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,6.9 mmol/L). By contrast, 9.9% had a HOMA2-IR score \u3e2.0 (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 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

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

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

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

Thoughts of death or suicidal ideation are common in young people aged 12 to 30 years presenting for mental health care

<p>Abstract</p> <p>Background</p> <p>Reducing suicidal behaviour is a major public health goal. Expanding access to care has been identified as a key strategy. In Australia, a national network of primary-care based services (<it>headspace</it>) has been established for young people with mental ill-health. This study determines the socio-demographic, psychopathological and illness-stage correlates of suicidal ideation in young persons attending <it>headspace</it> services.</p> <p>Methods</p> <p>Suicidal ideation was recorded using the specific suicide item of the Hamilton Depression Rating Scale (HDRS) in a cohort of subjects aged 12-30 years (N = 494) attending <it>headspace</it> services.</p> <p>Results</p> <p>Of the 494 young persons assessed, 32% (158/494) had a positive response to any level of the HDRS suicide item, consisting of 16% (77/494) reporting that life was not worth living and a further 16% (81/494) reported thoughts of death or suicidal ideation. Young women (19%; 94/494) were more likely to report any positive response as compared with young men (13%; 64/494) [χ²(2,494) = 13.6, p < .01]. Those with ‘attenuated syndromes’ reported positive responses at rates comparable to those with more established disorders (35% vs. 34%; χ²(1,347) = 0.0, p = 0.87). However, more serious levels of suicidal ideation were more common in those with depressive disorders or later stages of illness. In multivariate analyses, the major predictors of the degree of suicidal ideation were increasing levels of clinician-rated depressive symptoms (beta = 0.595, p < .001), general psychopathology (beta = 0.198, p < .01), and self-reported distress (beta = 0.172, p < .05).</p> <p>Conclusions</p> <p>Feelings that life is not worth living, thoughts of death or suicidal ideation are common in young people seeking mental health care. These at-risk cognitions are evident before many of these individuals develop severe or persistent mental disorders. Thoughts of death or suicidal ideation may well need to be a primary intervention target in these young people.</p

Distress and disability in young adults presenting to clinical services with mood disorders

Background: Distress and/or dysfunction are well established as key reasons for help-seeking. We explore the characteristics of groups defined by high or low distress or disability in young people with unipolar depression (UP) or bipolar disorder (BD). Methods: Individuals aged 12 to 25 years presenting to youth mental health services for the first time with a primary diagnosis of UP or BD were assessed using the Kessler Psychological Distress Scale (Kessler-10) and the Work and Social Adjustment Scale (WSAS). Four groups with high or low distress or impairment were defined (according to scores above or below the group medians for the Kessler-10 and WSAS). Multinomial logistic regression (MNLR) was used to examine how cases with high levels of distress and disability (reference group) differed from the other three groups. Results and discussion: The sample comprised 1,746 cases (90% UP, 56% female) with a median age of 17.5 years. Median scores on the Kessler-10 and WSAS were both high (30 and 20, respectively) and were significantly inter-correlated (r = 0.62); the high impairment/distress group was the largest sub-group (39% of cases). The MNLR analysis demonstrated that younger age was associated with lower impairment groups (irrespective of distress level), whilst male gender was associated with lower distress (irrespective of impairment). Compared to the low impairment/distress cases, the high impairment/distress group was significantly more likely to use cannabis and/or alcohol. Age, substance use and possibly gender are probably better predictors of distress/impairment sub-group than mood disorder sub-type in youth.8 page(s

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 (β = −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

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

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\u3c0.001) and psychotic disorder diagnosis (B = -7.62, p\u3c0.001) 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