Modelling change in neurocognition, symptoms and functioning in young people with emerging mental disorders.

Mental disorders and their functional impacts evolve dynamically over time. Neurocognition and clinical symptoms are commonly modelled as predictors of functioning, however, studies tend to rely on static variables and adult samples with chronic disorders, with limited research investigating change in these variables in young people with emerging mental disorders. These relationships were explored in a longitudinal clinical cohort of young people accessing early intervention mental health services in Australia, around three-quarters of whom presented with a mood disorder (N = 176, aged 12-30 at baseline). Bivariate latent change score models quantified associations between neurocognition (a latent variable of working memory, verbal memory, visuospatial memory, and cognitive flexibility), global clinical symptoms, and functioning (self- and clinician-rated) and their relative change over follow-up (median = 20 months). We found that longitudinal changes in functioning were coupled with changes in global clinical symptoms (ß = -0.43, P < 0.001), such that improvement in functioning was related to improvement in clinical symptoms. Changes in neurocognition were not significantly associated with changes in functioning or clinical symptoms. Main findings were upheld in three sensitivity analyses restricting the sample to: (a) adults aged 18-30; (b) participants with 12-24 months of follow-up; and (c) participants without a psychotic disorder. Our findings show that global symptom reduction and functional improvement are related in young people with emerging mental disorders. More work is needed to determine the temporal precedence of change in these variables. Future studies should apply this methodology to intervention studies to untangle the causal dynamics between neurocognition, symptoms, and functioning.

Cohort profile: the Brain and Mind Centre Optymise cohort: tracking multidimensional outcomes in young people presenting for mental healthcare.

PURPOSE: The Brain and Mind Centre (BMC) Optymise cohort assesses multiple clinical and functional domains longitudinally in young people presenting for mental health care and treatment. Longitudinal tracking of this cohort will allow investigation of the relationships between multiple outcome domains across the course of care. Subsets of Optymise have completed detailed neuropsychological and neurobiological assessments, permitting investigation of associations between these measures and longitudinal course. PARTICIPANTS: Young people (aged 12-30) presenting to clinics coordinated by the BMC were recruited to a research register (n=6743) progressively between June 2008 and July 2018. To date, 2767 individuals have been included in Optymise based on the availability of at least one detailed clinical assessment. MEASURES: Trained researchers use a clinical research proforma to extract key data from clinical files to detail social and occupational functioning, clinical presentation, self-harm and suicidal thoughts and behaviours, alcohol and other substance use, physical health comorbidities, personal and family history of mental illness, and treatment utilisation at the following time points: baseline, 3, 6, 12, 24, 36, 48, and 60 months, and time last seen. FINDINGS TO DATE: There is moderate to substantial agreement between raters for data collected via the proforma. While wide variations in individual illness course are clear, social and occupational outcomes suggest that the majority of cohort members show no improvement in functioning over time. Differential rates of longitudinal transition are reported between early and late stages of illness, with a number of baseline factors associated with these transitions. Furthermore, there are longitudinal associations between prior suicide attempts and inferior clinical and functional outcomes. FUTURE PLANS: Future reports will detail the longitudinal course of each outcome domain and examine multidirectional relationships between these domains both cross-sectionally and longitudinally, and explore in subsets the associations between detailed neurobiological measures and clinical, social and functional outcomes.

Transdiagnostic neurocognitive subgroups and functional course in young people with emerging mental disorders: a cohort study.

