Total sleep time and kynurenine metabolism associated with mood symptom severity in bipolar disorder

Abstract Introduction Seasonal affective disorder (SAD) increases risk for attention-deficit/hyperactivity disorder (ADHD), although the mechanism linking SAD and ADHD is unknown. Prior research has identified insomnia and delayed sleep phase in both ADHD and SAD. We hypothesized that sleep duration and timing in SAD would be associated with the severity of ADHD symptoms. Methods Adults with SAD (n = 45) and subsyndromal SAD (S-SAD; n = 18) aged 19-66 years from Pittsburgh, PA., were assessed for ADHD symptoms, self-report sleep quality, depression severity, and daytime sleepiness in the Winter. Participants wore an Actiwatch for 4-14 days, from which we calculated sleep-onset latency, total sleep time, sleep midpoint, and sleep efficiency. We conducted a hierarchical multivariate linear regression to determine if sleep characteristics predict ADHD symptom severity in our sample while controlling for depressive symptoms. Age and gender were added in Step 1, seasonal depression severity in Step 2, actigraphy-based total sleep time, sleep onset latency, midpoint, and efficiency in Step 3, and self-reported sleep quality and daytime sleepiness in Step 4. Results Participants mostly scored in the “likely” or “highly likely” ADHD range (87.30%, n=55), higher than the national prevalence rate (4.4%). When controlling for age, gender, and depression severity, only shorter actigraphy-based total sleep time was associated with higher ADHD symptom severity (β=-0.30, p<0.05). However, when self-reported sleep quality and daytime sleepiness were added as predictors, total sleep time was no longer a statistically-significant predictor of ADHD symptom severity and only daytime sleepiness predicted ADHD symptom severity (β=0.31, p<0.05). Conclusion Our results suggest that individuals with SAD who experience daytime sleepiness and/or possibly shorter actigraphy-based sleep duration experience higher ADHD symptom severity. Treatments like Trans-C or CBT-I to improve daytime sleepiness and sleep duration may be indicated for SAD patients who present with comorbid ADHD symptoms. Support NIMH K.A.R. MH103303

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Sleep and Circadian Rhythm Disturbance in Remitted Schizophrenia and Bipolar Disorder: A Systematic Review and Meta-analysis

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa024 ◽

2020 ◽

Vol 46 (5) ◽

pp. 1126-1143 ◽

Cited By ~ 4

Author(s):

Nicholas Meyer ◽

Sophie M Faulkner ◽

Robert A McCutcheon ◽

Toby Pillinger ◽

Derk-Jan Dijk ◽

...

Keyword(s):

Bipolar Disorder ◽

Circadian Rhythm ◽

Motor Activity ◽

Sleep Latency ◽

Total Sleep Time ◽

Sleep Time ◽

Mean Difference ◽

Effect Sizes ◽

Time In Bed ◽

Modifiable Factors

Abstract Background Sleep and circadian rhythm disturbances in schizophrenia are common, but incompletely characterized. We aimed to describe and compare the magnitude and heterogeneity of sleep-circadian alterations in remitted schizophrenia and compare them with those in interepisode bipolar disorder. Methods EMBASE, Medline, and PsycINFO were searched for case–control studies reporting actigraphic parameters in remitted schizophrenia or bipolar disorder. Standardized and absolute mean differences between patients and controls were quantified using Hedges’ g, and patient–control differences in variability were quantified using the mean-scaled coefficient of variation ratio (CVR). A wald-type test compared effect sizes between disorders. Results Thirty studies reporting on 967 patients and 803 controls were included. Compared with controls, both schizophrenia and bipolar groups had significantly longer total sleep time (mean difference [minutes] [95% confidence interval {CI}] = 99.9 [66.8, 133.1] and 31.1 [19.3, 42.9], respectively), time in bed (mean difference = 77.8 [13.7, 142.0] and 50.3 [20.3, 80.3]), but also greater sleep latency (16.5 [6.1, 27.0] and 2.6 [0.5, 4.6]) and reduced motor activity (standardized mean difference [95% CI] = −0.86 [−1.22, −0.51] and −0.75 [−1.20, −0.29]). Effect sizes were significantly greater in schizophrenia compared with the bipolar disorder group for total sleep time, sleep latency, and wake after sleep onset. CVR was significantly elevated in both diagnoses for total sleep time, time in bed, and relative amplitude. Conclusions In both disorders, longer overall sleep duration, but also disturbed initiation, continuity, and reduced motor activity were found. Common, modifiable factors may be associated with these sleep-circadian phenotypes and advocate for further development of transdiagnostic interventions that target them.

