Journal
MOLECULAR PSYCHIATRY
Volume 6, Issue 3, Pages 311-314Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.mp.4000848
Keywords
metabotropic; glutamate; GRM5; mGluR5; schizophrenia; association
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The G-protein coupled metabotropic glutamate receptors (GRMs/mGluRs) have been implicated in the aetiology of schizophrenia as they modulate the NMDA response and that of other neurotransmitters including dopamine and GABA.(1-3) Electrophysiological studies in GRM subtype 5 knockout mice reveal, in one study, a sensorimotor gating deficit characteristic of schizophrenia(4) and in another, a key role for this gene in the modulation of hippocampal NMDA-dependent synaptic plasticity.(5) In humans, GRM5 levels are increased in certain pyramidal cell neurons in schizophrenics vs controls.(6) Finally, GRM5 has been mapped to 11q14, neighbouring a translocation that segregates with schizophrenia and related psychoses in a large Scottish family, F23 (MLOD score 6.0).(7,8) We determined the intron/exon structure of GRM5 and identified a novel intragenic microsatellite. A case-control association study identified a significant difference in allele frequency distribution between schizophrenics and controls (P = 0.04). This is suggestive of involvement of the GRM5 gene in schizophrenia in this population.
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