Jennifer C. Kanady

The critical role of sleep spindles in hippocampal-dependent memory: a pharmacology study

An important function of sleep is the consolidation of memories, and features of sleep, such as rapid eye movement (REM) or sleep spindles, have been shown to correlate with improvements in discrete memory domains. Because of the methodological difficulties in modulating sleep, however, a causal link between specific sleep features and human memory consolidation is lacking. Here, we experimentally manipulated specific sleep features during a daytime nap via direct pharmacological intervention. Using zolpidem (Ambien), a short-acting GABAA agonist hypnotic, we show increased sleep spindle density and decreased REM sleep compared with placebo and sodium oxybate (Xyrem). Naps with increased spindles produced significantly better verbal memory and significantly worse perceptual learning but did not affect motor learning. The experimental spindles were similar to control spindles in amplitude and frequency, suggesting that the experimental intervention enhanced normal sleep processes. Furthermore, using statistical methods, we demonstrate for the first time a critical role of spindles in human hippocampal memory performance. The gains in memory consolidation exceed sleep-alone or control conditions and demonstrate the potential for targeted, exceptional memory enhancement in healthy adults with pharmacologically modified sleep.

Treating Insomnia Improves Mood State, Sleep, and Functioning in Bipolar Disorder: A Pilot Randomized Controlled Trial

OBJECTIVE To determine if a treatment for interepisode bipolar disorder I patients with insomnia improves mood state, sleep, and functioning. METHOD Alongside psychiatric care, interepisode bipolar disorder I participants with insomnia were randomly allocated to a bipolar disorder-specific modification of cognitive behavior therapy for insomnia (CBTI-BP; n = 30) or psychoeducation (PE; n = 28) as a comparison condition. Outcomes were assessed at baseline, the end of 8 sessions of treatment, and 6 months later. This pilot was conducted to determine initial feasibility and generate effect size estimates. RESULTS During the 6-month follow-up, the CBTI-BP group had fewer days in a bipolar episode relative to the PE group (3.3 days vs. 25.5 days). The CBTI-BP group also experienced a significantly lower hypomania/mania relapse rate (4.6% vs. 31.6%) and a marginally lower overall mood episode relapse rate (13.6% vs. 42.1%) compared with the PE group. Relative to PE, CBTI-BP reduced insomnia severity and led to higher rates of insomnia remission at posttreatment and marginally higher rates at 6 months. Both CBTI-BP and PE showed statistically significant improvement on selected sleep and functional impairment measures. The effects of treatment were well sustained through follow-up for most outcomes, although some decline on secondary sleep benefits was observed. CONCLUSIONS CBTI-BP was associated with reduced risk of mood episode relapse and improved sleep and functioning on certain outcomes in bipolar disorder. Hence, sleep disturbance appears to be an important pathway contributing to bipolar disorder. The need to develop bipolar disorder-specific sleep diary scoring standards is highlighted.

Actigraphic assessment of a polysomnographic-recorded nap: a validation study

This study aimed to determine if actigraphy could differentiate sleep and wake during a daytime nap and no‐nap rest period. Fifty‐seven subjects participated in the study; 30 subjects were in the nap group and the remaining 27 in the no‐nap comparison group. All subjects wore actigraphs while simultaneously undergoing polysomnography (PSG). Three actigraphic sensitivity levels (high, medium, low) and two interval duration minimums (15 and 40 min) were used to score the nap and no‐nap data. The variables examined included total sleep time (TST), sleep latency (SL), wake after sleep onset (WASO) and sleep efficiency (SE). The Bland–Altman technique was used to determine concordance. Epoch‐by‐epoch analysis examined actigraphic accuracy, sensitivity and specificity. For the naps, all actigraph settings except low‐40 showed significant correlations with TST. The high and medium settings predicted SE significantly and the high settings predicted SL significantly. Bland–Altman analyses demonstrated high settings overestimated TST while high and medium settings overestimated SE. Overall, for the nap condition accuracy for the actigraph was 82–86%, sensitivity was 92–96% and specificity was 40–67%. In the no‐nap condition, accuracy for the actigraph was 60–84%, sensitivity was 47–78% and specificity was 60–86%. Medium‐40 and low‐40 were the only settings that did not misidentify sleep in the no‐nap condition. These results suggest that actigraphy can predict TST, SE and SL reliably, depending upon parameter settings, and actigraphy is a highly sensitive but not specific measure for daytime naps. Different actigraphy settings may be optimal depending upon the variables of interest. Discrimination of sleep and wake during periods of waking quiescence is not as robust as during periods of mainly daytime sleep.