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White blood cell count correlates with mood symptom severity and specific mood symptoms in bipolar disorder

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867416644508 ◽

2016 ◽

Vol 51 (4) ◽

pp. 355-365 ◽

Cited By ~ 13

Author(s):

Ole Köhler ◽

Louisa G Sylvia ◽

Charles L Bowden ◽

Joseph R Calabrese ◽

Michael Thase ◽

...

Keyword(s):

Bipolar Disorder ◽

Confidence Interval ◽

Blood Cell ◽

Cell Count ◽

White Blood Cell Count ◽

White Blood Cell ◽

Symptom Severity ◽

Rating Scale ◽

Blood Cell Count ◽

Mood Symptom

Objective: Immune alterations may play a role in bipolar disorder etiology; however, the relationship between overall immune system functioning and mood symptom severity is unknown. Methods: The two comparative effectiveness trials, the Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder Study (Bipolar CHOICE) and the Lithium Treatment Moderate-Dose Use Study (LiTMUS), were similar trials among patients with bipolar disorder. At study entry, white blood cell count and bipolar mood symptom severity (via Montgomery-Aasberg Depression Rating Scale and Bipolar Inventory of Symptoms Scale) were assessed. We performed analysis of variance and linear regression analyses to investigate relationships between deviations from median white blood cell and multinomial regression analysis between higher and lower white blood cell levels. All analyses were adjusted for age, gender, body mass index, smoking, diabetes, hypertension and hyperlipidemia. Results: Among 482 Bipolar CHOICE participants, for each 1.0 × 109/L white blood cell deviation, the overall Bipolar Inventory of Symptoms Scale severity increased significantly among men (coefficient = 2.13; 95% confidence interval = [0.46, −3.79]; p = 0.013), but not among women (coefficient = 0.87; 95% confidence interval = [−0.87, −2.61]; p = 0.33). Interaction analyses showed a trend toward greater Bipolar Inventory of Symptoms Scale symptom severity among men (coefficient = 1.51; 95% confidence interval = [−0.81, −3.82]; p = 0.2). Among 283 LiTMUS participants, higher deviation from the median white blood cell showed a trend toward higher Montgomery-Aasberg Depression Rating Scale scores among men (coefficient = 1.33; 95% confidence interval = [−0.22, −2.89]; p = 0.09), but not among women (coefficient = 0.34; 95% confidence interval = [−0.64, −1.32]; p = 0.50). When combining LiTMUS and Bipolar CHOICE, Montgomery-Aasberg Depression Rating Scale scores increased significantly among men (coefficient = 1.09; 95% confidence interval = [0.31, −1.87]; p = 0.006) for each 1.0 × 109/L white blood cell deviation, whereas we found a weak association among women (coefficient = 0.55; 95% confidence interval = [−0.20, −1.29]; p = 0.14). Lower and higher white blood cell levels correlated with greater symptom severity and specific symptoms, varying according to gender. Conclusion: Deviations in an overall immune system marker, even within the normal white blood cell range, correlated with mood symptom severity in bipolar disorder, mostly among males. Studies are warranted investigating whether white blood cell count may predict response to mood-stabilizing treatment.

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Finding a Composite Measure for Data From Wrist Actigraphy in Bipolar Disorder

Innovation in Aging ◽

10.1093/geroni/igab046.1306 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 338-339

Author(s):

Ellen Lee ◽

David Wing ◽

Sonia Ancoli-Israel ◽

Colin Depp ◽

Ho-Kyoung Yoon ◽

...

Keyword(s):

Bipolar Disorder ◽

Total Sleep Time ◽

Sleep Onset ◽

Sleep Time ◽

Composite Measure ◽

Subjective Sleep ◽

Wrist Actigraphy ◽

Z Scores ◽

Participant Characteristics ◽

Composite Scores

Abstract Actigraphy can objectively measure sleep in studies on Bipolar Disorder (BD) where subjective sleep ratings might be influenced by affect. Actigraphy data are complex necessitating data reduction approaches. We created a composite score of actigraphy sleep metrics (total sleep time [TST], wake after sleep onset [WASO], and percent sleep [PS]) in BD. We computed z-scores of sleep measures for n=51 BD vs. n=80 healthy subjects and averaged scores. We examined associations with participant characteristics and used LASSO to identify metrics best explaining composite variability. Higher composite scores (better sleep) were seen in employed vs. unemployed (t=2.40, df=34, p=0.02), and correlated with higher medication load (r=0.41, p=0.004), lower mania symptomatology (r=-0.33, p=0.04) and lower interleukin (IL)-6 levels (r=-0.32, p=0.02). TST best explained variability in medication load and PS best explained employment, mania symptoms and IL-6. Given observed specificity of associations, selecting theory-driven sleep metrics may be more appropriate than a composite.

