Sleep disturbances in ADHD: investigating the contribution of polygenic liability for ADHD and sleep-related phenotypes.

Sleep disturbances are common in attention deficit hyperactivity disorder (ADHD) and associated with poor outcomes. We tested whether, in children with ADHD, (1) polygenic liability for sleep phenotypes is over- or under-transmitted from parents, (2) this liability is linked to comorbid sleep disturbances, and (3) ADHD genetic risk is associated with comorbid sleep disturbances. We derived polygenic scores (PGS) for insomnia, chronotype, sleep duration, and ADHD, in 758 children (5-18 years old) diagnosed with ADHD and their parents. We conducted polygenic transmission disequilibrium tests for each sleep PGS in complete parent-offspring ADHD trios (N = 328) and an independent replication sample of ADHD trios (N = 844). Next, we tested whether insomnia, sleep duration, and ADHD PGS were associated with co-occurring sleep phenotypes (hypersomnia, insomnia, restless sleep, poor sleep quality, and nightmares) in children with ADHD. Children's insomnia and chronotype PGS did not differ from mid-parent average PGS but long sleep duration PGS were significantly over-transmitted to children with ADHD. This was supported by a combined analysis using the replication sample. Insomnia, sleep duration, and ADHD PGS were not associated with comorbid sleep disturbances. There is weak evidence that children with ADHD over-inherit polygenic liability for longer sleep duration and do not differentially inherit polygenic liability for insomnia or chronotype. There was insufficient evidence that childhood sleep disturbances were driven by polygenic liability for ADHD or sleep traits, suggesting that sleep disturbances in ADHD may be aetiologically different to general population sleep phenotypes and do not index greater ADHD genetic risk burden.

Mental health prior to and during the COVID-19 pandemic in individuals with bipolar disorder: Insights from prospective longitudinal data.

OBJECTIVES: Many studies have examined the impact of COVID-19 on the mental health of the public, but few have focused on individuals with existing severe mental illness with longitudinal data before and during the pandemic. AIMS: To investigate the impact of the COVID-19 pandemic on the mental health of people with bipolar disorder (BD). METHODS: In an ongoing study of people with BD who used an online mood monitoring tool, True Colours, 356 participants provided weekly data on their mental health. Symptoms of depression, mania, insomnia, and suicidal thoughts were compared in 2019 and 2020. From May 2020, participants also provided weekly data on the effect of the COVID-19 pandemic on anxiety, coping strategies, access to care, and medications. RESULTS: On average, symptoms of depression, mania, insomnia, and suicidal thoughts did not significantly differ in 2020 compared to 2019, but there was evidence of heterogeneity. There were high rates of anxiety about the pandemic and its impact on coping strategies, which increased to over 70% of responders in January 2021. A significant proportion of participants reported difficulty accessing routine care (27%) and medications (21%). CONCLUSIONS: Although mood symptoms did not significantly increase during the pandemic overall, we observed heterogeneity among our BD sample and other impacted areas. Individuals' unique histories and psychosocial circumstances are key and should be explored in future qualitative studies. The significant impacts of the pandemic may take time to manifest, particularly among those who are socioeconomically disadvantaged, highlighting the need for further long-term prospective studies.

Patterns and clinical correlates of lifetime alcohol consumption in women and men with bipolar disorder: Findings from the UK Bipolar Disorder Research Network.

OBJECTIVES: Despite previous literature on comorbid alcohol use disorders (AUDs) in bipolar disorder (BD), little is known about patterns of alcohol use more widely in this population. We have examined lifetime heaviest average weekly alcohol consumption levels in a large well-characterised UK sample including lifetime clinical correlates of increasing levels of alcohol use. METHODS: Participants were 1203 women and 673 men with bipolar I disorder interviewed by semi-structured interview who had consumed alcohol regularly at any point in their life. RESULTS: Over half of both women (52.3%) and men (73.6%) had regularly consumed over double the current UK recommended guideline for alcohol consumption. In women and men increasing levels of lifetime alcohol consumption were significantly associated with the presence of suicide attempts (women: OR 1.82, P < .001; men: OR 1.48, P = .005) and rapid cycling (women: OR 1.89, P < .001; men: OR 1.88, P < .001). In women only, increasing levels of alcohol consumption were significantly associated with more episodes of depression (OR 1.35, P < .001) and mania (OR 1.30, P < .004) per illness year, less impairment in functioning during the worst episode of mania (OR 1.02, P < .001), fewer psychiatric admissions (OR 0.51, P < .001), comorbid panic disorder (OR 2.16, P < .001) and eating disorder (OR 2.37, P < .001). CONCLUSIONS: Our results highlight the clinical importance of obtaining detailed information on levels of alcohol consumption among patients with BD. Increased levels of alcohol use, not necessarily reaching criteria for AUD, may be helpful in predicting BD illness course, in particular eating disorders comorbidity in women.

