Mood-incongruent psychotic features in bipolar disorder: Familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33

Fernando S. Goes, Peter P. Zandi, Kuangyi Miao, Francis J. McMahon, Jo Steele, Virginia L. Willour, Dean F. MacKinnon, Francis M. Mondimore, Barbara Schweizer, John Nurnberger, John P. Rice, William Scheftner, William Coryell, Wade H. Berrettini, John R. Kelsoe, William Byerley, Dennis L. Murphy, Elliot S. Gershon, J. Raymond DePaulo, Melvin G. McInnisJames B. Potash

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Objective: Mood-incongruent psychotic features in bipolar disorder may signify a more severe form of the illness and might represent phenotypic manifestations of susceptibility genes shared with schizophrenia. This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features. Method: Subjects were drawn from The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative cohort, consisting of 708 families recruited at 10 academic medical centers. Subjects with mood-incongruent and mood-congruent psychotic features were compared on clinical variables. Familial aggregation was tested using a proband-predictive model and generalized estimating equations. A genome-wide linkage scan incorporating a mood-incongruence covariate was performed. Results: Mood-incongruent psychotic features were associated with an increased rate of hospitalization and attempted suicide. A proband with mood-incongruence predicted mood-incongruence in relatives with bipolar I disorder when compared with all other subjects and when compared with subjects with mood-congruent psychosis. The presence of mood-incongruent psychotic features increased evidence for linkage on chromosomes 13q21-33 and 2p11-q14. These logarithm of the odds ratio (LOD) scores and their increase from baseline met empirical genome-wide suggestive criteria for significance. Conclusions: Mood-incongruent psychotic features showed evidence of a more severe course, familial aggregation, and suggestive linkage to two chromosomal regions previously implicated in major mental illness susceptibility. The 13q21-33 finding supports prior evidence of bipolar disorder/schizophrenia overlap in this region, while the 2p11-q14 finding is, to the authors' knowledge, the first to suggest that this schizophrenia linkage region might also harbor a bipolar disorder susceptibility gene.

Original languageEnglish (US)
Pages (from-to)236-247
Number of pages12
JournalAmerican Journal of Psychiatry
Volume164
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

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Bipolar Disorder
Schizophrenia
Genome
National Institute of Mental Health (U.S.)
Attempted Suicide
Genetic Linkage
Psychotic Disorders
Genes
Hospitalization
Chromosomes
Odds Ratio

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Mood-incongruent psychotic features in bipolar disorder : Familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33. / Goes, Fernando S.; Zandi, Peter P.; Miao, Kuangyi; McMahon, Francis J.; Steele, Jo; Willour, Virginia L.; MacKinnon, Dean F.; Mondimore, Francis M.; Schweizer, Barbara; Nurnberger, John; Rice, John P.; Scheftner, William; Coryell, William; Berrettini, Wade H.; Kelsoe, John R.; Byerley, William; Murphy, Dennis L.; Gershon, Elliot S.; DePaulo, J. Raymond; McInnis, Melvin G.; Potash, James B.

In: American Journal of Psychiatry, Vol. 164, No. 2, 02.2007, p. 236-247.