BACKGROUND: Neurocognitive impairments robustly predict functional outcome. However, heterogeneity in neurocognition is common within diagnostic groups, and data-driven analyses reveal homogeneous neurocognitive subgroups cutting across diagnostic boundaries. AIMS: To determine whether data-driven neurocognitive subgroups of young people with emerging mental disorders are associated with 3-year functional course. METHOD: Model-based cluster analysis was applied to neurocognitive test scores across nine domains from 629 young people accessing mental health clinics. Cluster groups were compared on demographic, clinical and substance-use measures. Mixed-effects models explored associations between cluster-group membership and socio-occupational functioning (using the Social and Occupational Functioning Assessment Scale) over 3 years, adjusted for gender, premorbid IQ, level of education, depressive, positive, negative and manic symptoms, and diagnosis of a primary psychotic disorder. RESULTS: Cluster analysis of neurocognitive test scores derived three subgroups described as 'normal range' (n = 243, 38.6%), 'intermediate impairment' (n = 252, 40.1%), and 'global impairment' (n = 134, 21.3%). The major mental disorder categories (depressive, anxiety, bipolar, psychotic and other) were represented in each neurocognitive subgroup. The global impairment subgroup had lower functioning for 3 years of follow-up; however, neither the global impairment (B = 0.26, 95% CI -0.67 to 1.20; P = 0.581) or intermediate impairment (B = 0.46, 95% CI -0.26 to 1.19; P = 0.211) subgroups differed from the normal range subgroup in their rate of change in functioning over time. CONCLUSIONS: Neurocognitive impairment may follow a continuum of severity across the major syndrome-based mental disorders, with data-driven neurocognitive subgroups predictive of functional course. Of note, the global impairment subgroup had longstanding functional impairment despite continuing engagement with clinical services.

Modelling associations between neurocognition and functional course in young people with emerging mental disorders: a longitudinal cohort study.

Neurocognitive impairment is commonly associated with functional disability in established depressive, bipolar and psychotic disorders. However, little is known about the longer-term functional implications of these impairments in early phase transdiagnostic cohorts. We aimed to examine associations between neurocognition and functioning at baseline and over time. We used mixed effects models to investigate associations between neurocognitive test scores and longitudinal social and occupational functioning ("Social and Occupational Functioning Assessment Scale") at 1-7 timepoints over five-years in 767 individuals accessing youth mental health services. Analyses were adjusted for age, sex, premorbid IQ, and symptom severity. Lower baseline functioning was associated with male sex (coefficient -3.78, 95% CI -5.22 to -2.34 p < 0.001), poorer verbal memory (coefficient 0.90, 95% CI 0.42 to 1.38, p < 0.001), more severe depressive (coefficient -0.28, 95% CI -0.41 to -0.15, p < 0.001), negative (coefficient -0.49, 95% CI -0.74 to -0.25, p < 0.001), and positive symptoms (coefficient -0.25, 95% CI -0.41 to -0.09, p = 0.002) and lower premorbid IQ (coefficient 0.13, 95% CI 0.07 to 0.19, p < 0.001). The rate of change in functioning over time varied among patients depending on their sex (male; coefficient 0.73, 95% CI 0.49 to 0.98, p < 0.001) and baseline level of cognitive flexibility (coefficient 0.14, 95% CI 0.06 to 0.22, p < 0.001), such that patients with the lowest scores had the least improvement in functioning. Impaired cognitive flexibility is common and may represent a meaningful and transdiagnostic target for cognitive remediation in youth mental health settings. Future studies should pilot cognitive remediation targeting cognitive flexibility while monitoring changes in functioning.

Clinical Stage Transitions in Persons Aged 12 to 25 Years Presenting to Early Intervention Mental Health Services With Anxiety, Mood, and Psychotic Disorders.

