Do COMT, BDNF and NRG1 polymorphisms influence P50 sensory gating in psychosis?

Shaikh, Madiha; Hall, Mei‐Hua; Schulze, Katja; Dutt, Aparna; Walshe, Muriel; Williams, Ian; Constante, Miguel; Picchioni, Marco; Toulopoulou, Timothea; Collier, David; Rijsdijk, Frühling; Powell, John; Arranz, Maria; Murray, Robin M.; Bramon, Elvira

doi:10.1017/s003329170999239x

Cited by 36 publications

(33 citation statements)

References 128 publications

(218 reference statements)

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“…Lu et al (2007) reported that Val homozygotes exhibited greater gating deficits in both SZ patients and controls. Shaikh et al (2011) found no association between Val158Met and P50 gating in SZ patients, first-degree relatives, and controls. Majic et al (2011) also reported that P50 gating was not affected by COMT genotype in healthy controls.…”

Section: Introductionmentioning

confidence: 62%

“…The other two studies involving P50 sensory gating and the COMT Val158Met polymorphism found no association in both a large sample consisting of SZ patients (n=138), first-degree relatives (n=109) and healthy subjects (n=204) (Shaikh et al, 2011) and a sample of healthy controls (n=282) (Majic et al, 2011). However, the methodology of these studies varied greatly with regard to the study sample, P50 paradigm and recording, as well as ERP processing.…”

Section: Comparison With Previous Findingsmentioning

confidence: 99%

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Effects of COMT genotype on sensory gating and its modulation by nicotine: Differences in low and high P50 suppressors

et al. 2013

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Elevated smoking rates seen in schizophrenia populations may be an attempt to correct neuropathologies associated with deficient nicotinic acetylcholine receptors and/or dopaminergic systems using exogenous nicotine. However, nicotine's effects on cognitive processing and sensory gating have been shown to be baseline-dependent. Evidence of a restorative effect on sensory gating deficits by nicotine-like agonists has been demonstrated, however, its underlying mechanisms in the context of dopamine dysregulation are unclear. Catechol-O-methyltransferase (COMT), a key dopamine regulator in the brain, contains a co-dominant allele in which a valineto-methionine substitution causes variations in enzymatic activity leading to reduced synaptic dopamine levels in the Val/Val genotype. Using a randomized, double-blind, placebo-controlled design with 57 non-smokers, this study examined the effects of COMT genotype on sensory gating and its modulation by nicotine in low vs. high suppressors. The results were consistent with the hypothesis that increased dopamine resulting from nicotine stimulation or Met allelic activity would benefit gating in low suppressors and impair gating in high suppressors, and that this gating improvement with nicotine would be more evident in Val carriers who were low suppressors, while the gating impairment would be more evident in Met carriers who were high suppressors. These findings reaffirm the importance of baseline-dependency and suggest a subtle relationship between COMT genotype and baseline-stratified levels of sensory gating, which may help to explain the variability of cognitive abilities in schizophrenia populations.

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Section: Introductionmentioning

confidence: 62%

Section: Comparison With Previous Findingsmentioning

confidence: 99%

Effects of COMT genotype on sensory gating and its modulation by nicotine: Differences in low and high P50 suppressors

et al. 2013

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“…[30][31][32] The P50 wave is generated in a conditioning-testing paradigm where the first stimulus activates or conditions the inhibition phenomenon, whereas the second tests its strength. Normally, individuals reduce the second (test) response relative to the first (condition) waves.…”

Section: Introductionmentioning

confidence: 99%

“…1,[33][34][35] Compared with controls, patients with schizophrenia and psychotic bipolar disorder have a relatively larger P50 response to the second stimulus, from only 20-50% suppression. 31,[36][37][38][39][40][41][42][43][44][45][46][47] Clinically unaffected first-degree relatives of patients with schizophrenia and psychotic bipolar disorder also have poor P50 suppression, suggesting that this might act as a marker of genetic risk for these disorders, [46][47][48][49][50][51][52][53] as it is heritable. [54][55][56][57] We have examined the effects of CHRFAM7A CNV/2 bp deletion variants on the major psychoses and the P50 sensory gating deficit.…”

Section: Introductionmentioning

confidence: 99%

Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

et al. 2012

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There is considerable evidence implicating the 15q13.3 region in neuropsychiatric disorders, with the a7 nicotinic receptor gene CHRNA7 the most plausible candidate. This region has multiple duplications and many copy number variants (CNVs). A common CNV involves a partial duplication of CHRNA7 (CHRFAM7A), which occurs in either orientation. We examined the distribution of these alternative genomic arrangements in a large cohort of psychiatric patients, their relatives and controls using the 2-bp deletion polymorphism as a marker for the orientation of CHRFAM7A. We investigated three common alleles for association with psychosis and with the P50 sensory gating deficit, which is strongly associated with psychosis and strongly linked to 15q13.3. We found significant within-family association with P50 (empirical P ¼ 0.004), which is robust to population stratification. Most of the effect came from the 2-bp deletion allele, which tags the variant of CHRFAM7A in the same orientation as CHRNA7. This allele is associated with the presence of the P50 sensory gating deficit (empirical P ¼ 0.0006). Tests comparing within-family and between-family components of association suggest considerable population stratification in the sample. We found no evidence for association with psychosis, but this may reflect lower power using this phenotype. Four out of six previous association studies found association of different psychiatric phenotypes with the same 2-bp deletion allele.

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“…These genes are mostly involved in dopaminergic, nicotinic and glutamatergic mechanisms. For example, P50 gating deficits have been linked to the alpha-7 nicotinic acetylcholine receptor as well as the Catechol-O-methyltransferase (COMT) genes (Lu et al, 2007), although the later result was not replicated in a recent study (Shaikh et al, , Freedman et al, 1997, Shaikh et al, 2011. Also, P300 amplitude decrease is associated with COMT and Disrupted in schizophrenia-1 (DISC1) genes while P300 increased latency is significantly influenced by the dopamine D2/D3 receptor as well as the Neuregulin-1 (NRG1) genes (Hill et al, 1998, Anokhin et al, 1999, Blackwood et al, 2001, Gallinat et al, 2003, Blackwood and Muir, 2004, Berman et al, 2006, Mulert et al, 2006, Bramon et al, 2008.…”

Section: Transgenic Approachesmentioning

confidence: 99%

Electrophysiological Deficits in Schizophrenia: Models and Mechanisms

Jutzeler¹,

McMullen²,

Featherstone³

et al. 2011

Psychiatric Disorders - Trends and Developments

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Do COMT, BDNF and NRG1 polymorphisms influence P50 sensory gating in psychosis?

Abstract: The evidence from our large study suggests that any such association between P50 indices and NRG1, COMT Val158Met or BDNF Val66Met genotypes, if present, must be very subtle.

Cited by 36 publications

References 128 publications

Effects of COMT genotype on sensory gating and its modulation by nicotine: Differences in low and high P50 suppressors

Effects of COMT genotype on sensory gating and its modulation by nicotine: Differences in low and high P50 suppressors

Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

Electrophysiological Deficits in Schizophrenia: Models and Mechanisms

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