Empirically driven transdiagnostic stages in the development of mood, anxiety and psychotic symptoms in a cohort of youth followed from birth

Staging models with transdiagnostic validity across mood, psychotic, and anxiety disorders could advance early intervention efforts as well as our understanding of the common underpinnings of such psychopathology. However, there are few well-supported operationalisations for such transdiagnostic models, particularly in community-based samples. We aimed to explore the inter-relationships among mood, psychotic, and anxiety symptom stages, and their common risk factors to develop data-informed transdiagnostic stages. We included participants from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective ongoing birth cohort study. We developed operational thresholds for stages of depressive, hypomanic, anxiety, and psychotic symptoms based on the existing literature, refined further by expert consensus. We selected 1b level as the primary stage or outcome of interest. This represents moderate symptoms that are likely to be associated with the onset of the need for clinical mental health care. We used questionnaire and clinic data completed by young people ages 18 and 21 years. We used descriptive methods and network analyses to examine the overlap among Stage 1b psychopathology. We then examined the patterns of relationships between several risk factors and 1b stages using logistic regressions. Among 3269 young people with data available to determine all symptom stages, 64.3% were female and 96% Caucasian. Descriptive and network analyses indicated that 1b level depressive, anxiety, and psychotic symptom stages were inter-related while hypomania was not. Similarly, anxiety, depressive, and psychotic 1b stages were associated with the female sex, more emotional and behavioral difficulties in early adolescence, and life events in late adolescence. Hypomania was not related to any of these risk factors. Given their inter-relationships and similar risk factors, anxiety, psychotic and depressive, symptoms could be combined to form a transdiagnostic stage in this cohort. Such empirical transdiagnostic stages could help with prognostication and indicated prevention in youth mental health

Prospective progression from high-prevalence disorders to bipolar disorder: exploring characteristics of pre-illness stages

BACKGROUND: Identification of risk factors within precursor syndromes, such as depression, anxiety or substance use disorders (SUD), might help to pinpoint high-risk stages where preventive interventions for Bipolar Disorder (BD) could be evaluated. METHODS: We examined baseline demographic, clinical, quality of life, and temperament measures along with risk clusters among 52 young people seeking help for depression, anxiety or SUDs without psychosis or BD. The risk clusters included Bipolar At-Risk (BAR) and the Bipolarity Index as measures of bipolarity and the Ultra-High Risk assessment for psychosis. The participants were followed up for 12 months to identify conversion to BD. Those who converted and did not convert to BD were compared using Chi-Square and Mann Whitney U tests. RESULTS: The sample was predominantly female (85%) and a majority had prior treatment (64%). Four participants converted to BD over the 1-year follow up period. Having an alcohol use disorder at baseline (75% vs 8%, χ(2)=14.1, p<0.001) or a family history of SUD (67% vs 12.5%, χ(2)=6.0, p=0.01) were associated with development of BD. The sub-threshold mania subgroup of BAR criteria was also associated with 12-month BD outcomes. The severity of depressive symptoms and cannabis use had high effects sizes of association with BD outcomes, without statistical significance. CONCLUSIONS AND LIMITATIONS: The small number of conversions limited the power of the study to identify associations with risk factors that have previously been reported to predict BD. However, subthreshold affective symptoms and SUDs might predict the onset of BD among help-seeking young people with high-prevalence disorders

Bipolar at-risk criteria: an examination of which clinical features have optimal utility for identifying youth at risk of early transition from depression to bipolar disorders

Background: A clinical and research challenge is to identify which depressed youth are at risk of “early transition to bipolar disorders (ET-BD).” This 2-part study (1) examines the clinical utility of previously reported BD at-risk (BAR) criteria in differentiating ET-BD cases from unipolar depression (UP) controls; and (2) estimates the Number Needed to Screen (NNS) for research and general psychiatry settings. Methods: Fifty cases with reliably ascertained, ET-BD I  and II cases were matched for gender and birth year with 50 UP controls who did not develop BD over 2 years. We estimated the clinical utility for finding true cases and screening out non-cases for selected risk factors and their NNS. Using a convenience sample (N = 80), we estimated the NNS when adjustments were made to account for data missing from clinical case notes. Results: Sub-threshold mania, cyclothymia, family history of BD, atypical depression symptoms and probable antidepressant-emergent elation, occurred significantly more frequently in ET-BD youth. Each of these “BARDepression” criteria demonstrated clinical utility for screening out non-cases. Only cyclothymia demonstrated good utility for case finding in research settings; sub-threshold mania showed moderate utility. In the convenience sample, the NNS for each criterion ranged from ~4 to 7.  Conclusions: Cyclothymia showed the optimum profile for case finding, screening and NNS in research settings. However, its presence or absence was only reported in 50% of case notes. Future studies of ET-BD instruments should distinguish which criteria have clinical utility for case finding vs screening