Importance: The large contribution of psychiatric disorders to premature death and persistent disability among young people means that earlier identification and enhanced long-term care for those who are most at risk of developing life-threatening or chronic disorders is critical. Clinical staging as an adjunct to diagnosis to address emerging psychiatric disorders has been proposed for young people presenting for care; however, the longer-term utility of this system has not been established. Objectives: To determine the rates of transition from earlier to later stages of anxiety, mood, psychotic, or comorbid disorders and to identify the demographic and clinical characteristics that are associated with the time course of these transitions. Design, Setting, and Participants: A longitudinal, observational study of 2254 persons aged 12 to 25 years who obtained mental health care at 2 early intervention mental health services in Sydney, Australia, and were recruited to a research register between June 18, 2008, and July 24, 2018 (the Brain and Mind Centre Optymise Cohort). Main Outcomes and Measures: The primary outcome of this study was transition from earlier to later clinical stages. A multistate Markov model was used to examine demographic (ie, age, sex, engagement in education, employment, or both) and clinical (ie, social and occupational function, clinical presentation, personal history of mental illness, physical health comorbidities, treatment use, self-harm, suicidal thoughts and behaviors) factors associated with these transitions. Results: Of the 2254 individuals included in the study, mean (SD) age at baseline was 18.18 (3.33) years and 1330 (59.0%) were female. Data on race/ethnicity were not available. Median (interquartile range) follow-up was 14 (5-33) months. Of 685 participants at stage 1a (nonspecific symptoms), 253 (36.9%) transitioned to stage 1b (attenuated syndromes). Transition was associated with lower social functioning (hazard ratio [HR], 0.77; 95% CI, 0.66-0.90), engagement with education, employment, or both (HR, 0.47; 95% CI, 0.25-0.91), manic-like experiences (HR, 2.12; 95% CI, 1.19-3.78), psychotic-like experiences (HR, 2.13; 95% CI, 1.38-3.28), self-harm (HR, 1.42; 95% CI, 1.01-1.99), and older age (HR, 1.27; 95% CI, 1.11-1.45). Of 1370 stage 1b participants, 176 (12.8%) transitioned to stage 2 (full-threshold) disorders. Transition was associated with psychotic-like experiences (HR, 2.31; 95% CI, 1.65-3.23), circadian disturbance (HR, 1.66; 95% CI, 1.17-2.35), psychiatric medication (HR, 1.43; 95% CI, 1.03-1.99), childhood psychiatric disorder (HR, 1.62; 95% CI, 1.03-2.54), and older age (HR, 1.24; 95% CI, 1.05-1.45). Conclusions and Relevance: Differential rates of progression from earlier to later stages of anxiety, mood, psychotic, or comorbid disorders were observed in young persons who presented for care at various stages. Understanding the rate and factors associated with transition assists planning of stage-specific clinical interventions and secondary prevention trials.

What is the prevalence, and what are the clinical correlates, of insulin resistance in young people presenting for mental health care? A cross-sectional study.

OBJECTIVES: To report the distribution and predictors of insulin resistance (IR) in young people presenting to primary care-based mental health services. DESIGN: Cross-sectional. SETTING: Headspace-linked clinics operated by the Brain and Mind Centre of the University of Sydney. PARTICIPANTS: 768 young people (66% female, mean age 19.7±3.5, range 12-30 years). MAIN OUTCOME MEASURES: IR was estimated using the updated homeostatic model assessment (HOMA2-IR). Height and weight were collected from direct measurement or self-report for body mass index (BMI). RESULTS: For BMI, 20.6% of the cohort were overweight and 10.2% were obese. However, <1% had an abnormally high fasting blood glucose (>6.9 mmol/L). By contrast, 9.9% had a HOMA2-IR score >2.0 (suggesting development of IR) and 11.7% (n=90) had a score between 1.5 and 2. Further, there was a positive correlation between BMI and HOMA2-IR (r=0.44, p<0.001). Participants in the upper third of HOMA2-IR scores are characterised by younger age, higher BMIs and depression as a primary diagnosis. HOMA2-IR was predicted by younger age (ß=0.19, p<0.001) and higher BMI (ß=0.49, p<0.001), together explaining 22% of the variance (F(2,361)=52.1, p<0.001). CONCLUSIONS: Emerging IR is evident in a significant subgroup of young people presenting to primary care-based mental health services. While the major modifiable risk factor is BMI, a large proportion of the variance is not accounted for by other demographic, clinical or treatment factors. Given the early emergence of IR, secondary prevention interventions may need to commence prior to the development of full-threshold or major mood or psychotic disorders.

Developing neurocognitive standard clinical care: A study of young adult inpatients.