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Misperception of sleep in bipolar disorder: an exploratory study using questionnaire versus actigraphy

International Journal of Bipolar Disorders ◽

10.1186/s40345-020-00198-x ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Henrik Myhre Ihler ◽

Manon Meyrel ◽

Vincent Hennion ◽

Julia Maruani ◽

Gregory Gross ◽

...

Keyword(s):

Bipolar Disorder ◽

Obstructive Sleep Apnea ◽

Sleep Latency ◽

Total Sleep Time ◽

Sleep Time ◽

Sleep Efficiency ◽

Objective Measures ◽

Obstructive Sleep

Abstract Background The concept of misperception of sleep refers to the estimated discrepancy between subjective and objective measures of sleep. This has been assessed only in a few prior studies in individuals with Bipolar Disorder (BD) as compared to Healthy Controls (HC) and with mixed results. Methods We assessed a sample of 133 euthymic individuals with BD and 63 HC for retrospective subjective (Pittsburgh Sleep Quality Index) and objective (21 days of actigraphy recording) measures of total sleep time, sleep latency and sleep efficiency. We first investigated the correlations between these subjective and objective measures in the two groups. We then compared individuals with BD and HC for the absolute values of the differences between subjective and objective sleep parameters, used as a proxy of the magnitude of misperception of sleep. Finally, we undertook regression analyses to assess associations between clinical groups, core demographics, clinical factors and misperception of sleep. Results The correlation coefficients between subjective and objective measures of sleep did not differ between groups (total sleep time: rho = .539 in BD and rho = .584 in HC; sleep latency: rho = .190 in BD and rho = .125 in HC; sleep efficiency: rho = .166 in BD and rho = .222 in HC). Individuals with BD did not differ from HC in the magnitude of misperception of total sleep time, sleep latency nor sleep efficiency. Individuals with BD type 1 misperceived their sleep efficiency significantly more than individuals with BD type 2, with no further difference between BD type 1 and BD type 2 regarding sleep latency and sleep duration misperceptions. Three factors (age, symptoms of obstructive sleep apnea, and mild depressive symptoms), were the main contributors to the magnitude of misperception of sleep. Conclusions Misperception of sleep was not associated with a diagnosis of BD. In this sample, mild depressive symptoms, older age, or symptoms of obstructive sleep apnea may be related to greater sleep misperception. In that case, the reliability of subjective measures may decrease as the misperception of sleep increases. This study may help guide clinicians in selecting the best approach for assessing sleep (objective versus subjective measures) in individuals with BD.

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Association of functioning and quality of life with objective and subjective measures of sleep and biological rhythms in major depressive and bipolar disorder

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867419829228 ◽

2019 ◽

Vol 53 (7) ◽

pp. 683-696 ◽

Cited By ~ 4

Author(s):

Anastasiya Slyepchenko ◽

Olivia R Allega ◽

Xiamin Leng ◽

Luciano Minuzzi ◽

Maha M Eltayebani ◽

...

Keyword(s):

