TY - JOUR
T1 - What is familial about familial bipolar disorder? Resemblance among relatives across a broad spectrum of phenotypic characteristics
AU - Schulze, Thomas G.
AU - Hedeker, Donald
AU - Zandi, Peter
AU - Rietschel, Marcella
AU - McMahon, Francis Joseph
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/12
Y1 - 2006/12
N2 - Context: Current diagnostic criteria for bipolar affective disorder define a phenotype that is highly heritable, yet clinically variable. A more homogeneous definition might facilitate genetic and other studies, but the best approach is unclear. Familial features of bipolar disorder should help define more homogeneous subtypes, but there are few data indicating which clinical features of bipolar disorder are the most familial. Objective: To study the familiality of phenotypic features in families ascertained through individuals with bipolar affective disorder. Design: The study comprises 1246 individuals in 172 multiplex families ascertained for genetic linkage studies of bipolar disorder. The familiality of 40 diverse phenotypic features was studied using mixed-effects regression analysis. Results: Substance abuse, alcoholism, psychosis, history of suicide attempt, and the level of social functioning were all strongly familial in this sample. Several other traits, including clinical subtype, earliest age at onset, and comorbid panic disorder, showed a suggestion of familiality that did not hold up to conservative correction for multiple testing. Conclusions: This is the largest and most comprehensive study to assess the familiality of phenotypic features in bipolar disorder. Our results suggest that comorbid conditions and social functioning should be considered along with other familial clinical features in formulating subtypes of bipolar disorder suitable for further studies. Familial variables may help reduce diagnostic heterogeneity in genetic and other biological studies.
AB - Context: Current diagnostic criteria for bipolar affective disorder define a phenotype that is highly heritable, yet clinically variable. A more homogeneous definition might facilitate genetic and other studies, but the best approach is unclear. Familial features of bipolar disorder should help define more homogeneous subtypes, but there are few data indicating which clinical features of bipolar disorder are the most familial. Objective: To study the familiality of phenotypic features in families ascertained through individuals with bipolar affective disorder. Design: The study comprises 1246 individuals in 172 multiplex families ascertained for genetic linkage studies of bipolar disorder. The familiality of 40 diverse phenotypic features was studied using mixed-effects regression analysis. Results: Substance abuse, alcoholism, psychosis, history of suicide attempt, and the level of social functioning were all strongly familial in this sample. Several other traits, including clinical subtype, earliest age at onset, and comorbid panic disorder, showed a suggestion of familiality that did not hold up to conservative correction for multiple testing. Conclusions: This is the largest and most comprehensive study to assess the familiality of phenotypic features in bipolar disorder. Our results suggest that comorbid conditions and social functioning should be considered along with other familial clinical features in formulating subtypes of bipolar disorder suitable for further studies. Familial variables may help reduce diagnostic heterogeneity in genetic and other biological studies.
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U2 - 10.1001/archpsyc.63.12.1368
DO - 10.1001/archpsyc.63.12.1368
M3 - Article
C2 - 17146011
AN - SCOPUS:33845348623
SN - 0003-990X
VL - 63
SP - 1368
EP - 1376
JO - Archives of general psychiatry
JF - Archives of general psychiatry
IS - 12
ER -