Neuropsychological assessments have provided the field of psychiatry with important information about patients. As an assessment tool, a neuropsychological battery can be useful in a clinical setting; however, implementation as standard clinical care in an inpatient unit has not been extensively evaluated. A computerized cognitive battery was administered to 103 current young adult inpatients (19.2 ±â€¯3.1 years; 72% female) with affective disorder. Neurocognitive tasks included Verbal Recognition Memory (VRM), Attention Switching (AST), Paired Association Learning (PAL), and Rapid Visual Processing (RVP). Patients also completed a computerized self-report questionnaire evaluating subjective impressions of their cognition. Hierarchical cluster analysis determined three neurocognitive subgroups: cluster 1 (n = 17) showed a more impaired neurocognitive profile on three of the four variables compared to their peers in cluster 2 (n = 59), and cluster 3 (n = 27), who had the most impaired attentional shifting. Two of the four neurocognitive variables were significantly different between all three cluster groups (verbal learning and sustained attention). Overall group results showed an association between poorer sustained attention and increased suicidal ideation. These findings strengthen the idea that neurocognitive profiles may play an important role in better understanding the severity of illness in young inpatients with major psychiatric disorders.

Exploring associations between early substance use and longitudinal socio-occupational functioning in young people engaged in a mental health service.

Neuropsychiatric disorders (including substance misuse) are associated with the greatest burden of functional disability in young people, and contributory factors remain poorly understood. Early-onset substance use is one candidate risk factor which may inform functional prognosis and facilitate direction of interventions aiming to curtail impairment. Accordingly, we modelled associations between early-onset use of alcohol, tobacco, cannabis and amphetamine-type stimulants (ATSs) and longitudinal socio-occupational functioning (indexed by the Social and Occupational Functioning Assessment Scale) in an observational cohort presenting to early intervention mental health services. A clinical proforma collated demographic, clinical, and socio-occupational information for up to 60-months from presentation to services in young people aged 17-30. Of the wider cohort (n = 2398), 446 participants were selected with complete alcohol and substance use data. Latent class analysis was used to derive an 'early-onset' (n = 243) and 'later-onset' class (n = 203) based on age of first use of alcohol, tobacco, cannabis and ATSs. Maximum-likelihood multilevel analyses modelled functioning over time in care and tested associations with substance use latent class, age, gender and diagnosis. Membership in the 'early-onset' class (B = -1.64, p = 0.05), male gender (B = -3.27, p<0.001) and psychotic disorder diagnosis (B = -7.62, p<0.001) were associated with poorer functioning at presentation and at least one other time-point. To our knowledge, this is the first study to explore associations of early-onset substance use and longitudinal functioning in a cohort of young people with mental disorders. The identified factors may be useful for directing specific social (e.g. Social Recovery Therapy) or occupational (e.g. Individual Placement and Support) interventions to at-risk individuals, early in illness course.

A data-driven transdiagnostic analysis of white matter integrity in young adults with major psychiatric disorders.

Diffusion tensor imaging (DTI) has been utilized to index white matter (WM) integrity in the major psychiatric disorders. However, the findings within and across such disorders have been mixed. Given this, transdiagnostic sampling with data-driven statistical approaches may lead to new and better insights about the clinical and functional factors associated with WM abnormalities. Thus, we undertook a cross-sectional DTI study of 401 young adult (18-30 years old) outpatients with a major psychiatric (depressive, bipolar, psychotic, or anxiety) disorder and 61 healthy controls. Participants also completed self-report questionnaires and underwent neuropsychological assessment. Fractional anisotropy (FA) as well as axial (AD) and radial (RD) diffusivity was determined via a whole brain voxel-wise approach (tract-based spatial statistics). Hierarchical cluster analysis was performed on FA scores in patients only, obtained from 20 major WM tracts (that is, association, projection and commissural fibers). The three cluster groups derived were distinguished by having consistently increased or decreased FA scores across all tracts. Compared to controls, the largest cluster (N = 177) showed significantly increased FA in 55% of tracts, the second cluster (N = 169) demonstrated decreased FA (in 90% of tracts) and the final cluster (N = 55) exhibited the most increased FA (in 95% of tracts). Importantly, the distribution of primary diagnosis did not significantly differ among the three clusters. Furthermore, the clusters showed comparable functional, clinical and neuropsychological measures, with the exception of alcohol use, medication status and verbal fluency. Overall, this study provides evidence that among young adults with a major psychiatric disorder there are subgroups with either abnormally high or low FA and that either pattern is associated with suboptimal functioning. Importantly, these neuroimaging-based subgroups appear despite diagnostic and clinical factors, suggesting differential treatment strategies are warranted.

