Neurocognitive endophenotypes for bipolar disorder identified in multiplex multigenerational families.
BACKGROUND
Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, a strategy for identifying risk genes is to identify and map quantitative intermediate phenotypes or endophenotypes.


OBJECTIVE
To adjudicate neurocognitive endophenotypes for bipolar disorder.


METHODS
All participants underwent diagnostic interviews and comprehensive neurocognitive evaluations. Neurocognitive measures found to be heritable were entered into analyses designed to determine which test results are impaired in affected individuals, are sensitive to the genetic liability for the illness, and are genetically correlated with affection status.


METHODS
Central valley of Costa Rica; Mexico City, Mexico; and San Antonio, Texas.


METHODS
Seven hundred nine Latino individuals participated in the study. Of these, 660 were members of extended pedigrees with at least 2 siblings diagnosed as having bipolar disorder (n = 230). The remaining subjects were community control subjects drawn from each site who did not have a personal or family history of bipolar disorder or schizophrenia.


METHODS
Neurocognitive test performance.


RESULTS
Two of the 22 neurocognitive variables were not significantly heritable and were excluded from subsequent analyses. Patients with bipolar disorder were impaired on 6 cognitive measures compared with nonrelated healthy controls. Nonbipolar first-degree relatives were impaired on 5 of these, and the following 3 tests were genetically correlated with affection status: Digit Symbol Coding Task, Object Delayed Response Task, and immediate facial memory.


CONCLUSIONS
This large-scale extended pedigree study of cognitive functioning in bipolar disorder identifies measures of processing speed, working memory, and declarative (facial) memory as candidate endophenotypes for bipolar disorder.
Glahn
David C
DC
Olin Neuropsychiatry Research Center, Whitehall Research Building, Institute of Living, Hartford, CT 06106, USA. david.glahn@yale.edu
Almasy
Laura
L
Barguil
Marcela
M
Hare
Elizabeth
E
Peralta
Juan Manuel
JM
Kent
Jack W
JW
Dassori
Albana
A
Contreras
Javier
J
Pacheco
Adriana
A
Lanzagorta
Nuria
N
Nicolini
Humberto
H
Raventós
Henriette
H
Escamilla
Michael A
MA
D000328:Adult; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D001008:Anxiety Disorders / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology*; D003072:Cognition Disorders / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D015897:Comorbidity; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005145:Face; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010375:Pedigree; D010641:Phenotype; D021641:Recognition, Psychology; D012931:Social Environment