Verbal working memory impairments in individuals with schizophrenia and their first-degree relatives: findings from the Consortium on the Genetics of Schizophrenia.
Working memory (WM) impairment is a promising candidate endophenotype for schizophrenia that could facilitate the identification of susceptibility genes for this disorder. The validity of this putative endophenotype was assessed by determining whether 149 probands with schizophrenia and 337 of their first-degree relatives demonstrated WM impairment as compared to 190 unaffected community comparison subjects. Subjects were participants in the Consortium on the Genetics of Schizophrenia (COGS) project, a seven-site research network that was established to investigate the genetic architecture of endophenotypes for schizophrenia. Participants received comprehensive clinical assessments and completed two verbal WM tasks, one requiring transient on-line storage and another requiring maintenance plus complex manipulation of information by reordering the stimuli. Schizophrenia probands performed worse than the other groups on both tasks, with larger deficits found for the more challenging reordering WM task. The probands' relatives performed more poorly than community comparison subjects on both tasks, but the difference was significant only for the more challenging maintenance plus complex manipulation WM task. This WM impairment was not attributable to diagnoses of schizophrenia spectrum disorder, mood disorders, or substance use disorders in the relatives. In conjunction with evidence that WM abilities are substantially heritable, the current results support the validity and usefulness of verbal WM impairments in manipulation of information as endophenotypes for schizophrenia in large-scale genetic linkage and association studies.
Horan
William P
WP
Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095-6968, USA. horan@ucla.edu
Braff
David L
DL
Nuechterlein
Keith H
KH
Sugar
Catherine A
CA
Cadenhead
Kristin S
KS
Calkins
Monica E
ME
Dobie
Dorcas J
DJ
Freedman
Robert
R
Greenwood
Tiffany A
TA
Gur
Raquel E
RE
Gur
Ruben C
RC
Light
Gregory A
GA
Mintz
James
J
Olincy
Ann
A
Radant
Allan D
AD
Schork
Nicholas J
NJ
Seidman
Larry J
LJ
Siever
Larry J
LJ
Silverman
Jeremy M
JM
Stone
William S
WS
Swerdlow
Neal R
NR
Tsuang
Debbie W
DW
Tsuang
Ming T
MT
Turetsky
Bruce I
BI
Green
Michael F
MF
D000328:Adult; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010641:Phenotype; D011594:Psychometrics; D012016:Reference Values; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012691:Serial Learning; D014706:Verbal Learning