P50 gating at acute and post-acute phases of first-episode schizophrenia

ArticleinProgress in Neuro-Psychopharmacology and Biological Psychiatry 32(8):1952-6 · November 2008with4 Reads
Impact Factor: 3.69 · DOI: 10.1016/j.pnpbp.2008.09.018 · Source: PubMed

Deficit in P50 sensory gating has repeatedly been shown in schizophrenia. In order to determine the contribution of trait and/or state features to P50 gating deficit in schizophrenia we evaluated the P50 gating in patients with first-episode schizophrenia (FES) at acute and post-acute phases. Subject groups comprised 16 patients with FES and 24 healthy controls. Patients were tested at the acute phase of the illness and retested at the post-acute phase when their positive symptoms improved. During the testing at the acute phase five patients were neuroleptic-naive and the others were taking atypical antipsychotics which were started recently in order to control the acute excitation. Patients were receiving risperidone, olanzapine or quetiapine treatment at the post-acute phase. P50 gating was impaired in patients at the acute phase compared to controls. However, at the post-acute phase P50 gating was increased compared to the acute phase, reaching to the gating values of controls. P50 gating improvement might be emerged from atypical antipsychotic medication, although this can only be definitively determined by randomized studies including different antipsychotics.

    • "Like P50 wave suppression, prepulse inhibition of startle response is a measure of the capacity to suppress processing of or responding to a noise. Patients with schizophrenia display less ability to gate or suppress the response to the second stimulus in both measures (Adler et al., 1985; Braff et al., 1999 Braff et al., , 2001a Braff et al., , 2001b Brockhaus-Dumke et al., 2008; Chen et al., 2011; Devrim-Üçok et al., 2008; Freedman et al., 2000). This loss of gating function or pre-attentive buffering capacity is suggested to contribute to sensory overload, cognitive fragmentation and thought disorder in schizophrenia (Croft et al., 2001; Venables, 1960). "
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: The prevalence of tobacco use in the population with schizophrenia is enormously high. Moreover, nicotine dependence is found to be associated with symptom severity and poor outcome in patients with schizophrenia. The neurobiological mechanisms that explain schizophrenia-nicotine dependence comorbidity are not known. This study systematically reviews the evidence highlighting the contribution of nicotinic acetylcholine receptors (nAChRs) to nicotine abuse in schizophrenia. Methods: Electronic data bases (Medline, Google Scholar, and Web of Science) were searched using the selected key words that match the aims set forth for this review. A total of 276 articles were used for the qualitative synthesis of this review. Results: Substantial evidence from preclinical and clinical studies indicated that dysregulation of α7 and β2-subunit containing nAChRs account for the cognitive and affective symptoms of schizophrenia and nicotine use may represent a strategy to remediate these symptoms. Additionally, recent meta-analyses proposed that early tobacco use may itself increase the risk of developing schizophrenia. Genetic studies demonstrating that nAChR dysfunction that may act as a shared vulnerability factor for comorbid tobacco dependence and schizophrenia were found to support this view. The development of nAChR modulators was considered an effective therapeutic strategy to ameliorate psychiatric symptoms and to promote smoking cessation in schizophrenia patients. Conclusions: The relationship between schizophrenia and smoking is complex. While the debate for the self-medication versus addiction vulnerability hypothesis continues, it is widely accepted that a dysfunction in the central nAChRs represent a common substrate for various symptoms of schizophrenia and comorbid nicotine dependence.
    Full-text · Article · Jan 2016 · Schizophrenia Research
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    • "Patterson et al8 concluded that their meta-analysis confirms the existence of event-related potential deficits in schizophrenia, with significance similar to the most robust findings reported in neuroimaging and neuropsychology in schizophrenia. Similar conclusions found also several others meta-analytic or detailed review studies which show sensory gating impairments in early stages of schizophrenia that become more prominent in chronic stages of schizophrenia.8,11,13,15,114 Further meta-analytical data by Chang et al115 confirm that the sensory gating deficit in patients with schizophrenia is well documented; nevertheless, certain findings raise doubts about the validity and utility of the S2/S1 ratio as a measure of sensory gating. "
    [Show abstract] [Hide abstract] ABSTRACT: Sensory gating disturbances in schizophrenia are often described as an inability to filter redundant sensory stimuli that typically manifest as inability to gate neuronal responses related to the P50 wave, characterizing a decreased ability of the brain to inhibit various responses to insignificant stimuli. It implicates various deficits of perceptual and attentional functions, and this inability to inhibit, or "gate", irrelevant sensory inputs leads to sensory and information overload that also may result in neuronal hyperexcitability related to disturbances of habituation mechanisms. These findings seem to be particularly important in the context of modern electrophysiological and neuroimaging data suggesting that the filtering deficits in schizophrenia are likely related to deficits in the integrity of connections between various brain areas. As a consequence, this brain disintegration produces disconnection of information, disrupted binding, and disintegration of consciousness that in terms of modern neuroscience could connect original Bleuler's concept of "split mind" with research of neural information integration.
    Full-text · Article · Jul 2014 · Neuropsychiatric Disease and Treatment
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    • "The increase of P50 suppression in the low-gating group was because of reduction in S2-elicited amplitudes in the antipsychotic treatment conditions, suggesting that the ability to inhibit the response to the second stimulus was improved and gating was therefore increased. A similar increase of P50 gating was repeatedly shown in drug-naive first-episode and chronically ill schizophrenia patients after long-term treatment with AAPs (Devrim-Ucok et al, 2008; Light et al, 2000; Nagamoto et al, 1999; Oranje et al, 2013). However, Hong et al (2009) did not find a normalization of P50 suppression after 6 weeks of treatment with risperidone or clozapine in first-episode schizophrenia patients. "
    [Show abstract] [Hide abstract] ABSTRACT: Despite advances in treatment of schizophrenia spectrum disorders with atypical antipsychotics (AAPs), there is still need for compounds with improved efficacy/side-effect ratios. Evidence from challenge studies suggests that the assessment of gating functions in humans and rodents with naturally low gating levels might be a useful model to screen for novel compounds with antipsychotic properties. To further evaluate and extend this translational approach, three AAPs were examined. Compounds without antipsychotic properties served as negative control treatments. In a placebo-controlled within-subjects design, healthy males received either single doses of aripiprazole and risperidone (n=28), amisulpride and lorazepam (n=30), or modafinil and valproate (n=30), and placebo. Prepulse inhibiton (PPI) and P50-suppression were assessed. Clinically associated symptoms were evaluated using the SCL-90-R. Aripiprazole, risperidone, and amisulpride increased P50-suppression in low P50 gaters. Lorazepam, modafinil, and valproate did not influence P50-suppression in low gaters. Furthermore, low P50 gaters scored significantly higher on the SCL-90-R than high P50 gaters. Aripiprazole increased PPI in low PPI gaters while modafinil and lorazepam attenuated PPI in both groups. Risperidone, amisulpride, and valproate did not influence PPI. P50-suppression in low gaters appears to be an antipsychotic-sensitive neurophysiologic marker. This conclusion is supported by the association of low P50-suppression and higher clinically associated scores. Furthermore, PPI might be sensitive for atypical mechanisms of antipsychotic medication. The translational model investigating differential effects of AAPs on gating in healthy subjects with naturally low gating can be beneficial for phase I/II development-plans by providing additional information for critical decision-making.Neuropsychopharmacology accepted article preview online, 07 May 2014; doi:10.1038/npp.2014.102.
    Full-text · Article · May 2014 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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