The Relationship between Sleep-Wake Cycle and Cognitive Functioning in Young People with Affective Disorders

April The Relationship between Sleep-Wake Cycle and Cognitive Functioning in Young People with Affective Disorders Joanne S. Carpenter 0 Rbecca Robillard 0 Rico S. C. Lee 0 Daniel F. Hermens 0 Sharon L. Naismith 0 Django White 0 Bradley Whitwell 0 Elizabeth M. Scott 0 Ian B. Hickie 0 0 Clinical Research Unit, Brain & Mind Research Institute, University of Sydney , Camperdown, NSW , Australia Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16-30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18-30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a 'long sleep' cluster, a 'disrupted sleep' cluster, and a 'delayed and disrupted sleep' cluster. Circadian clusters included a 'strong circadian' cluster, a 'weak circadian' cluster, and a 'delayed circadian' cluster. Medication use differed between clusters. The 'long sleep' cluster displayed significantly worse visual memory performance compared to the 'disrupted sleep' cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement of functioning in young adults early in the course of affective illness. - Funding: IBH was funded by a National Health and Medical Research Council Program Grant (No. 566529) and Australian Fellowship (No. 464914). DFH was supported by a grant from NSW Health Mental Health and Drug & Alcohol Office. SLN was funded by a National Health and Medical Research Council Clinical Development Award (No. 1008117). RR received a postdoctoral training award from the Fonds de la recherche en sante du Quebec. RSCL and JSC were supported by the NHMRC Centre of Research Excellence in Optimising Early Interventions for Young People with Emerging Mood Disorders (No. 1061043). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have read the journals policy and have the following conflicts. DFH has received honoraria for educational seminars from Janssen-Cilag and Eli Lilly. EMS is the (unpaid) Clinical Director of Headspace Services at the BMRI, the (unpaid) Coordinator of the Youth Mental Health Research Program at the BMRI, and Deputy Director of St Vincents Private Hospital Young Adult Mental Health Unit. She has received honoraria for educational seminars related to the clinical management of depressive disorders supported by Servier and Eli Lilly pharmaceuticals. She has participated in a national advisory board for the antidepressant compound Pristiq, manufactured by Pfizer. IBH is a Commissioner in Australias new National Mental Health Commission from 2012. He was a director of headspace: the national youth mental health foundation until January 2012. He was previously the chief executive officer (till 2003) and clinical adviser (till 2006) of beyondblue, an Australian National Depression Initiative. He is the executive director of the Brain and Mind Research Institute, which operates two early-intervention youth services under contract to headspace. He has led a range of community-based and pharmaceutical industrysupported depression awareness and education and training programs. He has led projects for health professionals and the community supported by governmental, community agency and pharmaceutical industry partners (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca) for the identification and management of depression and anxiety. He has received honoraria for presentations of his own work at educational seminars supported by a number of non-government organisations and the pharmaceutical industry (including Servier, Pfizer, AstraZeneca, and Eli Lilly). He is a member of the Medical Advisory Panel for Medibank Private and also a Board Member of Psychosis Australia Trust. He leads an investigator-initiated study of the effects of agomelatine on circadian parameters (supported in part by Servier) and has participated in a multicentre clinical trial of the effects of agomelatine on sleep architecture in depression and a Servier-supported study of major depression and sleep disturbance in primary care settings. The competing interests do not alter the authors adherence to all the PLOS ONE policies on sharing data and materials. Adolescence and young adulthood is a key developmental period with a heightened incidence of affective disorders (defined in this paper to include major depressive disorder, bipolar disorder, and anxiety disorders) [1, 2]. Affective disorders have been associated with a range of cognitive deficits, including dysfunction in areas of new learning, memory, attention, and executive functioning [38]. Many of these deficits are present in the first episode of mental illness [9, 10] and have been shown to persist into remission [1113]. This may be reflective of such deficits being risk-factors for the development or recurrence of these disorders, or epiphenomena of other causal factors or risk-factors. Poorer neuropsychological performance has been linked to poorer clinical, social, and occupational outcomes [1416] and as such uncovering any potential causal or mediational factors is important to identify targets for therapeutic interventions. One factor that could potentially be associated with cognitive dysfunctions in affective disorders is sleep and circadian rhythm disturbance. Sleep disturbances are found in major depressive disorder (difficulty initiating and maintaining sleep, and abnormal sleep duration [17, 18]), anxiety disorders (altered sleep duration, insomnia [1821]), and bipolar disorder (decreased sleep duration during manic and hypomanic episodes [22, 23]). Sleep disturbances in affective disorders oft (...truncated)