcolepsy-cataplexy suggests R-baclofen has potential efficacy against cataplexy. We report on two narcolepsy patients with multiple daily cataplexy episodes, one of whom had been effectively treated with GHB, but had to discontinue it for unrelated medical reasons. Both subsequently tried baclofen and experienced almost complete resolution of cataplexy. This report suggests baclofen can be an effective treatment for cataplexy in humans and warrants further study.

Book Review: Treating Sleep Problems—A Transdiagnostic ApproachTreating Sleep Problems—A Transdiagnostic Approach. HarveyAllison G.BuysseDaniel J. New York (NY): Guilford; 2018. 192 p. US

The purpose of this book is to introduce a new and comprehensive type of cognitive behavioural treatment for insomnia (CBTi), which the authors have called “TranS-C,” for “transdiagnostic sleep and circadian intervention.” It is clearly aimed at psychologists who are already doing CBTi in their practice but who wish to have a broader set of treatments to offer. While the book has little to say about medication treatment for insomnia, it amply fulfills its purpose with a very detailed elaboration of the proposed multipronged attack on sleep disorders—it is not just a book about insomnia. The authors accurately note the modern conception of insomnia and depression as being a “two-way street,” in that sufficient sleep disruption from any cause appears to trigger depression, while depression has insomnia as one of its major symptoms. Over long follow-up, there are also other patients who demonstrate either pure insomnia or pure depression. These authors are extremely well qualified to write on this topic. Dr. Buysse is the lead author of the Pittsburgh Sleep Quality Inventory (PSQI), which is currently the most frequently used questionnaire in the world to assess subjective sleep quality. He is also a career-long author in the area of insomnia and cognitive behavioural treatment. Likewise, Dr. Harvey is an internationally respected authority in the field whose career focusses mainly on CBTi. The main thesis of the book is that existing psychological treatments for sleep disorders have been too narrowly focussed on insomnia and have not operationally included a large amount of recent neurobiological findings. The “transdiagnostic approach” that they propose is quite complex. It consists of unlinking existing treatments from particular disorders and looking at the problem much more broadly. One benefit is that patients with more serious and complex problems can be treated, such as a bipolar patient with severe insomnia and sleep apnea. Also, elements of other existing treatments have been incorporated in the method, such as chronotherapy and motivational interviewing. The major areas of focus for the new treatment are sleep schedule regularity, subjective satisfaction with sleep, alertness during the daylight hours, ability to sleep efficiently (i.e., few awakenings while in bed), timing of the patient’s sleep in the 24 hours, and sleep duration. They further subdivide the treatment into “cross-cutting modules,” “core modules,” and “optional modules.” Numerous tips and techniques for obtaining the sleep history initially are provided, as well as hints for interventions when the therapy sessions do not seem to be going well. This volume amounts to a core textbook for psychologists or other therapists doing CBTi. It is sufficiently detailed that a current practitioner could learn many of the therapy principles directly from the book, although medication treatment and continuous positive airway pressure for sleep apnea are described only briefly. Canadian Psychiatric Association

30.Reviewer rating: Good

Objective To assess the current state of sleep medicine educational resources and training offered by North American psychiatry residency programs. Methods In June 2013, a 9-item peer-reviewed Sleep Medicine Training Survey was administered to 39 chief residents of psychiatry residency training programs during a meeting in New York. Results Thirty-four percent of the participating programs offered an elective rotation in sleep medicine. A variety of innovative approaches for teaching sleep medicine were noted. The majority of the chief residents felt comfortable screening patients for obstructive sleep apnea (72%), half felt comfortable screening for restless legs syndrome (53%), and fewer than half were comfortable screening for other sleep disorders (47%). Conclusions This is the first report in the last decade to provide any analysis of current sleep medicine training in North American psychiatry residency training programs. These data indicate that sleep medicine education in psychiatry residency programs is possibly in decline.