A Retrospective Examination of Sleep Disturbance across the Course of Bipolar Disorder.

Background Sleep disturbance is a prevalent and clinically significant feature of bipolar disorder. However, there are aspects of sleep and bipolar disorder that have been minimally characterized. This study aims to fill several gaps in the literature by examining the prevalence, coexistence, and persistence of sleep disturbance retrospectively across a five-year period in bipolar disorder. Methods Fifty-one people with bipolar disorder I and comorbid insomnia who were currently inter-episode completed the NIMH Retrospective Life-Charting Methodology (the life chart). The life chart was used to document the prevalence, coexistence, and persistence of insomnia, hypersomnia, delayed sleep phase, reduced sleep need, and irregular sleep patterns across the course of five years. Results Across the five year period, manic months were primarily characterized by reduced sleep need (62.8%) and insomnia (38.1%), depressive months by hypersomnia (56.0%) and insomnia (51.9%), mixed months by all five types of sleep disturbance, and inter-episode months by insomnia (67.4%). There was coexistence in the types of sleep disturbance experienced. Further, each type of sleep disturbance demonstrated persistence across the five years, with persistence rates being the highest for insomnia (49.0–58.8%). Conclusions Sleep disturbance is a prevalent and complex feature across mood episodes and inter-episode periods of bipolar disorder. Further, there is variation in the types of sleep disturbance experienced.

The Association Between Insomnia-related Sleep Disruptions and Cognitive Dysfunction during the Inter-episode Phase of Bipolar Disorder

Sleep disturbance and cognitive dysfunction are two domains of impairment during inter-episode bipolar disorder. Despite evidence demonstrating the importance of sleep for cognition in healthy and sleep-disordered samples, this link has been minimally examined in bipolar disorder. The present study tested the association between insomnia-related sleep disruptions and cognitive dysfunction during inter-episode bipolar disorder. Forty-seven participants with bipolar disorder and a comorbid insomnia diagnosis (BD-Insomnia) and 19 participants with bipolar disorder without sleep disturbance in the last six months (BD-Control) participated in the study. Two domains of cognition were assessed: working memory and verbal learning. Insomnia-related sleep disruptions were assessed both categorically (i.e., insomnia diagnosis) and dimensionally (i.e., total wake time, total sleep time, total wake time variability, and total sleep time variability). Hierarchical linear regressions, adjusting for participant age, demonstrated that insomnia diagnosis did not have an independent or interactive effect on cognition. However, regardless of insomnia diagnosis, greater total sleep time variability predicted poorer working memory and verbal learning performance. Further, following sleep treatment, a reduction in total wake time predicted improved working memory performance and a reduction in total sleep time variability predicted improved verbal learning performance. These findings raise the possibility that sleep disturbance may contribute to cognitive dysfunction in bipolar disorder and highlight the importance of treating sleep disturbance in bipolar disorder.

Development and Validation of the Sleep Inertia Questionnaire (SIQ) and Assessment of Sleep Inertia in Analogue and Clinical Depression

Sleep inertia is the transitional state from sleep to wake. Research on sleep inertia is important in depression because many people with depression report having difficulty getting out of bed, which contributes to impairment and can impede the implementation of interventions. The first aim was to develop and validate the first self-report measure of sleep inertia, the Sleep Inertia Questionnaire (SIQ). The second aim was to compare reports of sleep inertia across three groups: (1) No-to-Mild-Depression, (2) Analogue-Depression, and (3) Syndromal-Depression. The SIQ demonstrates strong psychometric properties; it has good to excellent internal consistency, strong construct validity, and SIQ severity is associated with less prior sleep duration. Sleep inertia is more severe in the Analogue-Depression and Syndromal-Depression Groups compared to the No-to-Mild-Depression Group. In conclusion, the SIQ is a reliable measure of sleep inertia and has potential for improving the assessment of sleep inertia in clinical and research settings.

Cognitive Therapy for Insomnia

Cognitive therapy for insomnia (CT-I) is based on a cognitive model that posits that the processes maintaining insomnia can include (1) worry and rumination, (2) attentional bias and monitoring for sleep-related threat, (3) unhelpful beliefs about sleep, (4) misperception of sleep and daytime deficits, and (5) safety behaviors that maintain unhelpful beliefs. The aim of CT-I is to reverse all five maintaining processes during the night as well as the day. Promising new directions in CT-I, such as training in savoring and positive thinking, altering expectations about sleep, targeting daytime cognitive processes, and developing mindfulness and acceptance, are also discussed.