Quality Of Life ◽

Bipolar Disorder ◽

Sleep Quality ◽

Mood Disorders ◽

Total Sleep Time ◽

Light Exposure ◽

Biological Rhythms ◽

Sleep Time ◽

Major Depressive

Objective: Disruptions in biological rhythms and sleep are a core aspect of mood disorders, with sleep and rhythm changes frequently occurring prior to and during mood episodes. Wrist-worn actigraphs are increasingly utilized to measure ambulatory activity rhythm and sleep patterns. Methods: A comprehensive study using subjective and objective measures of sleep and biological rhythms was conducted in 111 participants (40 healthy volunteers [HC], 38 with major depressive disorder [MDD] and 33 with bipolar disorder [BD]). Participants completed 15-day actigraphy and first-morning urine samples to measure 6-sulfatoxymelatonin levels. Sleep and biological rhythm questionnaires were administered: Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), Munich Chronotype Questionnaire (MCTQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Actigraph data were analyzed for sleep and daily activity rhythms, light exposure and likelihood of transitioning between rest and activity states. Results: Mood groups had worse subjective sleep quality (PSQI) and biological rhythm disruption (BRIAN) and higher objective mean nighttime activity than controls. Participants with BD had longer total sleep time, higher circadian quotient and lower 6-sulfatoxymelatonin levels than HC group. The MDD group had longer sleep onset latency and higher daytime probability of transitioning from rest to activity than HCs. Mood groups displayed later mean timing of light exposure. Multiple linear regression analysis with BRIAN scores, circadian quotient, mean nighttime activity during rest and daytime probability of transitioning from activity to rest explained 43% of variance in quality-of-life scores. BRIAN scores, total sleep time and probability of transitioning from activity to rest explained 52% of variance in functioning (all p < 0.05). Conclusions: Disruption in biological rhythms is associated with poorer functioning and quality of life in bipolar and MDD. Investigating biological rhythms and sleep using actigraphy variables, urinary 6-sulfatoxymelatonin and subjective measures provide evidence of widespread sleep and circadian system disruptions in mood disorders.

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Evaluating Sleep Characteristics in Intensive Care Unit and Non-Intensive Care Unit Physicians

Anaesthesia and Intensive Care ◽

10.1177/0310057x1103900614 ◽

2011 ◽

Vol 39 (6) ◽

pp. 1071-1075 ◽

Cited By ~ 3

Author(s):

G. Ok ◽

H. Yilmaz ◽

D. Tok ◽

K. Erbüyün ◽

S. Çoban ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Shift Work ◽

Pittsburgh Sleep Quality Index ◽

Sleep Latency ◽

Total Sleep Time ◽

Total Activity ◽

Sleep Time ◽

Sleep Parameters ◽

Icu Physicians

Healthcare workers’ cognitive performances and alertness are highly vulnerable to sleep loss and circadian rhythms. The purpose of this study was to investigate the changes in sleep characteristics of intensive care unit (ICU) and non-ICU physicians. Actigraphic sleep parameters, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Hamilton Depression Rating Scale were evaluated for ICU and non-ICU physicians on the day before shift-work and on three consecutive days after shift-work. Total sleep time, sleep latency, wakefulness after sleep onset, total activity score, movement fragmentation index, sleep efficiency, daytime naps and total nap duration were also calculated by actigraph. In the ICU physicians, the mean Pittsburgh Sleep Quality Index score was significantly higher than the non-ICU physicians (P=0.001), however mean Epworth Sleepiness Scale scores were not found significantly different between the two groups. None of the scores for objective sleep parameters were statistically different between the groups when evaluated before and after shift-work (P >0.05). However in both ICU and non-ICU physicians, sleep latency was observed to be decreased within the three consecutive-day period after shift-work with respect to basal values (P <0.001). Total sleep time, total activity score and sleep efficiency scores prior to shift-work were significantly different from shift-work and the three consecutive-days after shift-work, in both groups. Working in the ICU does not have an impact on objective sleep characteristics of physicians in this study. Large cohort studies are required to determine long-term health concerns of shift-working physicians.

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Tasimelteon safely and effectively improves sleep in Smith–Magenis syndrome: a double-blind randomized trial followed by an open-label extension

Genetics in Medicine ◽

10.1038/s41436-021-01282-y ◽

2021 ◽

Author(s):

Christos M. Polymeropoulos ◽

Justin Brooks ◽

Emily L. Czeisler ◽

Michaela A. Fisher ◽

Mary M. Gibson ◽

...

Keyword(s):

Sleep Quality ◽

Crossover Study ◽

Total Sleep Time ◽

Sleep Time ◽

Open Label ◽

Double Blind ◽

Open Label Study ◽

Label Study ◽

Sleep Complaints ◽

Open Label Extension

Abstract Purpose To assess the efficacy of tasimelteon to improve sleep in Smith–Magenis syndrome (SMS). Methods A 9-week, double-blind, randomized, two-period crossover study was conducted at four US clinical centers. Genetically confirmed patients with SMS, aged 3 to 39, with sleep complaints participated in the study. Patients were assigned to treatment with tasimelteon or placebo in a 4-week crossover study with a 1-week washout between treatments. Eligible patients participated in an open-label study and were followed for >3 months. Results Improvement of sleep quality (DDSQ50) and total sleep time (DDTST50) on the worst 50% of nights were primary endpoints. Secondary measures included actigraphy and behavioral parameters. Over three years, 52 patients were screened, and 25 patients completed the randomized portion of the study. DDSQ50 significantly improved over placebo (0.4, p = 0.0139), and DDTST50 also improved (18.5 minutes, p = 0.0556). Average sleep quality (0.3, p = 0.0155) and actigraphy-based total sleep time (21.1 minutes, p = 0.0134) improved significantly, consistent with the primary outcomes. Patients treated for ≥90 days in the open-label study showed persistent efficacy. Adverse events were similar between placebo and tasimelteon. Conclusion Tasimelteon safely and effectively improved sleep in SMS.