Is sleep disruption a trigger for postpartum psychosis?

An episode of postpartum psychosis can be devastating for a woman and her family, and it is vital we understand the factors involved in the aetiology of this condition. Sleep and circadian rhythm disruption is a plausible candidate but further research is needed that builds on the latest advances in chronobiology and neuroscience.

Investigating Direct and Indirect Genetic Effects in Attention-Deficit/Hyperactivity Disorder Using Parent-Offspring Trios.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is highly heritable, but little is known about the relative effects of transmitted (i.e., direct) and nontransmitted (i.e., indirect) common variant risks. Using parent-offspring trios, we tested whether polygenic liability for neurodevelopmental and psychiatric disorders and lower cognitive ability is overtransmitted to ADHD probands. We also tested for indirect or genetic nurture effects by examining whether nontransmitted ADHD polygenic liability is elevated. Finally, we examined whether complete trios are representative of the clinical ADHD population. METHODS: Polygenic risk scores (PRSs) for ADHD, anxiety, autism, bipolar disorder, depression, obsessive-compulsive disorder, schizophrenia, Tourette syndrome, and cognitive ability were calculated in UK control subjects (n = 5081), UK probands with ADHD (n = 857), their biological parents (n = 328 trios), and also a replication sample of 844 ADHD trios. RESULTS: ADHD PRSs were overtransmitted and cognitive ability and obsessive-compulsive disorder PRSs were undertransmitted. These results were independently replicated. Overtransmission of polygenic liability was not observed for other disorders. Nontransmitted alleles were not enriched for ADHD liability compared with control subjects. Probands from incomplete trios had more hyperactive-impulsive and conduct disorder symptoms, lower IQ, and lower socioeconomic status than complete trios. PRS did not vary by trio status. CONCLUSIONS: The results support direct transmission of polygenic liability for ADHD and cognitive ability from parents to offspring, but not for other neurodevelopmental/psychiatric disorders. They also suggest that nontransmitted neurodevelopmental/psychiatric parental alleles do not contribute indirectly to ADHD via genetic nurture. Furthermore, ascertainment of complete ADHD trios may be nonrandom, in terms of demographic and clinical factors.

Associations between comorbid anxiety and sleep disturbance in people with bipolar disorder: Findings from actigraphy and subjective sleep measures.

BACKGROUND: Studies show that comorbid anxiety disorders are common in people with bipolar disorder. However, little is known about whether this anxiety is associated with sleep disturbance. We investigated, in individuals with bipolar disorder, whether comorbid anxiety disorder is associated with sleep disturbance. METHODS: Participants were 101 (64% female) currently euthymic individuals with a history of bipolar disorder. Sleep disturbances were assessed using self-report measures of sleep quality (Pittsburgh Sleep Quality Index, PSQI) and six weeks of sleep monitoring using actigraphy. Bipolar disorder and comorbid anxiety diagnoses were assessed using the Mini International Neuropsychiatric Interview. Multiple regression analyses examined associations between comorbid anxiety and sleep disturbance, whilst controlling for confounding covariates known to impact on sleep. RESULTS: A comorbid anxiety disorder was associated with increased sleep disturbance as measured using the PSQI global score (B = 3.58, 95% CI 1.85-5.32, P < 0.001) but was not associated with sleep metrics (total sleep time, sleep onset latency, sleep efficiency, and wake after sleep onset) derived using actigraphy. LIMITATIONS: Objective measures of sleep were limited to actigraphy, therefore we were not able to examine differences in sleep neurophysiology. CONCLUSIONS: Clinicians should be aware that comorbid anxiety may increase the risk of experiencing subjective sleep disturbance in people with bipolar disorder. Research should assess for evidence of comorbid anxiety when examining associations between sleep and bipolar disorder. Future research should explore the mechanisms by which comorbid anxiety may contribute to subjective sleep disturbances in bipolar disorder using neurophysiological measures of sleep (i.e., polysomnography).

The effect of the COVID-19 pandemic on mental health in individuals with pre-existing mental illness.

