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Background Interventions early in the course of bipolar disorder (BD) may have the potential to limit its functional and symptomatic impact. However, the implementation of specific early interventions for BD has been limited which may at least partly be due to the lack of guidelines focused on the early illness stages. We therefore aimed to review the current recommendations for early stage BD from clinical practice guidelines. Methods We searched PubMED and PsychINFO for clinical guidelines for BD published in the ten years prior to 1 November 2018. Recommendations from identified guidelines that addressed early stage BD or first episode mania were consolidated and compared. We also reviewed the guidelines relating to adolescents with BD to complement the guidelines related to those in the early illness course. Results We identified fourteen international and national guidelines on BD or affective psychoses. Most guidelines contained a separate section on adolescents, but only a few referred specifically to early stage BD. There were no consistent recommendations for early stage disorder, except with respect to the indications for maintenance medication treatments. For adolescents, there was a consistent recommendation for the use of second generation antipsychotics for treating acute mania. Limitation The main limitation is that the identified guidelines did not include primary data that clearly separated illness and developmental stages. Conclusions There is a lack of emphasis on early BD among widely-respected current clinical guidelines, likely reflecting the dearth of primary data. Future evidence or consensus-based recommendations could significantly inform clinical practice for this population.

Background The impact of guideline concordance on naturalistic maintenance treatment outcomes in BD is not known. We sought to evaluate the effect of guideline-concordant care on symptomatic, course and functional outcomes in youth with early-stage BD-I. Methods In this file audit study, we examined the prospective course of 64 clients with first treatment seeking manic episode of BD-I. Eighteen-month outcome measures included Clinical Global Impressions Scale - Bipolar Version (CGI-BP), Social and Occupational Functioning Assessment Scale (SOFAS) and number of relapses. Correlations and hierarchical linear regressions were used to examine the relationships between guideline concordance and outcomes, while controlling for potential confounders. Results Although higher guideline-concordant care in the maintenance phase was associated with a higher discharge CGI-BP score and thus worse outcome, baseline CGI-BP and insight were more predictive of illness severity at follow-up than guideline concordance. There was no association with SOFAS and guideline-concordant care at follow-up. Greater concordance with maintenance medication guideline statements was also associated with greater number of relapses even after controlling for sex, medication adherence, duration of care and baseline illness severity. Limitations This study was limited by sample size and its single pool of clients which may limit generalizability. Conclusions Contrary to our hypotheses, higher guideline concordance was associated with worse outcomes, although this relationship was moderated by the client's illness characteristics, severity and insight. More unwell youth with poor insight, greater severity, and mixed/rapid cycling features may need other interventions or modified guidelines.

Background Premorbid characteristics may help predict the highly variable functional and illness outcomes of young people with early stage Bipolar Disorder (BD). We sought to examine the relationships between premorbid adjustment and short to medium-term outcomes after a first treated episode of mania. Methods We examined the baseline and 18-month follow-up characteristics of 117 participants with first episode of mania, treated at two tertiary early intervention services in Melbourne, Australia. The baseline demographic, family history, diagnoses, comorbidity and clinical features were determined using unstructured questionnaires and structured diagnostic interviews. Premorbid adjustment was determined using the Premorbid Adjustment Scale (PAS), the components of which were identified using a principal component analysis. Eighteen-month follow-up outcome measures included the Clinical Global Impressions scale, Social and Occupational Functioning Assessment Scale and the Heinrichs’ Quality of Life Scale (QLS). Correlations and linear regressions were utilised to examine the relationships between component scores and outcomes, while controlling for baseline and follow-up confounders. Results The social adjustment component of the PAS correlated with the interpersonal relations ( r s = −0.46, p r s =−0.39, p = 0.004). Premorbid adjustment did not predict illness severity or objective functioning. Limitations Lack of information on cognition, personality factors and prodromal symptoms limited the assessment of their impact on outcomes. Conclusions Impairments in domains of premorbid adjustment may be early markers of persistent difficulties in social and vocational functioning and may benefit from targeted interventions.

Background Cognitive deficits have been well documented in individuals with bipolar disorder (BD) after the first episode of mania. However, little is known about the presence of such deficits prior to the initial manic episode. Methods Participants were recruited from a cohort of 416 young people who were at ultra-high risk (UHR) for psychosis and were followed up between 4 and 13 years later. The current report is of 16 participants who developed BD over a mean follow-up period of 8.2 years (UHR-BD). Baseline demographic, clinical and neurocognitive assessment scores were compared with those of 46 age and gender matched UHR subjects who did not transition to psychosis or BD over the follow-up period (UHR-NT) and 66 healthy comparison subjects. Results UHR-BD subjects had lower global functioning at baseline compared with UHR-NT subjects. There were no significant differences between UHR-BD and UHR-NT subjects on baseline demographic and neurocognitive characteristics. UHR-BD subjects had lower test performance than HC on picture completion, Trail-Making Tests and measures of global intelligence. Limitations Small sample size, limited and variable neurocognitive tests utilised and the confounding effects of psychotic symptoms might have impacted on the ability to detect meaningful clinical and neurocognitive differences. Conclusions In this exploratory study, neurocognition in young people who later develop BD is similar to those of subjects who are at a high risk for psychotic disorders, but there may be certain neurocognitive markers that distinguish this group from unaffected and healthy young people.

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 ¼14.1, po0.001) or a family history of SUD (67% vs 12.5%, χ 2 ¼6.0, p¼0.01) were associated with development of BD. The sub-threshold mania subgroup of BAR criteria was also associated with 12month 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.

BACKGROUND: Identification of earlier stages of Bipolar Disorder (BD), even prior to the first manic episode, may help develop interventions to prevent or delay the onset of BD. However, reliable and valid instruments are necessary to ascertain such earlier stages of BD. The aim of the current review was to identify instruments that had predictive validity and utility for BD for use in early intervention (EI) settings for the prevention of BD. METHODS: We undertook a systematic examination of studies that examined participants without BD I or II at baseline and prospectively explored the predictive abilities of instruments for BD onset over a period of 6 months or more. The instruments and the studies were rated with respect to their relative validity and utility predicting onset of BD for prevention or early intervention. Odds ratios and area under the curve (AUC) values were derived when not reported. RESULTS: Six studies were included, identifying five instruments that examined sub-threshold symptoms, family history, temperament and behavioral regulation. Though none of the identified instruments had been examined in high-quality replicated studies for predicting BD, two instruments, namely the Child Behavioral Checklist - Pediatric BD phenotype (CBCL-PBD) and the General Behavioral Inventory - Revised (GBI-R), had greater levels of validity and utility. LIMITATION: Non-inclusion of studies and instruments that incidentally identified BD on follow-up limited the breadth of the review. CONCLUSION: Instruments that test domains such as subthreshold symptoms, behavioral regulation, family history, and temperament hold promise in predicting BD onset.