Centre for Youth Mental Health - Research Publications

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    Impact of irritability: a 2-year observational study of outpatients with bipolar I or schizoaffective disorder
    Berk, L ; Hallam, KT ; Venugopal, K ; Lewis, AJ ; Austin, DW ; Kulkarni, J ; Dodd, S ; de Castella, A ; Fitzgerald, PB ; Berk, M (WILEY, 2017-05)
    OBJECTIVES: Many people experience irritability when manic, hypomanic, or depressed, yet its impact on illness severity and quality of life in bipolar and schizoaffective disorders is poorly understood. This study aimed to examine the relationship between irritability and symptom burden, functioning, quality of life, social support, suicidality, and overall illness severity in a naturalistic cohort of people with bipolar I or schizoaffective disorder. METHODS: We used data from 239 adult outpatients with bipolar I or schizoaffective disorder in the Bipolar Comprehensive Outcomes Study (BCOS) - a non-interventional observational study with a 2-year follow-up period. Baseline demographic and clinical characteristics of participants with and without irritability were compared. A mixed-model repeated measures analysis was conducted to examine the longitudinal effect of irritability on clinical and quality-of-life variables over follow-up using significant baseline variables. RESULTS: At baseline, 54% of participants were irritable. Baseline irritability was associated with illness severity, mania, depression, psychotic symptoms, suicidality, poor functioning, and quality of life, but not diagnosis (schizoaffective/bipolar disorder). Participants with irritability were less likely to have a partner and perceived less adequate social support. On average, over follow-up, those with irritability reported more symptoms, functional impairment, and suicidality. Furthermore, the effects of irritability could not be fully explained by illness severity. CONCLUSIONS: Irritability was associated with more negative symptomatic, functional, and quality-of-life outcomes and suicidality. The identification, monitoring, and targeted treatment of irritability may be worth considering, to enhance health and wellbeing outcomes for adults with bipolar and schizoaffective disorders.
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    Treatment and outcomes of an Australian cohort of outpatients with bipolar I or schizoaffective disorder over twenty-four months: implications for clinical practice
    Kulkarni, J ; Filia, S ; Berk, L ; Filia, K ; Dodd, S ; de Castella, A ; Brnabic, AJM ; Lowry, AJ ; Kelin, K ; Montgomery, W ; Fitzgerald, PB ; Berk, M (BMC, 2012-12-17)
    BACKGROUND: The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with 'real-world' treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication. METHODS: Participants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale - Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data. RESULTS: On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts. CONCLUSIONS: Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.
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    Staging in bipolar disorder: from theoretical framework to clinical utility
    Berk, M ; Post, R ; Ratheesh, A ; Gliddon, E ; Singh, A ; Vieta, E ; Carvalho, AF ; Ashton, MM ; Berk, L ; Cotton, SM ; McGorry, PD ; Fernandes, BS ; Yatham, LN ; Dodd, S (WILEY, 2017-10)
    Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage-specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage-specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at-risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative-type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper are to: a) explore the current level of evidence supporting the descriptive staging of the syndromal pattern of bipolar disorder; b) describe preliminary attempts at validation; c) make recommendations for the direction of further studies; and d) provide a distillation of the potential clinical implications of staging in bipolar disorder within a broader transdiagnostic framework.
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    Impact of comorbid anxiety disorders and obsessive-compulsive disorder on 24-month clinical outcomes of bipolar I disorder
    Kim, S-W ; Berk, L ; Kulkarni, J ; Dodd, S ; de Castella, A ; Fitzgerald, PB ; Amminger, GP ; Berk, M (ELSEVIER SCIENCE BV, 2014-09)
    BACKGROUND: This study investigated the impact of comorbid obsessive-compulsive disorder (OCD) and four anxiety disorders [panic disorder (PD), agoraphobia, social anxiety disorder (SAD), and generalized anxiety disorder (GAD)] on the clinical outcomes of bipolar disorder. METHODS: This study analysed data of 174 patients with bipolar I disorder who participated in the prospective observational study. Participants were assessed every 3 months for 24 months. The primary outcome measure was the achievement of symptomatic remission, defined by a total score on the Young Mania Rating Scale (YMRS) of ≤12 and a total score on the 21-item Hamilton Depression Rating Scale (HAMD-21) of ≤8. RESULTS: Comorbidity was associated with decreased likelihood of remission. However, the impact of individual disorders on outcome differed according to clinical and treatment situations. Most comorbid anxiety disorders and OCD had a negative effect on remission during the first year of evaluation, as measured by the HAMD-21, and in patients taking a conventional mood stabilizer alone. However, the association with poorer outcome was observed only for a few specific comorbid disorders in the second year (GAD and OCD), as measured by YMRS-defined remission (OCD), and in patients with olanzapine therapy (GAD and OCD). LIMITATIONS: Follow-up evaluation of comorbid disorders was lacking. CONCLUSIONS: Comorbid anxiety disorders and OCD negatively influenced the clinical course of bipolar disorder. Specifically, OCD had a consistently negative impact on the outcome of bipolar I disorder regardless of clinical situation. Effective strategies for the control of these comorbidities are required to achieve better treatment outcomes.