PMID- 21281445
OWN - NLM
STAT- MEDLINE
DCOM- 20111007
LR  - 20130213
IS  - 1601-183X (Electronic)
IS  - 1601-183X (Linking)
VI  - 10
IP  - 4
DP  - 2011 Jun
TI  - Polymorphisms associated with normal memory variation also affect memory 
      impairment in schizophrenia.
PG  - 410-7
LID - 10.1111/j.1601-183X.2011.00679.x [doi]
AB  - Neurocognitive dysfunction is a core feature of schizophrenia with particularly 
      prominent deficits in verbal episodic memory. The molecular basis of this memory 
      impairment is poorly understood and its relatedness to normal variation in memory 
      performance is unclear. In this study, we explore, in a sample of cognitively 
      impaired schizophrenia patients, the role of polymorphisms in seven genes 
      recently reported to modulate episodic memory in normal subjects. Three 
      polymorphisms (GRIN2B rs220599, GRM3 rs2189814 and PRKCA rs8074995) were 
      associated with episodic verbal memory in both control and patients with 
      cognitive deficit, but not in cognitively spared patients or the pooled 
      schizophrenia sample. GRM3 and PRKCA acted in opposite directions in patients 
      compared to controls, possibly reflecting an abnormal brain milieu and/or adverse 
      environmental effects in schizophrenia. The encoded proteins balance glutamate 
      signalling vs. excitotoxicity in complex interactions involving the excitatory 
      amino acid transporter 2 (EAAT2), implicated in the dysfunctional glutamatergic 
      signalling in schizophrenia. Double carrier status of the GRM3 and PRKCA minor 
      alleles was associated with lower memory test scores and with increased risk of 
      schizophrenia. Single nucleotide polymorphism (SNP) rs8074995 lies within the 
      PRKCA region spanned by a rare haplotype associated with schizophrenia in a 
      recent UK study and provides further evidence of PRKCA contribution to memory 
      impairment and susceptibility to schizophrenia. Our study supports the utility of 
      parsing the broad phenotype of schizophrenia into component cognitive 
      endophenotypes that reduce heterogeneity and enable the capture of potentially 
      important genetic associations.
CI  - (c) 2011 The Authors. Genes, Brain and Behavior (c) 2011 Blackwell Publishing Ltd and 
      International Behavioural and Neural Genetics Society.
FAU - Jablensky, A
AU  - Jablensky A
AD  - Centre for Clinical Research in Neuropsychiatry and School of Psychiatry and 
      Clinical Neurosciences, University of Western Australia, Perth, Australia. 
      assen@cyllene.uwa.edu.au
FAU - Morar, B
AU  - Morar B
FAU - Wiltshire, S
AU  - Wiltshire S
FAU - Carter, K
AU  - Carter K
FAU - Dragovic, M
AU  - Dragovic M
FAU - Badcock, J C
AU  - Badcock JC
FAU - Chandler, D
AU  - Chandler D
FAU - Peters, K
AU  - Peters K
FAU - Kalaydjieva, L
AU  - Kalaydjieva L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110210
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (metabotropic glutamate receptor 3)
RN  - EC 2.7.11.13 (PRKCA protein, human)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
SB  - IM
MH  - Alleles
MH  - Endophenotypes
MH  - Genotype
MH  - Haplotypes
MH  - Humans
MH  - Memory/*physiology
MH  - Memory Disorders/*genetics
MH  - Neuropsychological Tests
MH  - Phenotype
MH  - *Polymorphism, Genetic
MH  - Protein Kinase C-alpha/genetics
MH  - Receptors, Metabotropic Glutamate/genetics
MH  - Receptors, N-Methyl-D-Aspartate/genetics
MH  - Schizophrenia/*genetics
MH  - Schizophrenic Psychology
EDAT- 2011/02/02 06:00
MHDA- 2011/10/08 06:00
CRDT- 2011/02/02 06:00
PHST- 2011/02/02 06:00 [entrez]
PHST- 2011/02/02 06:00 [pubmed]
PHST- 2011/10/08 06:00 [medline]
AID - 10.1111/j.1601-183X.2011.00679.x [doi]
PST - ppublish
SO  - Genes Brain Behav. 2011 Jun;10(4):410-7. doi: 10.1111/j.1601-183X.2011.00679.x. 
      Epub 2011 Feb 10.