A meta-analysis of P50 studies in patients with schizophrenia and relatives: Differences in methodology between research groups

Wilde, O.M. de; Bour, L.J.; Dingemans, Peter; Koelman, J.H.T.M.; Linszen, D.H.

doi:10.1016/j.schres.2007.04.028

Cited by 144 publications

(137 citation statements)

References 43 publications

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“…Studies involving SZ patients have also found larger S 2 amplitudes (Clementz, 1998). The reduced ability to suppress the second stimulus in LS and Val/Val is consistent with the idea that there is a failure of inhibitory mechanisms (de Wilde et al, 2007), and these findings suggest that poorer levels of sensory gating stemming from failed S 2 inhibition "gating out" deficits, as opposed to a deficiency in responding to stimulus changes, or "gating in" mechanisms (Brenner et al, 2009), is associated with low PFC dopaminergic tone.…”

Section: Baseline-dependent Effects Of Genotype On Sensory Gatingsupporting

confidence: 72%

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: Baseline-dependent Effects Of Genotype On Sensory Gatingsupporting

confidence: 72%

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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“…Recent schizophrenia research has utilized the advantages of using pre‐attentive neurophysiological endophenotypes such as sensory gating in the ‘paired click’ paradigm (de Wilde et al . 2007, Light et al . 2012) or ASSR (Spencer et al .…”

Section: Discussionmentioning

confidence: 99%

The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia

et al. 2016

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AimTo date, the understanding and development of novel treatments for mental illness is hampered by inadequate animal models. For instance, it is unclear to what extent commonly used behavioural tests in animals can inform us on the mental and affective aspects of schizophrenia.MethodsTo link pathophysiological processes in an animal model to clinical findings, we have here utilized the recently developed Df(h15q13)/+ mouse model for detailed investigations of cortical neuronal engagement during pre‐attentive processing of auditory information from two back‐translational auditory paradigms. We also investigate if compromised putative fast‐spiking interneurone (FSI) function can be restored through pharmacological intervention using the Kv3.1 channel opener RE1. Chronic multi‐array electrodes in primary auditory cortex were used to record single cell firing from putative pyramidal and FSI in awake animals during processing of auditory sensory information.ResultsWe find a decreased amplitude in the response to auditory stimuli and reduced recruitment of neurones to fast steady‐state gamma oscillatory activity. These results resemble encephalography recordings in patients with schizophrenia. Furthermore, the probability of interneurones to fire with low interspike intervals during 80 Hz auditory stimulation was reduced in Df(h15q13)/+ mice, an effect that was partially reversed by the Kv3.1 channel modulator, RE1.ConclusionThis study offers insight into the consequences on a neuronal level of carrying the 15q13.3 microdeletion. Furthermore, it points to deficient functioning of interneurones as a potential pathophysiological mechanism in schizophrenia and suggests a therapeutic potential of Kv3.1 channel openers.

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“…found that ~90% of patients with schizophrenia as well as ~50% of their first-degree relatives exhibit insufficient inhibitory processing of repetitive, irrelevant acoustic stimuli (Bramon et al, 2004;De Wilde et al, 2007;Patterson et al, 2008). Typically assessed with the amplitude of the early (50 ms) positive ERP component, P50, abnormal auditory sensory gating has been evidenced by a relative inability to suppress P50 to S 2 , and is expressed by larger S 2 /S 1 ratio (rP50) and/or smaller S 1 minus S 2 difference (dP50) scores.…”

Section: Cihr Author Manuscriptmentioning

confidence: 99%

The moderating role of the dopamine transporter 1 gene on P50 sensory gating and its modulation by nicotine

et al. 2011

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Although schizophrenia has been considered primarily a disease of dopaminergic neurotransmission, the role of dopamine in auditory sensory gating deficits in this disorder and their amelioration by smoking/nicotine is unclear. Hypothesizing that individual differences in striatal dopamine levels may moderate auditory gating and its modulation by nicotine, this preliminary study used the mid-latency (P50) auditory event-related potential (ERP) to examine the single dose (6 mg) effects of nicotine (vs. placebo) gum on sensory gating in 24 healthy nonsmokers varying in the genetic expression of the dopamine transporter (DAT). Consistent with an inverted-U relationship between dopamine level and the drug effects, individuals carrying the 9R (lower gene expression) allele, which is related to greater striatal dopamine levels, tended to evidence increased baseline gating compared to 10R (higher gene expression) allele carriers and showed a reduction in gating with acute nicotine. The present results may help to understand the link between excessive smoking and sensory gating deficits in schizophrenia and to explain the potential functional implications of genetic disposition on nicotinic treatment in schizophrenia. Keywords schizophrenia; P50; gating; dopamine transporter gene; nicotine; smoking Early theoretical models of information processing in schizophrenia postulated impairment in the preattentive, automatic processing of sensory input to be a contributing factor in the appearance of psychotic symptoms, perceptual disturbances, and various cognitive deficits that characterize this disorder (Venables, 1964). Meta-analyses and reviews of event-related potential (ERP) studies probing auditory sensory gating in a paired stimulus paradigm (involving the presentation two [ CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscriptfound that ~90% of patients with schizophrenia as well as ~50% of their first-degree relatives exhibit insufficient inhibitory processing of repetitive, irrelevant acoustic stimuli (Bramon et al., 2004;De Wilde et al., 2007;Patterson et al., 2008). Typically assessed with the amplitude of the early (50 ms) positive ERP component, P50, abnormal auditory sensory gating has been evidenced by a relative inability to suppress P50 to S 2 , and is expressed by larger S 2 /S 1 ratio (rP50) and/or smaller S 1 minus S 2 difference (dP50) scores.Smoking and acute nicotine have transiently corrected deficient P50 processing in schizophrenia patients and their relatives, respectively (Adler et al., 1992(Adler et al., , 1993. In addition, in a rodent model of schizophrenia-like gating deficiency, studies assessing the P20-N40 ERP, which is an analogue of the human P50, have shown agonists and antagonists of the α7 nicotinic receptor to improve deficient S 2 inhibition and to block normal S 2 inhibition, respectively (Stevens et al., 1998(Stevens et al., , 1999Simosky et al., 2001). Other studies reporting gating improvements with nicotine in rodents and humans, however, have found increa...

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A meta-analysis of P50 studies in patients with schizophrenia and relatives: Differences in methodology between research groups

Cited by 144 publications

References 43 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

The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia

The moderating role of the dopamine transporter 1 gene on P50 sensory gating and its modulation by nicotine

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