BACKGROUND: There is evidence that the COVID-19 pandemic has negatively affected mental health, but most studies have been conducted in the general population. AIMS: To identify factors associated with mental health during the COVID-19 pandemic in individuals with pre-existing mental illness. METHOD: Participants (N = 2869, 78% women, ages 18-94 years) from a UK cohort (the National Centre for Mental Health) with a history of mental illness completed a cross-sectional online survey in June to August 2020. Mental health assessments were the GAD-7 (anxiety), PHQ-9 (depression) and WHO-5 (well-being) questionnaires, and a self-report question on whether their mental health had changed during the pandemic. Regressions examined associations between mental health outcomes and hypothesised risk factors. Secondary analyses examined associations between specific mental health diagnoses and mental health. RESULTS: A total of 60% of participants reported that mental health had worsened during the pandemic. Younger age, difficulty accessing mental health services, low income, income affected by COVID-19, worry about COVID-19, reduced sleep and increased alcohol/drug use were associated with increased depression and anxiety symptoms and reduced well-being. Feeling socially supported by friends/family/services was associated with better mental health and well-being. Participants with a history of anxiety, depression, post-traumatic stress disorder or eating disorder were more likely to report that mental health had worsened during the pandemic than individuals without a history of these diagnoses. CONCLUSIONS: We identified factors associated with worse mental health during the COVID-19 pandemic in individuals with pre-existing mental illness, in addition to specific groups potentially at elevated risk of poor mental health during the pandemic.

Integrating visual mental images and visual percepts: new evidence for depictive representations.

In two experiments, we used a temporal integration task to investigate visual mental images based on information in short-term memory or generated from information stored in long-term memory (LTM). We specifically asked whether the two sorts of images rely on depictive representations. If mental images rely on depictive representations, then it should be possible to combine mental images and visual percepts into a single representation that preserves the spatial layout of the display. To demonstrate this, participants were asked to generate mental images and then combine them with visual percepts of grids that were partially filled with different numbers of dots. Participants were asked to determine which cell remained empty when the two grids were combined. We contrasted predictions of propositional or verbal description theories with those of depictive theories, and report findings that support the claim that mental images-based on either short-term or LTM-depict information.

Heritability of Sleep and Its Disorders in Childhood and Adolescence.

PURPOSE OF REVIEW: This review summarizes recent literature on the heritability of sleep and sleep disorders in childhood and adolescence. We also identify gaps in the literature and priorities for future research. RECENT FINDINGS: Findings indicate that age, measurement method, reporter, and timing of sleep measurements can influence heritability estimates. Recent genome-wide association studies (GWAS) have identified differences in the heritability of sleep problems when ancestral differences are considered, but sample sizes are small compared to adult GWAS. Most studies focus on sleep variables in the full range rather than on disorder. Studies using objective measures of sleep typically comprised small samples. SUMMARY: Current evidence demonstrates a wide range of heritability estimates across sleep phenotypes in childhood and adolescence, but research in larger samples, particularly using objective sleep measures and GWAS, is needed. Further understanding of environmental mechanisms and the interaction between genes and environment is key for future research.

Comparison of Genetic Liability for Sleep Traits Among Individuals With Bipolar Disorder I or II and Control Participants.

