The clinical staging model proposed represents an aggregate view based on results from an ongoing, prospective study of a unique, high-risk cohort. In prior analyses, we found evidence that ADHD and other childhood neurodevelopmental presentations occurred at a higher unadjusted rate in the offspring of parents with lithium-non-responsive illness compared with the offspring of parents with lithium-responsive illness.Reference Duffy, Alda, Hajek, Sherry and Grof1,Reference Duffy, Alda, Crawford, Milin and Grof2 In this updated analysis, instead of unadjusted lifetime rates we used cumulative incidence, which takes into account censoring and variable age at last assessment and Cox proportional hazard models adjusted for sibling correlation, gender and socioeconomic status. With longer observation, the unadjusted rate of psychotic disorders is now significantly elevated in the offspring of parents with lithium-non-responsive illness compared with the offspring of parents with lithium-responsive illness.
Second, cluster A traits and cognitive deficits are known antecedents to psychotic disorders and therefore we argue that these do in fact ‘fit’ with ADHD and learning disabilities as early risk syndromes in this high-risk population.Reference Murray, Sham, Van Os, Zanelli, Cannon and McDonald3 Third, schizo-affective disorder was included as an end-stage illness in this analysis given the overlap between schizoaffective and psychotic bipolar disorders.Reference Pearlson and Ford4 Fourth, all offspring (control and high-risk) were assessed in the same way and all assessments were reviewed masked to family affiliation and diagnoses made by consensus using the same criteria. Therefore, the difference in rates of bipolar disorder not otherwise specified or any other diagnosis cannot be explained by modified diagnostic criteria for high-risk offspring as speculated by Chenard-Poirier & Paris.
Finally, given the high heritability and estimated likelihood that recurrent major depression in these families reflects the bipolar diathesis,Reference Blacker, Lavori, Faraone and Tsuang5 we expanded recruitment to include the offspring of parents who were siblings of the original bipolar proband and who themselves met lifetime criteria for bipolar disorder or recurrent major depression (n = 20). Therefore, every high-risk offspring had one parent with a bipolar or bipolar-related recurrent major depressive disorder. We thank Chenard-Poirier & Paris for raising these points and the Journal for allowing us to provide this clarification.
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