Autism, Early Psychosis, and Social Anxiety Disorder: a transdiagnostic examination of executive function cognitive circuitry and contribution to disability.

The disability burden in clinical cohorts with social impairment is significant, leading to poor functional outcomes. Some of this impairment has been linked to executive dysfunction. In this study, a transdiagnostic approach was taken to identify executive function (EF) processes in young adults that may underpin social impairment and to evaluate their contribution to disability. Comparisons were made between three prominent disorders that are characterized by social impairments, Autism Spectrum Disorder (ASD), Early Psychosis (EP) and Social Anxiety Disorder (SAD), as well as a neurotypically developing group (TYP). We examined whether overall disability could be predicted by neuropsychological and self-report assessments of EF. Our study showed that ASD participants demonstrated impaired performance on most domains of EF compared to the TYP group (mental flexibility, sustained attention and fluency) while the EP group showed impairment on sustained attention and attentional shifting. The SAD participants showed EF impairment on self-report ratings, even though their objective performance was intact. Self-reports of EF explained a significant percentage (17%) of disability in addition to the variance explained by other predictors, and this was particularly important for ASD. This is the first study to compare EF measures across clinical groups of social impairment and suggests unique cognitive-circuitry that underpins disability within groups. Impairments in EF were broad in ASD and predicted disability, EP impairments were specific to attentional processes and SAD impairments likely relate to negative self-monitoring. Self-report, as opposed to performance-based EF, provided best capacity to predict disability. These findings contribute to transdiagnostic circuitry models and intervention strategies.

Distress and sleep quality in young amphetamine-type stimulant users with an affective or psychotic illness.

Misuse of amphetamine-type stimulant (ATS) drugs may disrupt key neurodevelopmental processes in young people and confer protracted neurocognitive and psychopathological harm. ATS users with a co-occurring psychiatric illness are typically excluded from research, reducing generalisability of findings. Accordingly, we conducted a cross-sectional examination of key clinical, sleep, socio-occupational and neurocognitive measures in current, past and never users of ATS drugs who were accessing a youth mental health service (headspace) for affective- or psychotic-spectrum illnesses. Contrary to hypotheses, groups did not differ in psychotic symptomology, socio-occupational functioning or neurocognitive performance. Current ATS users were however significantly more distressed and reported poorer subjective sleep quality and greater subjective sleep disturbances than never users, with a trend toward greater depressive symptomology in current users. Regression analyses revealed that depressive symptoms, daily ATS use and socio-occupational functioning predicted distress, and depressive symptoms and distress predicted subjective sleep quality. Our findings suggest that distress and poor sleep quality reflect a particular pathophysiology among ATS-using patients, which may negatively impact treatment engagement. Delineating the factors that disrupt social and neurobiological development in young people (such as substance use) warrants further investigation, including longitudinal study.

Parallel Changes in Mood and Melatonin Rhythm Following an Adjunctive Multimodal Chronobiological Intervention With Agomelatine in People With Depression: A Proof of Concept Open Label Study.

