Influence of NOS1 on Verbal Intelligence and Working Memory in Both Patients With Schizophrenia and Healthy Control Subjects

被引：43

作者：

Donohoe, Gary ^{[1
,2
,3
]}

Walters, James ^{[4
]}

Morris, Derek W. ^{[2
]}

Quinn, Emma M. ^{[2
]}

Judge, Roisin ^{[2
]}

Norton, Nadine ^{[4
]}

Giegling, Ina ^{[5
]}

Hartmann, Annette M. ^{[5
]}

Moeller, Hans-Juergen

Muglia, Pierandrea ^{[6
]}

Williams, Hywel ^{[4
]}

Moskvina, Valentina ^{[4
]}

Peel, Rosemary ^{[2
]}

O'Donoghue, Therese ^{[2
,3
]}

Owen, Michael J. ^{[4
]}

O'Donovan, Michael C. ^{[4
]}

Gill, Michael ^{[2
,3
]}

Rujescu, Dan ^{[5
]}

Corvin, Aiden ^{[2
,3
]}

机构：

[1] St James Hosp, Neuropsychiat Genet Res Grp, Dept Psychiat, Trinity Coll Dublin, Dublin 8, Ireland

[2] Univ Dublin Trinity Coll, Inst Mol Med, Dublin 2, Ireland

[3] Univ Dublin Trinity Coll, Trinity Inst Neurosci, Dublin 2, Ireland

[4] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales

[5] Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, D-8000 Munich, Germany

[6] GlaxoSmithKline, Med Genet, Res & Dev, Verona, Italy

来源：

ARCHIVES OF GENERAL PSYCHIATRY | 2009年 / 66卷 / 10期

基金：

爱尔兰科学基金会; 英国医学研究理事会; 英国惠康基金;

关键词：

NITRIC-OXIDE SYNTHASE; PREMORBID INTELLECTUAL-PERFORMANCE; PREPULSE INHIBITION; ALLELIC ASSOCIATION; SUSCEPTIBILITY LOCI; LOCOMOTOR-ACTIVITY; ACOUSTIC STARTLE; GENOME SCAN; L-NAME; PHENCYCLIDINE;

D O I：

10.1001/archgenpsychiatry.2009.139

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Context: Human and animal studies have implicated the gene NOS1 in both cognition and schizophrenia susceptibility. Objective: To investigate whether a potential schizophrenia risk single-nucleotide polymorphism (rs6490121) identified in a recent genome-wide association study negatively influences cognition in patients with schizophrenia and healthy control subjects. Design: A comparison of both cases and controls grouped according to NOS1 genotype (GG vs AG vs AA) on selected measures of cognition in 2 independent samples. We tested for association between NOS1 rs6490121 and cognitive functions known to be impaired in schizophrenia (IQ, episodic memory, working memory, and attentional control) in an Irish sample. We then sought to replicate the significant results in a German sample. Setting: Unrelated patients from general adult psychiatric inpatient and outpatient services and unrelated healthy volunteers from the general population were ascertained. Participants: Patients with DSM-IV-diagnosed schizophrenia and healthy control subjects from independent samples of Irish (cases, n = 349; controls, n = 230) and German (cases, n = 232; controls, n = 1344) nationality. Results: A main effect of NOS1 genotype on verbal IQ and working memory was observed in the Irish sample where the homozygous carriers of the schizophrenia risk Gallele performed poorly compared with the other genotype groups. These findings were replicated in the German sample, again with the GG genotype carriers performing below other genotype groups. Post hoc analysis of additional IQ measures (full-scale and performance IQ) in the German sample revealed that NOS1 GG carriers underperformed on these measures also. Conclusions: NOS1 is associated with clinically significant variation in cognition. Whether this is a mechanism by which schizophrenia risk is increased (eg, via an influence on cognitive reserve) is yet to be confirmed.

引用

页码：1045 / 1054

页数：10

共 97 条

[1] Predisposition locus for major depression at chromosome 12q22-12q23.2 [J].

Abkevich, V ;

Camp, NJ ;

Hensel, CH ;

Neff, CD ;

Russell, DL ;

Hughes, DC ;

Plenk, AM ;

Lowry, MR ;

Richards, RL ;

Carter, C ;

Frech, GC ;

Stone, S ;

Rowe, K ;

Chau, CA ;

Cortado, K ;

Hunt, A ;

Luce, K ;

O'Neil, G ;

Poarch, J ;

Potter, J ;

Poulsen, GH ;

Saxton, H ;

Bernat-Sestak, M ;

Thompson, V ;

Gutin, A ;

Skolnick, MH ;

Shattuck, D ;

Cannon-Albright, L .

AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (06) :1271-1281

[2]

AKBARIAN S, 1993, ARCH GEN PSYCHIAT, V50, P178

[3]

AKBARIAN S, 1993, ARCH GEN PSYCHIAT, V50, P169

[4]

ANDREASEN NC, 1989, BRITISH JOURNAL OF PSYCHIATRY, VOL 155, SUPP NO. 7, P49

[5]

[Anonymous], 1990, MINIMENTAL STATUS TE

[6]

[Anonymous], 3 7 CONTINUOUS PERFO

[7] Expression of nNOS and soluble guanylate cyclase in schizophrenic brain [J].

Baba, H ;

Suzuki, T ;

Arai, H ;

Emson, PC .

NEUROREPORT, 2004, 15 (04) :677-680

[8] BIND - The Biomolecular Interaction Network Database [J].

Bader, GD ;

Donaldson, I ;

Wolting, C ;

Ouellette, BFF ;

Pawson, T ;

Hogue, CWV .

NUCLEIC ACIDS RESEARCH, 2001, 29 (01) :242-245

[9] Genome scan for susceptibility loci for schizophrenia [J].

Bailer, U ;

Leisch, F ;

Meszaros, K ;

Lenzinger, E ;

Willinger, U ;

Strobl, R ;

Gebhardt, C ;

Gerhard, E ;

Fuchs, K ;

Sieghart, W ;

Kasper, S ;

Hornik, K ;

Aschauer, HN .

NEUROPSYCHOBIOLOGY, 2000, 42 (04) :175-182

[10] Genome scan for susceptibility loci for schizophrenia and bipolar disorder [J].