Is age of onset associated with severity, prognosis, and clinical features in bipolar disorder? A meta-analytic review.

OBJECTIVES: To identify clinical characteristics and adverse outcomes associated with an earlier age of onset of bipolar disorder. METHODS: A comprehensive search yielded 15 empirical papers comparing clinical presentation and outcomes in individuals with bipolar disorder grouped according to age of onset (total N=7370). The following variables were examined to determine odds ratios (ORs) and 95% confidence intervals (CIs): presence of Axis I comorbidity, rapid cycling, psychotic symptoms, mixed episodes (DSM-IV), lifetime suicide attempts, lifetime alcohol and substance abuse, symptom severity, and treatment delay. RESULTS: Early age of onset was found to be associated with longer delay to treatment (Hedges' g=0.39, P=.001), greater severity of depression (Hedges' g=0.42, P<.001), and higher levels of comorbid anxiety (OR=2.34, P<.001) and substance use (OR=1.80, P<.001). Surprisingly, no association was found between early age of onset and clinical characteristics such as psychotic symptoms or mixed episodes as defined by DSM-IV. CONCLUSIONS: Earlier age of onset of bipolar disorder is associated with factors that can negatively impact long-term outcomes such as increased comorbidity. However, no association was found between early onset and indicators of severity or treatment resistance such as psychotic symptoms. Clinical features found to have the strongest relationship with early age of onset were those potentially amenable to pharmacological and psychological treatment. Results highlight the importance of early identification and provide potential areas of focus for the development of early intervention in bipolar disorder.

What clinical features precede the onset of bipolar disorder?

Despite a growing number of reports, there is still limited knowledge of the clinical features that precede the onset of bipolar disorder (BD). To explore this, we investigated baseline data from a prospectively evaluated longitudinal cohort of subjects aged 12-30 years to compare: first, lifetime rates of clinical features between a) subjects at increased genetic risk for developing BD ('AR'), b) participants from families without mental illness ('controls'), and c) those with established BD; and, second, prior clinical features that predict the later onset of affective disorders in these same three groups. This is the first study to report such comparisons between these three groups (though certainly not the first to compare AR and control samples). 118 AR participants with a parent or sibling with BD (including 102 with a BD parent), 110 controls, and 44 BD subjects were assessed using semi-structured interviews. AR subjects had significantly increased lifetime risks for depressive, anxiety and behavioural disorders compared to controls. Unlike prior reports, preceding anxiety and behavioural disorders were not found to increase risk for later onset of affective disorders in the AR sample, perhaps due to limited sample size. However, preceding behavioural disorders did predict later onset of affective disorders in the BD sample. The findings that i) AR subjects had higher rates of depressive, anxiety and behavioural disorders compared to controls, and ii) prior behavioural disorders increased the risk to later development of affective disorders in the BD group, suggest the possibility of therapeutic targeting for these disorders in those at high genetic risk for BD.