Background: Agomelatine is a melatonin agonist and 5HT antagonist developed for the treatment of major depressive disorder which also has some effects on the circadian system. Since circadian dysfunctions are thought to play a role in the pathophysiology of depression, some of the mechanism of action of this drug may relate to improvements in circadian rhythms. Objective: This proof of concept open-label study sought to determine if improvements in depressive symptoms following an adjunctive multimodal intervention including agomelatine intake are associated with the magnitude of circadian realignment. This was investigated in young people with depression, a subgroup known to have high rates of delayed circadian rhythms. Methods: Young people with depression received a psychoeducation session about sleep and circadian rhythms, were asked to progressively phase advance their wake up time, and completed an 8 weeks course of agomelatine (25-50 mg). Participants underwent semi-structured psychological assessments, ambulatory sleep-wake monitoring and measurement of melatonin circadian phase before and after the intervention. Results: Twenty-four young adults with depression (17-28 years old; 58% females) completed the study. After the intervention, depressive symptoms were significantly reduced [t (23) = 6.9, p < 0.001] and, on average, the timing of dim light melatonin onset (DLMO) shifted 3.6 h earlier [t (18) = 4.4, p < 0.001]. On average, sleep onset was phase shifted 28 min earlier [t (19) = 2.1, p = 0.047] and total sleep time increased by 24 min [t (19) = -2.6, p = 0.018]. There was no significant change in wake-up times. A strong correlation (r = 0.69, p = 0.001) was found between the relative improvements in depression severity and the degree of phase shift in DLMO. Conclusion: Although this needs to be replicated in larger randomized controlled trials, these findings suggest that the degree of antidepressant response to a multimodal intervention including psychoeducation and agomelatine intake may be associated with the degree of change in evening melatonin release in young people with depression. This offers promising avenues for targeted treatment based on the prior identification of objective individual characteristics.

Lower In vivo Myo-Inositol in the Anterior Cingulate Cortex Correlates with Delayed Melatonin Rhythms in Young Persons with Depression.

Myo-inositol, a second messenger glucose isomer and glial marker, is potentiated by melatonin. In addition to common abnormalities in melatonin regulation, depressive disorders have been associated with reduced myo-inositol in frontal structures. This study examined associations between myo-inositol in the anterior cingulate cortex and the timing of evening melatonin release. Forty young persons with unipolar depression were recruited from specialized mental health services (20.3 ± 3.8 years old). Healthy controls were recruited from the community (21.7 ± 2.6 years old). The timing of dim light melatonin onset (DLMO) was estimated using salivary melatonin sampling. Myo-inositol concentrations (MI/CrPCr ratio) in the anterior cingulate cortex were obtained using proton magnetic resonance spectroscopy. After controlling for age, sex, and CrPCr concentration the depression group had significantly lower MI/CrPCr ratios than healthy controls [F(4, 75) = 11.4, p = 0.001]. In the depression group, later DLMO correlated with lower MI/CrPCr ratio (r = -0.48, p = 0.014). These findings suggest that neurochemical changes in the frontal cortex are associated with circadian disruptions in young persons with depression.

Quantifying the effect of body mass index, age, and depression severity on 24-h activity patterns in persons with a lifetime history of affective disorders.

BACKGROUND: Patients with affective disorders of different ages have been found to present weight changes and different circadian activity patterns. This study assessed the effects of age, Body Mass Index (BMI) and depression severity on the activity-rest cycle in persons with affective disorders using a novel multifactorial 24-h analysis method. METHODS: Two hundred and thirty-six participants aged between 14 and 85 years underwent 5 to 22 days of actigraphy monitoring (mean duration = 14 days). BMI was also recorded and symptom severity was assessed with the Hamilton Depression Rating Scale (HDRS). Participants were divided into two groups: healthy controls (n = 68) and participants with a lifetime diagnosis of affective disorders (n = 168). First, the multiple regression method was employed to formulate the circadian activity pattern in term of the factors age, BMI and HDRS. For each group, the functional linear analysis method was applied to assess the relative effects of the factors. Finally, Wald-tests were used to assess the contribution of each factor on the circadian activity pattern. RESULTS: In the affective disorders group, higher BMI was associated with higher activity levels from 3 am until 5.30 am and with lower activity levels from 10 am until 10.30 pm. Older age was associated with less activity across the day, evening, and night - from 11 am until 5.30 am. Higher HDRS scores were associated with higher activity around 1:30 am. In healthy controls, the effects of BMI and age on activity patterns were less pronounced and affected a narrower portion of the 24-h period. CONCLUSION: These findings suggest that older age and higher BMI are linked to lower daytime activity levels. Higher BMI and worse symptom severity were also associated with nocturnal activity patterns suggestive of sleep disturbances. The influence of age and BMI on 24-h activity profiles appear to be especially pronounced in people with affective disorders.