Importance: Insomnia, hypersomnia, and an evening chronotype are common in individuals with bipolar disorder (BD), but whether this reflects shared genetic liability is unclear. Stratifying by BD subtypes could elucidate this association and inform sleep and BD research. Objective: To assess whether polygenic risk scores (PRSs) for sleep traits are associated with BD subtypes I and II. Design, Setting, and Participants: This case-control study was conducted in the United Kingdom and Sweden with participants with BD and control participants. Multinomial regression was used to assess whether PRSs for insomnia, daytime sleepiness, sleep duration, and chronotype are associated with BD subtypes compared with control participants. Affected individuals were recruited from the Bipolar Disorder Research Network. Control participants were recruited from the 1958 British Birth Cohort and the UK Blood Service. Analyses were repeated in an independent Swedish sample from August 2018 to July 2019. All participants were of European ancestry. Exposures: Standardized PRSs derived using alleles from genome-wide association studies of insomnia, sleep duration, daytime sleepiness, and chronotype. These were adjusted for the first 10 population principal components, genotyping platforms, and sex. Main Outcomes and Measures: Association of PRSs with BD subtypes, determined by semistructured psychiatric interview and case notes. Results: The main analysis included 4672 participants with BD (3132 female participants [67.0%]; 3404 with BD-I [72.9%]) and 5714 control participants (2812 female participants [49.2%]). Insomnia PRS was associated with increased risk of BD-II (relative risk [RR], 1.14 [95% CI, 1.07-1.21]; P = 8.26 × 10-5) but not BD-I (RR, 0.98 [95% CI, 0.94-1.03]; P = .409) relative to control participants. Sleep-duration PRS was associated with BD-I (RR, 1.10 [95% CI, 1.06-1.15]; P = 1.13 × 10-5) but not BD-II (RR, 0.99 [95% CI, 0.93-1.06]; P = .818). Associations between (1) insomnia PRS and BD-II and (2) sleep-duration PRS and BD-I were replicated in the Swedish sample of 4366 individuals with BD (2697 female participants [61.8%]; 2627 with BD-I [60.2%]) and 6091 control participants (3767 female participants [61.8%]). Chronotype and daytime-sleepiness PRS were not associated with BD subtypes. Conclusions and Relevance: Per this analysis, BD subtypes differ in genetic liability to insomnia and hypersomnia, providing further evidence that the distinction between BD-I and BD-II has genetic validity. This distinction will be crucial in selecting participants for future research on the role of sleep disturbance in BD.

Mania triggered by sleep loss and risk of postpartum psychosis in women with bipolar disorder.

BACKGROUND: Women with bipolar disorder are at high risk of affective psychoses following childbirth (i.e. "postpartum psychosis", PP) and there is a need to identify which factors underlie this increased risk. Vulnerability to mood dysregulation following sleep loss may influence risk of PP, as childbirth is typified by sleep disruption. We investigated whether a history of mood episodes triggered by sleep loss was associated with PP in women with bipolar disorder (BD). METHODS: Participants were 870 parous women with BD recruited to the Bipolar Disorder Research Network. Lifetime diagnoses of BD and perinatal episodes were identified via interview and case notes. Information on whether mood episodes had been triggered by sleep loss was derived at interview. Rates of PP were compared between women who did and did not report mood episodes following sleep loss. RESULTS: Women who reported sleep loss triggering episodes of mania were twice as likely to have experienced an episode of PP (OR = 2.09, 95% CI = 1.47-2.97, p < 0.001) compared to women who did not report this. There was no significant association between depression triggered by sleep loss and PP (p = 0.526). LIMITATIONS: Data were cross-sectional therefore may be subject to recall bias. We also did not have objective data on sleep disruption that had occurred during the postpartum period or prior to mood episodes. CONCLUSIONS: In clinical practice, a history of mania following sleep loss could be a marker of increased vulnerability to PP, and should be discussed with BD women who are pregnant or planning to conceive.

Do parents know best? Parent-reported vs. child-reported depression symptoms as predictors of future child mood disorder in a high-risk sample.

BACKGROUND: Parents with depression are thought to be unreliable reporters of children's depression symptoms, but findings are contradictory and primarily focus on discrepancies between parent and child reports rather than on the predictive validity of informants. Using a sample of parents with recurrent depression, our analyses utilised data from a prospective high-risk longitudinal study (the Early Prediction of Adolescent Depression study) to investigate whether baseline parental reports of child depression symptoms predicted new onset mood disorder (NOMD) in children. METHODS: The sample included 287 parents with a history of recurrent depression and their adolescent offspring (aged 9-17 at baseline). Families were assessed at three time points. The Child and Adolescent Psychiatric assessment (parent and child versions) was used to assess the number of child depression symptoms (computed separately by informant at baseline) and NOMD at follow-up. All DSM-IV diagnoses were confirmed by two child psychiatrists. RESULTS: Parent reports of child depression symptoms at baseline significantly predicted NOMD in children. Secondary analyses stratifying the sample according to child age showed that, for younger children, parent reports were significantly better at predicting NOMD compared to child reports. For children aged 12 or older, there were no significant differences between parent and child reports in predicting NOMD. The pattern of association remained the same once we controlled for baseline levels of parental depression. LIMITATIONS: Not all parents were currently experiencing an episode of depression at the baseline assessments; the sample consisted predominantly of mothers, thus findings may not be applicable to fathers or families without a history of parental depression. CONCLUSIONS: In this high risk sample, child and parent ratings of depression predict new onset child mood disorder to a similar degree. Clinicians and researchers should give due consideration to parent ratings of their children's depression symptoms, regardless of whether the parent suffers with depression.