Antecedents of incident bipolar disorder in youth
AffiliationCentre for Youth Mental Health
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2021-12-06. This item is currently available to University of Melbourne staff and students only, login required.
© 2017 Dr Aswin Ratheesh
Background: 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.
Keywordsprediction; prevention; bipolar disorder; depression; psychosis; risk factors
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