The relative contributions of psychiatric symptoms and psychotropic medications on the sleep-wake profile of young persons with anxiety, depression and bipolar disorders.

This study investigated the relative contribution of psychiatric symptoms and psychotropic medications on the sleep-wake cycle. Actigraphy and clinical assessments (Brief Psychiatric Rating Scale) were conducted in 146 youths with anxiety, depression or bipolar disorders. Independently of medications, mania symptoms were predictive of lower circadian amplitude and rhythmicity. Independently of diagnosis and symptoms severity: i) antipsychotics were related to longer sleep period and duration, ii) serotonin-norepinephrine reuptake inhibitors to longer sleep period, and iii) agomelatine to earlier sleep onset. Manic symptoms and different subclasses of medications may have independent influences on the sleep-wake cycle of young people with mental disorders.

Sleep-wake profiles predict longitudinal changes in manic symptoms and memory in young people with mood disorders.

Mood disorders are characterized by disabling symptoms and cognitive difficulties which may vary in intensity throughout the course of the illness. Sleep-wake cycles and circadian rhythms influence emotional regulation and cognitive functions. However, the relationships between the sleep-wake disturbances experienced commonly by people with mood disorders and the longitudinal changes in their clinical and cognitive profile are not well characterized. This study investigated associations between initial sleep-wake patterns and longitudinal changes in mood symptoms and cognitive functions in 50 young people (aged 13-33 years) with depression or bipolar disorder. Data were based on actigraphy monitoring conducted over approximately 2 weeks and clinical and neuropsychological assessment. As part of a longitudinal cohort study, these assessments were repeated after a mean follow-up interval of 18.9 months. No significant differences in longitudinal clinical changes were found between the participants with depression and those with bipolar disorder. Lower sleep efficiency was predictive of longitudinal worsening in manic symptoms (P = 0.007). Shorter total sleep time (P = 0.043) and poorer circadian rhythmicity (P = 0.045) were predictive of worsening in verbal memory. These findings suggest that some sleep-wake and circadian disturbances in young people with mood disorders may be associated with less favourable longitudinal outcomes, notably for subsequent manic symptoms and memory difficulties.

Dysregulated sleep-wake cycles in young people are associated with emerging stages of major mental disorders.

AIM: To determine if disturbed sleep-wake cycle patterns in young people with evolving mental disorder are associated with stages of illness. METHODS: The sleep-wake cycle was monitored using actigraphy across 4 to 22 days. Participants (21 healthy controls and 154 persons seeking help for mental health problems) were aged between 12 and 30 years. Those persons seeking mental health care were categorized as having mild symptoms (stage 1a), an 'attenuated syndrome' (stage 1b) or an 'established mental disorder' (stage 2+). RESULTS: The proportions of individuals with a delayed weekdays sleep schedule increased progressively across illness stages: 9.5% of controls, 11.1% of stage 1a, 25.6% of stage 1b, and 50.0% of stage 2+ (χ(2) (3 d.f.) = 18.4, P < 0.001). A similar pattern was found for weekends (χ(2) (3 d.f.) = 7.6, P = 0.048). Compared with controls, stage 1b participants had later sleep onset on weekends (P = 0.015), and participants at stages 1b and 2+ had later sleep offset on both weekdays and weekends (P < 0.020). Compared with controls, all participants with mental disorders had more wake after sleep onset (P < 0.029) and those at stages 1a and 2+ had lower sleep efficiency (P < 0.040). Older age, medicated status and later weekdays sleep offset were found to be the three strongest correlates of later versus earlier clinical stages. CONCLUSIONS: In relation to clinical staging of common mental disorders in young people, the extent of delayed sleep phase is associated with more severe or persistent phases of illness.

