Neuregulin-1 and the P300 waveform--a preliminary association study using a psychosis endophenotype.
OBJECTIVE
Neuregulin-1 (NRG1) has been put forward as a susceptibility gene for schizophrenia. We investigated the association between Neuregulin-1 and the P300 wave, a schizophrenia endophenotype.


METHODS
Participants were 64 patients with DSM-IV schizophrenia or schizoaffective disorder, 97 of their non psychotic relatives and 35 unrelated controls. The P300 wave was extracted from the electroencephalogram whilst the subjects conducted a two-tone discrimination task. The effect of three markers from the core NRG-1 at-risk haplotype including single nucleotide polymorphism SNP8NRG221533 and two microsatellites (478B14-848 and 420M9-1395) on P300 amplitude and latency was examined using multilevel modelling.


RESULTS
Neuregulin-1 SNP8NRG221533 had a significant influence on P300 latency and the higher the number of C alleles carried, the greater the latency delay [Coef.=32.4 ms; 95%CI: 13.2 to 51.6 ms; p=0.001]. There was no association between latency and NRG1 microsatellites or between amplitude and any of the three markers examined.


CONCLUSIONS
The P300 latency reflects the speed of neural transmission. We hypothesise that variation in NRG1 may convey risk for schizophrenia by disrupting neural connectivity, possibly white matter integrity, and leading to a slower speed of cognitive processing. This is a preliminary finding in a small sample and requires replication.
Institute of Psychiatry-King's College London, Division of Psychological Medicine and Psychiatry (box 63), De Crespigny Park, London SE5 8AF, United Kingdom. elvira.bramon@iop.kcl.ac.uk
Elvira
E
Bramon
Emma
E
Dempster
Sophia
S
Frangou
Madiha
M
Shaikh
Muriel
M
Walshe
Francesca M
FM
Filbey
Colm
C
McDonald
Pak
P
Sham
David A
DA
Collier
Robin
R
Murray
D000483:Alleles; D002540:Cerebral Cortex / Q000503:physiopathology; D004569:Electroencephalography; D018913:Event-Related Potentials, P300 / Q000235:genetics* / Q000502:physiology; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D010641:Phenotype; D010897:Pitch Discrimination / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D011930:Reaction Time / Q000235:genetics / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1