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Gender differences in BaYaka forager sleep-wake patterns in forest and village contexts

Scientific Reports ◽

10.1038/s41598-021-92816-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Erica Kilius ◽

David R. Samson ◽

Sheina Lew-Levy ◽

Mallika S. Sarma ◽

Ujas A. Patel ◽

...

Keyword(s):

Sleep Quality ◽

Total Sleep Time ◽

Sleep Time ◽

Small Scale ◽

Cultural Variation ◽

Sleep Patterns ◽

Economic Activities ◽

Mixed Effect ◽

Wake Patterns ◽

The Republic

AbstractSleep studies in small-scale subsistence societies have broadened our understanding of cross-cultural sleep patterns, revealing the flexibility of human sleep. We examined sleep biology among BaYaka foragers from the Republic of Congo who move between environmentally similar but socio-ecologically distinct locations to access seasonal resources. We analyzed the sleep–wake patterns of 51 individuals as they resided in a village location (n = 39) and a forest camp (n = 23) (362 nights total). Overall, BaYaka exhibited high sleep fragmentation (50.5) and short total sleep time (5.94 h), suggestive of segmented sleep patterns. Sleep duration did not differ between locations, although poorer sleep quality was exhibited in the village. Linear mixed effect models demonstrated that women’s sleep differed significantly from men’s in the forest, with longer total sleep time (β ± SE = − 0.22 ± 0.09, confidence interval (CI) = [− 0.4, − 0.03]), and higher sleep quality (efficiency; β ± SE = − 0.24 ± 0.09, CI = [− 0.42, − 0.05]). These findings may be due to gender-specific social and economic activities. Circadian rhythms were consistent between locations, with women exhibiting stronger circadian stability. We highlight the importance of considering intra-cultural variation in sleep–wake patterns when taking sleep research into the field.

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The feasibility and reliability of actigraphy to monitor sleep in intensive care patients: an observational study

Critical Care ◽

10.1186/s13054-020-03447-8 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

L. J. Delaney ◽

E. Litton ◽

K. L. Melehan ◽

H.-C. C. Huang ◽

V. Lopez ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Observational Study ◽

Total Sleep Time ◽

Sleep Time ◽

Moderate Level ◽

Sleep Monitoring ◽

Clinical Trial Registration ◽

Wake Time ◽

Intensive Care Patients

Abstract Background Sleep amongst intensive care patients is reduced and highly fragmented which may adversely impact on recovery. The current challenge for Intensive Care clinicians is identifying feasible and accurate assessments of sleep that can be widely implemented. The objective of this study was to investigate the feasibility and reliability of a minimally invasive sleep monitoring technique compared to the gold standard, polysomnography, for sleep monitoring. Methods Prospective observational study employing a within subject design in adult patients admitted to an Intensive Care Unit. Sleep monitoring was undertaken amongst minimally sedated patients via concurrent polysomnography and actigraphy monitoring over a 24-h duration to assess agreement between the two methods; total sleep time and wake time. Results We recruited 80 patients who were mechanically ventilated (24%) and non-ventilated (76%) within the intensive care unit. Sleep was found to be highly fragmented, composed of numerous sleep bouts and characterized by abnormal sleep architecture. Actigraphy was found to have a moderate level of overall agreement in identifying sleep and wake states with polysomnography (69.4%; K = 0.386, p < 0.05) in an epoch by epoch analysis, with a moderate level of sensitivity (65.5%) and specificity (76.1%). Monitoring accuracy via actigraphy was improved amongst non-ventilated patients (specificity 83.7%; sensitivity 56.7%). Actigraphy was found to have a moderate correlation with polysomnography reported total sleep time (r = 0.359, p < 0.05) and wakefulness (r = 0.371, p < 0.05). Bland–Altman plots indicated that sleep was underestimated by actigraphy, with wakeful states overestimated. Conclusions Actigraphy was easy and safe to use, provided moderate level of agreement with polysomnography in distinguishing between sleep and wakeful states, and may be a reasonable alternative to measure sleep in intensive care patients. Clinical Trial Registration number ACTRN12615000945527 (Registered 9/9/2015).

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