Implementation of the Enhanced Moderated Online Social Therapy (MOST+) Model Within a National Youth E-Mental Health Service (eheadspace): Protocol for a Single Group Pilot Study for Help-Seeking Young People

Background: There is a substantial need for youth electronic mental health (e-mental health) services. In addressing this need, our team has developed a novel moderated online social therapy intervention called enhanced moderated online social therapy (MOST+). MOST+ integrates real-time, clinician-delivered Web chat counseling, interactive user-directed online therapy, expert and peer moderation, and private and secure peer-to-peer social networking. MOST+ has been designed to give young people immediate, 24-hour access to anonymous, evidence-based, and short-term mental health care. Objective: The primary aims of this pilot study were to determine the feasibility, acceptability, and safety of the intervention. Secondary aims were to assess prepost changes in key psychosocial outcomes and collect qualitative data for future intervention refinement. Methods: MOST+ will be embedded within eheadspace, an Australian youth e-mental health service, and will be evaluated via an uncontrolled single-group study. Approximately 250 help-seeking young people (16-25 years) will be progressively recruited to the intervention from the eheadspace home page over the first 4 weeks of an 8-week intervention period. All participants will have access to evidence-based therapeutic content and integrated Web chat counseling. Additional access to moderated peer-to-peer social networking will be granted to individuals for whom it is deemed safe and appropriate, through a three-tiered screening process. Participants will be enrolled in the MOST+ intervention for 1 week, with the option to renew their enrollment across the duration of the pilot. Participants will complete a survey at enrollment to assess psychological well-being and other mental health outcomes. Additional assessment will occur following account deactivation (ie, after participant has opted not to renew their enrollment, or at trial conclusion) and will include an online survey and telephone interview assessing psychological well-being and experience of using MOST+. Results: Recruitment for the study commenced in October 2017. We expect to have initial results in March 2018, with more detailed qualitative and quantitative analyses to follow. Conclusions: This is the first Australia-wide research trial to pilot an online social media platform merging real-time clinical support, expert and peer moderation, interactive online therapy, and peer-to-peer social networking. The importance of the project stems from the need to develop innovative new models for the efficient delivery of responsive evidence-based online support to help-seeking young people. If successful, this research stands to complement and enhance e-mental health services in Australia

Antecedents of incident bipolar disorder in youth

© 2017 Dr Aswin RatheeshBackground: Bipolar disorder (BD) is a serious mental illness characterised by episodes of mania and depression. The disability associated with this disorder and the observation that at least a sub-proportion have a progressive course suggests that early or preventive interventions may be an effective strategy to minimise the disability. However, prevention efforts for BD require characterisation of targets for such interventions. Aims and objectives: Thus, the overall aim of this research program was to describe the pre-onset illness stages related to the development of incident (hypo)manic episodes and their associated functional impairment. Specifically, we aimed to examine clinical populations where preventive efforts may be more feasible. The objectives included identification of i) baseline characteristics associated with later BD among non-bipolar help-seeking youth; ii) rates and predictors of transition from major depressive disorder (MDD) to BD in previously published studies; iii) instruments that have prospective predictive validity in identifying BD and iv) the precursors of functional impairment in the post-illness period. Methods: This thesis comprises five studies that have examined these issues using diverse methodologies – using systematic review, meta-analyses and longitudinal cohort designs. Three studies involved examining baseline characteristics associated with the development of later BD from non-bipolar states. One study identified the instruments that have been used to predict the later onset of BD using a systematic review, while the final study examined the pre-onset predictors of later functioning among young people with first episode BD. Main results: The characteristics associated with later BD in the two cohort studies included subthreshold manic symptoms, comorbid substance use, severity of depression, antidepressant use and lower functioning. Meta-analyses identified that family history of BD, comorbid psychotic symptoms and lower age of onset of depression was predictive of transition from MDD to BD. The systematic review identified few instruments with prospective validity for predicting BD onset that had been replicated in clinical cohorts. However, instruments with validity in non-clinical cohorts, or those without replication were described. Across the first four studies, combinations of risk factors were associated with a greater risk of transition to BD. Poor premorbid adjustment in the pre-onset phase was predictive of later functioning among youth with first episode mania. Discussion: The findings of these studies point to the need to use combinations of risk factors identified using validated instruments, particularly in young people to predict the onset of BD. This may then help develop preventive interventions that may be tested in studies that are feasible and have adequate statistical power. Incorporating functional precursors into pre-illness stages may help with prevention of functional impairments. A putative instrument which may decrease measurement bias is also proposed. The primary limitation of the included studies was in the post-hoc nature of analyses and the associated lack of availability of all possible baseline confounders. Additionally, low statistical power limited the ability to examine certain associations. Future studies should examine multiple confounding variables in longitudinal cohorts of youth and young adults. Larger cohorts that are enriched for multiple risk factors may help improve statistical power