Clinical correlates of chronotypes in young persons with mental disorders.

While important changes in circadian rhythms take place during adolescence and young adulthood, it is unclear how circadian profiles during this period relate to emerging mental disorders. This study aimed to: (i) characterise morningness-eveningness preference in young people with primary anxiety, depression, bipolar or psychotic disorders as compared to healthy controls, and (ii) to investigate associations between morningness-eveningness preference and the severity of psychiatric symptoms. Four hundred and ninety-six males and females aged between 12 and 30 years were divided into five groups according to primary diagnosis. The Hamilton Depression Rating Scale and the Brief Psychiatric Rating Scale were administered by a research psychologist and participants completed the Kessler Psychological Distress Scale and the Horne-Östberg Morningness-Eveningness Questionnaire (ME). ME scores were significantly lower (i.e. higher levels of "eveningness") in all patient diagnosis subgroups compared to the control group. The psychosis group had higher ME scores than the depression and anxiety groups. Compared to the control group, the anxiety, depression and bipolar subgroups had a significantly higher proportion of "moderate evening" types, with a similar trend for the psychosis group. The proportion of "extreme evening" types was significantly higher in the anxiety and depression subgroups than in the control group. Lower ME scores correlated with worse psychological distress in males from the bipolar group. Lower ME scores correlated with higher depression severity in females with depression and in males with bipolar disorder. These results suggest that young persons with various mental disorders, especially those with affective disorders, present with a stronger "eveningness" preference and higher rates of evening chronotypes than healthy controls from the same age group. Later chronotypes were generally associated with worse psychological distress and symptoms severity. These associations were modulated by sex and primary diagnosis.

The relationship between sleep-wake cycle and cognitive functioning in young people with affective disorders.

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.

Body mass, cardiovascular risk and metabolic characteristics of young persons presenting for mental healthcare in Sydney, Australia.

OBJECTIVES: To determine the body mass, cardiovascular and metabolic characteristics of young people presenting for mental healthcare. DESIGN: Cross-sectional assessments of body mass, cardiovascular and metabolic risk factors. SETTING: Two primary-care based sites in Sydney, Australia for young people in the early stages of mental disorders. PARTICIPANTS: A clinical sample of young people (12-30 years) with mental health problems. OUTCOME MEASURES: Daily smoking rates, body mass index (BMI), blood glucose and lipids, blood pressure (BP) and pulse rate. RESULTS: Of 1005 young people who had their BMI determined (62% female; 19.0±3.5 years), three quarters (739/1005) also had BP recordings and one-third (298/1005) had blood sampling. Clinically, 775 were assigned to one of three diagnostic categories (anxious-depression: n=541; mania-fatigue, n=104; developmental-psychotic n=130). The profile of BMI categories approximated that of the comparable segments of the Australian population. Older age, lower levels of social functioning and higher systolic BP were all associated with high BMI. In a subset (n=129), current use of any psychotropic medication was associated (p<0.05) with increased BMI. Almost one-third of cases were current daily smokers (compared to population rate of 11%). Males had a higher proportion of raised glucose and high-density lipoprotein (HDL) compared to females (9.3% and 34.1% vs 2.1% and 5.9%, respectively). Overall, there was no relationship between BMI and fasting glucose but significant relationships with triglycerides and HDL were noted. Furthermore, there were no significant relationships between diagnostic subgroup and metabolic profiles. CONCLUSIONS: Daily smoking rates are increased among young people presenting for mental healthcare. However, these young people do not demonstrate adverse cardiometabolic profiles. The high levels of smoking, and association of BMI with adverse social circumstances, suggest that risk factors for chronic disease are already present and likely to be compounded by medication and social disadvantage.