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Clinical predictors of conversion to bipolar disorder in a prospective longitudinal familial high-risk sample: focus on depressive features

  • Andrew Frankland (a1) (a2), Gloria Roberts (a1) (a2), Ellen Holmes-Preston (a1) (a2), Tania Perich (a1) (a2) (a3), Florence Levy (a1) (a4), Rhoshel Lenroot (a1) (a5), Dusan Hadzi-Pavlovic (a1) (a2), Michael Breakspear (a1) (a6) and Philip B. Mitchell (a1) (a2)...



Identifying clinical features that predict conversion to bipolar disorder (BD) in those at high familial risk (HR) would assist in identifying a more focused population for early intervention.


In total 287 participants aged 12–30 (163 HR with a first-degree relative with BD and 124 controls (CONs)) were followed annually for a median of 5 years. We used the baseline presence of DSM-IV depressive, anxiety, behavioural and substance use disorders, as well as a constellation of specific depressive symptoms (as identified by the Probabilistic Approach to Bipolar Depression) to predict the subsequent development of hypo/manic episodes.


At baseline, HR participants were significantly more likely to report ⩾4 Probabilistic features (40.4%) when depressed than CONs (6.7%; p < .05). Nineteen HR subjects later developed either threshold (n = 8; 4.9%) or subthreshold (n = 11; 6.7%) hypo/mania. The presence of ⩾4 Probabilistic features was associated with a seven-fold increase in the risk of ‘conversion’ to threshold BD (hazard ratio = 6.9, p < .05) above and beyond the fourteen-fold increase in risk related to major depressive episodes (MDEs) per se (hazard ratio = 13.9, p < .05). Individual depressive features predicting conversion were psychomotor retardation and ⩾5 MDEs. Behavioural disorders only predicted conversion to subthreshold BD (hazard ratio = 5.23, p < .01), while anxiety and substance disorders did not predict either threshold or subthreshold hypo/mania.


This study suggests that specific depressive characteristics substantially increase the risk of young people at familial risk of BD going on to develop future hypo/manic episodes and may identify a more targeted HR population for the development of early intervention programs.


Corresponding author

Author for correspondence: Philip B. Mitchell, E-mail:


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Clinical predictors of conversion to bipolar disorder in a prospective longitudinal familial high-risk sample: focus on depressive features

  • Andrew Frankland (a1) (a2), Gloria Roberts (a1) (a2), Ellen Holmes-Preston (a1) (a2), Tania Perich (a1) (a2) (a3), Florence Levy (a1) (a4), Rhoshel Lenroot (a1) (a5), Dusan Hadzi-Pavlovic (a1) (a2), Michael Breakspear (a1) (a6) and Philip B. Mitchell (a1) (a2)...


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