Research output: Contribution to journalArticle

Goes, FS, Zandi, PP, Miao, K, McMahon, FJ, Steele, J, Willour, VL, MacKinnon, DF, Mondimore, FM, Schweizer, B, Nurnberger, J, Rice, JP, Scheftner, W, Coryell, W, Berrettini, WH, Kelsoe, JR, Byerley, W, Murphy, DL, Gershon, ES, DePaulo, JR, McInnis, MG & Potash, JB 2007, 'Mood-incongruent psychotic features in bipolar disorder: Familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33', American Journal of Psychiatry, vol. 164, no. 2, pp. 236-247. https://doi.org/10.1176/appi.ajp.164.2.236
Goes, Fernando S. ; Zandi, Peter P. ; Miao, Kuangyi ; McMahon, Francis J. ; Steele, Jo ; Willour, Virginia L. ; MacKinnon, Dean F. ; Mondimore, Francis M. ; Schweizer, Barbara ; Nurnberger, John ; Rice, John P. ; Scheftner, William ; Coryell, William ; Berrettini, Wade H. ; Kelsoe, John R. ; Byerley, William ; Murphy, Dennis L. ; Gershon, Elliot S. ; DePaulo, J. Raymond ; McInnis, Melvin G. ; Potash, James B. / Mood-incongruent psychotic features in bipolar disorder : Familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33. In: American Journal of Psychiatry. 2007 ; Vol. 164, No. 2. pp. 236-247.
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abstract = "Objective: Mood-incongruent psychotic features in bipolar disorder may signify a more severe form of the illness and might represent phenotypic manifestations of susceptibility genes shared with schizophrenia. This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features. Method: Subjects were drawn from The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative cohort, consisting of 708 families recruited at 10 academic medical centers. Subjects with mood-incongruent and mood-congruent psychotic features were compared on clinical variables. Familial aggregation was tested using a proband-predictive model and generalized estimating equations. A genome-wide linkage scan incorporating a mood-incongruence covariate was performed. Results: Mood-incongruent psychotic features were associated with an increased rate of hospitalization and attempted suicide. A proband with mood-incongruence predicted mood-incongruence in relatives with bipolar I disorder when compared with all other subjects and when compared with subjects with mood-congruent psychosis. The presence of mood-incongruent psychotic features increased evidence for linkage on chromosomes 13q21-33 and 2p11-q14. These logarithm of the odds ratio (LOD) scores and their increase from baseline met empirical genome-wide suggestive criteria for significance. Conclusions: Mood-incongruent psychotic features showed evidence of a more severe course, familial aggregation, and suggestive linkage to two chromosomal regions previously implicated in major mental illness susceptibility. The 13q21-33 finding supports prior evidence of bipolar disorder/schizophrenia overlap in this region, while the 2p11-q14 finding is, to the authors' knowledge, the first to suggest that this schizophrenia linkage region might also harbor a bipolar disorder susceptibility gene.",
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AU - Goes, Fernando S.

AU - Zandi, Peter P.

AU - Miao, Kuangyi

AU - McMahon, Francis J.

AU - Steele, Jo

AU - Willour, Virginia L.

AU - MacKinnon, Dean F.

AU - Mondimore, Francis M.

AU - Schweizer, Barbara

AU - Nurnberger, John

AU - Rice, John P.

AU - Scheftner, William

AU - Coryell, William

AU - Berrettini, Wade H.

AU - Kelsoe, John R.

AU - Byerley, William

AU - Murphy, Dennis L.

AU - Gershon, Elliot S.

AU - DePaulo, J. Raymond

AU - McInnis, Melvin G.

AU - Potash, James B.

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N2 - Objective: Mood-incongruent psychotic features in bipolar disorder may signify a more severe form of the illness and might represent phenotypic manifestations of susceptibility genes shared with schizophrenia. This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features. Method: Subjects were drawn from The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative cohort, consisting of 708 families recruited at 10 academic medical centers. Subjects with mood-incongruent and mood-congruent psychotic features were compared on clinical variables. Familial aggregation was tested using a proband-predictive model and generalized estimating equations. A genome-wide linkage scan incorporating a mood-incongruence covariate was performed. Results: Mood-incongruent psychotic features were associated with an increased rate of hospitalization and attempted suicide. A proband with mood-incongruence predicted mood-incongruence in relatives with bipolar I disorder when compared with all other subjects and when compared with subjects with mood-congruent psychosis. The presence of mood-incongruent psychotic features increased evidence for linkage on chromosomes 13q21-33 and 2p11-q14. These logarithm of the odds ratio (LOD) scores and their increase from baseline met empirical genome-wide suggestive criteria for significance. Conclusions: Mood-incongruent psychotic features showed evidence of a more severe course, familial aggregation, and suggestive linkage to two chromosomal regions previously implicated in major mental illness susceptibility. The 13q21-33 finding supports prior evidence of bipolar disorder/schizophrenia overlap in this region, while the 2p11-q14 finding is, to the authors' knowledge, the first to suggest that this schizophrenia linkage region might also harbor a bipolar disorder susceptibility gene.

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