The State of Sleep Medicine Education in North American Psychiatry Residency Training Programs in 2013: Chief Resident’s Perspective: (Brief Report)

The purposes of this chapter are to describe the REM sleep control system for researchers not primarily working in that area and to recount the history of its use in psychiatric research. For the uninitiated, there are many quirks and complexities in the psychiatric sleep literature which make it difficult to synthesize the findings of papers from different decades.

Sleep Abnormalities as a Diagnostic Tool for Major Depressive Disorder

This is an important book in the field of sleep medicine and has substantial importance for psychiatrists. In fact, the book is worth getting just to read the chapter “CLOCK Genes and Psychiatric Illness,” whose major thesis is that common psychiatric illnesses can be understood as abnormalities in the circadian rhythm and sleep homeostatic systems. This is approached through a description of the very complex system of CLOCK genes (about 20) that have been identified in rodents and found to be similar in humans. The diurnal ribonucleic acid rhythms produced by these genes control the rhythms of body temperature, melatonin, cortisol, and rapid eye movement (REM) sleep—all of which are observed to be abnormal in patients with major depressive disorder and bipolar disorder. The behaviour of animals carrying mutations of the CLOCK gene, for example, has strong correlation to that of patients with bipolar disorder: excessive late-night activity, increased reward value of appetitive stimuli, and increased dopamine neuron activity. Further, lithium has a direct effect on gene PER2, which reduces the effect of this CLOCK gene mutation. There is also a mutation of PER2 that has the effect of reducing the transcription of monoamine oxidase A, with resultant downstream effects on dopamine and serotonin. Other genes are discussed in the context of their effects on anxiety and psychotic symptoms.

Book Review: Sleep Disorders: The Genetic Basis of Sleep and Sleep DisordersThe Genetic Basis of Sleep and Sleep DisordersShawPaul, TaftiMehdi, ThorpyMichael, editors. New York (NY): Cambridge University Press; 2013. 413 p. Can

Rationale The serotonergic and cholinergic systems are jointly involved in regulating sleep but this system is theorized to be disturbed in depressed individuals. We previously reported that cholinergic and serotonergic agents induce sleep changes partially consistent with monoamine models of sleep disturbances in depression. One potential cause of disturbed neurotransmission is genetic predisposition. The G(-1019) allele of the serotonin-1A (5-HT1A) receptor promoter region predicts an increased risk for depression compared to the wild-type C(-1019) allele. Objective The goal of this study was to investigate how serotonin-1A receptor genotypes mediate sleep sensitivity to pharmacological probes modeling the serotonergic/cholinergic imbalance of depression. Methods Seventeen healthy female participants homozygous for either C (n=11) or G (n=6) alleles aged 18–27 years were tested on four nonconsecutive nights. Participants were given galantamine (an anti-acetylcholinesterase), buspirone (a serotonergic agonist), both drugs together, or placebos before sleeping. Results As reported previously, buspirone significantly increased rapid eye movement (REM) latency (P<0.001), as well as awakenings, percentage of time spent awake, and percentage of time asleep spent in stage N1 (P<0.019). Galantamine increased awakenings, percentage of time spent awake, percentage of time asleep spent in stage N1, and percentage of time asleep spent in REM, and decreased REM latency and percentage of time asleep spent in stage N3 (P<0.019). Galantamine plus buspirone given together disrupted sleep more than either drug alone, lowering sleep efficiency and percentage of time asleep spent in stage N3 and increasing awakenings, percentage of time spent awake, and percentage of time asleep spent in stage N1 (P<0.019). There was no main effect of genotype nor was there a significant multivariate interaction between genotype and drug condition. Conclusion These findings are partially consistent with the literature about sleep in depression, notably short REM latency, higher percentage of total sleep time spent in REM, lower percentage of time asleep spent in stage N3, and increased sleep fragmentation. The C/G mutation in the serotonin-1A receptor promoter region does not appear to cause noticeable differences in the sleep patterns of a relatively small sample of healthy young females. Future studies with larger sample sizes are required.