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Effect of DISC1 on the P300 waveform in psychosis.

ABSTRACT: Abnormalities in the neurophysiological measures P300 amplitude and latency constitute endophenotypes for psychosis. Disrupted-in-Schizophrenia-1 (DISC1) has been proposed as a promising susceptibility gene for schizophrenia, and a previous study has suggested that it is associated with P300 deficits in schizophrenia.We examined the role of variation in DISC1 polymorphisms on the P300 endophenotype in a large sample of patients with schizophrenia or psychotic bipolar disorder (n = 149), their unaffected relatives (n = 130), and unrelated healthy controls (n = 208) using linear regression and haplotype analysis.Significant associations between P300 amplitude and latency and DISC1 polymorphisms/haplotypes were found. Those homozygous for the A allele of single-nucleotide polymorphism (SNP) rs821597 displayed significantly reduced P300 amplitudes in comparison with homozygous for the G allele (P = .009) and the heterozygous group (P = .018). Haplotype analysis showed a significant association for DISC1 haplotypes (rs3738401|rs6675281|rs821597|rs821616|rs967244|rs980989) and P300 latency. Haplotype GCGTCG and ACGTTT were associated with shorter latencies.The P300 waveform appears to be modulated by variation in individual SNPs and haplotypes of DISC1. Because DISC1 is involved in neurodevelopment, one hypothesis is that disruption in neural connectivity impairs cognitive processes illustrated by P300 deficits observed in this sample.

SUBMITTER: Shaikh M

PROVIDER: S-EPMC3523903 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Effect of DISC1 on the P300 waveform in psychosis.

Shaikh Madiha M Hall Mei-Hua MH Schulze Katja K Dutt Anirban A Li Kuang K Williams Ian I Walshe Muriel M Walshe Muriel M Constante Miguel M Broome Matthew M Picchioni Marco M Toulopoulou Timothea T Collier David D Stahl Daniel D Rijsdijk Fruhling F Powell John J Murray Robin M RM Arranz Maria M Bramon Elvira E

Schizophrenia bulletin 20110830 1

<h4>Introduction</h4>Abnormalities in the neurophysiological measures P300 amplitude and latency constitute endophenotypes for psychosis. Disrupted-in-Schizophrenia-1 (DISC1) has been proposed as a promising susceptibility gene for schizophrenia, and a previous study has suggested that it is associated with P300 deficits in schizophrenia.<h4>Methods</h4>We examined the role of variation in DISC1 polymorphisms on the P300 endophenotype in a large sample of patients with schizophrenia or psychotic ...[more]

PMID: 21878470

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Project description:BackgroundSchizophrenia often occurs in youth, and psychosis risk syndrome (PRS) occurs before the onset of psychosis. Assessing the neuropsychological abnormalities of PRS individuals can help in early identification and active intervention of mental illness. Auditory P300 amplitude defect is an important manifestation of attention processing abnormality in PRS, but it is still unclear whether there are abnormalities in the attention processing of rhythmic compound tone stimuli in PRS individuals, and whether the P300 amplitude induced by these stimuli is specific to PRS individuals and related to their clinical outcomes.MethodsIn total, 226 participants, including 122 patients with PRS, 51 patients with emotional disorders (ED), and 53 healthy controls (HC) were assessed. Baseline electroencephalography was recorded during the compound tone oddball task. The event-related potentials (ERPs) induced by rhythmic compound tone stimuli of two frequencies (20-Hz, 40-Hz) were measured. Almost all patients with PRS were followed up for 12 months and reclassified into four groups: PRS-conversion, PRS-symptomatic, PRS-emotional disorder, and PRS-complete remission. The differences in baseline ERPs were compared among the clinical outcome groups.ResultsRegardless of the stimulation frequency, the average P300 amplitude were significantly higher in patients with PRS than in those with ED (p = 0.003, d = 0.48) and in HC (p = 0.002, d = 0.44) group. The average P300 amplitude of PRS-conversion group was significantly higher than that of the PRS-complete remission (p = 0.016, d = 0.72) and HC group (p = 0.001, d = 0.76), and the average P300 amplitude of PRS-symptomatic group was significantly higher than that of the HC group (p = 0.006, d = 0.48). Regardless of the groups (PRS, ED, HC) or the PRS clinical outcome groups, the average P300 amplitude induced by 20-Hz tone stimulation was significantly higher than that induced by 40-Hz stimulation (ps < 0.001, Ƞ2 = 0.074-0.082). The average reaction times of PRS was significantly faster than that of ED (p = 0.01, d = 0.38), and the average reaction times of the participants to 20-Hz target stimulation was significantly faster than that to 40-Hz target stimulation (p < 0.001, d = 0.21).ConclusionThe auditory P300 amplitude induced by rhythmic compound tone stimuli is a specific electrophysiological manifestation of PRS, and the auditory P300 amplitude induced by compound tone stimuli shows promise as a putative prognostic biomarker for PRS clinical outcomes, including conversion to psychosis and clinical complete remission.

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Effect of DISC1 on the P300 waveform in psychosis.

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Effect of DISC1 on the P300 waveform in psychosis.

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