A meta-analysis of P50 studies in patients with schizophrenia and relatives

Department of Psychiatry, Academic Medical Centre, University of Amsterdam, the Netherlands.
Schizophrenia Research (Impact Factor: 3.92). 01/2008; 97(1-3):137-51. DOI: 10.1016/j.schres.2007.04.028
Source: PubMed


To determine whether patients with schizophrenia as well as their relatives show deficits in sensory gating reflected by an abnormal P50 ratio and to quantify the differences from controls.
A systematic search on articles published between 1982 and 2006 was conducted. 28 patient studies that were suitable for analysis including 891 patients and 686 controls were retrieved. Six studies on P50 of relatives of schizophrenic patients were identified, including 317 relatives and 294 controls.
In the patient studies we found an P50 effect size of 1.28 (SD=0.72). We confirmed high variability in outcomes across studies. Almost half of the studies included where published by one laboratory of the University of Colorado and these results differed significantly from the results found in studies performed in other laboratories. We found correlations between effect size outcome and sound intensity, filter settings and subjects' position which could be explained by differences between the Colorado laboratory and the other groups. In the relative studies we found a mean P50 effect size of 0.85 (+/-0.42).
The differences in methodology and lack of reported demographics and methodology including raters blinding in some studies makes it hard to compare results across studies and to evaluate the validity and reliability of P50 as a candidate endophenotype for schizophrenia. There are large differences in outcomes from Colorado studies and non-Colorado studies. In contrast to the Colorado studies in the non-Colorado studies P50 suppression would not qualify as an endophenotype for schizophrenia. These differences might be explained by the differences in methodology e.g. lower levels of sound intensity, differences in filter settings and subjects' position. Finally we make some recommendations for future research based on the outcomes of this meta-analysis.

Download full-text


Available from: Lo J Bour, Oct 07, 2015
24 Reads
    • "Patients with schizophrenia often show a diminished response decrease from the 1st to the 2nd click (for review de Wilde et al., 2007; Patterson et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess whether the response decrement of auditory evoked potentials (AEPs) after stimulus repetition is affected by an interplay between sensitization and habituation. AEPs were recorded in 18 healthy participants. Stimulation consisted of trains with eight tones. The 6th stimulus of each train was a frequency deviant. The N100 amplitude to the 1st stimulus of the train was quantified in each trial. Trials with initially strong N100 responses and with initially weak N100 responses were averaged separately. For the total trial sample, the N100 and P200 amplitudes decreased from the 1st to the 2nd stimulus of the train but not thereafter. Trials with an initially strong N100 response were qualified by likewise larger N100 amplitudes to the 2nd stimulus, as compared to trials with initially weak N100 responses, and were characterized by a pronounced N100 amplitude decrease from standards to deviants. Our findings are difficult to reconcile with the view that the response decrement of AEP components after stimulus repetition is modulated by sensitization and habituation, as no evidence for either of these two processes could be obtained. The study provides further evidence against habituation as underlying mechanism for the AEP decrement after stimulus repetition. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 05/2015; DOI:10.1016/j.clinph.2015.04.071 · 3.10 Impact Factor
  • Source
    • "Generally, the utility of P50 paired-click measures has been limited by their unestablished reliability, unknown effects of time differences in peak selection methodology and rater blinding, poor signal-to-noise ratio, sound intensity, seating position and long protocol (de Wilde et al., 2007a, 2007b; Dalecki et al., 2011). In spite of controversies surrounding the P50 ERP, reduced P50 ratio in schizophrenia has been confirmed metaanalytically (Bramon et al., 2004; de Wilde et al., 2007a, 2007b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Individuals with an "Attenuated Psychosis Syndrome" (APS) have a 20-40% chance of developing a psychotic disorder within two years; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether P50 gating deficits could help to discriminate individuals with APS and also those who are particularly likely to make a transition to psychosis. Method: 36 cases meeting PACE (Personal Assessment and Crisis Evaluation) criteria for the APS, all free of antipsychotics, and 60 controls performed an auditory conditioning-testing experiment while their electroencephalogram was recorded. The P50 ratio and its C-T difference were compared between groups. Subjects received follow-up for up to 2 years to determine their clinical outcome. Results: The P50 ratio was significantly higher and C-T difference lower in the APS group compared to controls. Of the individuals with APS who completed the follow-up (n=36), nine (25%) developed psychosis. P50 ratio and the C-T difference did not significantly differ between those individuals who developed psychosis and those who did not within the APS group. Conclusion: P50 deficits appear to be associated with the pre-clinical phase of psychosis. However, due to the limitations of the study and its sample size, replication in an independent cohort is necessary, to clarify the role of P50 deficits in illness progression and whether this inexpensive and non-invasive EEG marker could be of clinical value in the prediction of psychosis outcomes amongst populations at risk.
    Schizophrenia Research 12/2014; 161(2-3). DOI:10.1016/j.schres.2014.12.021 · 3.92 Impact Factor
  • Source
    • "Patients have increased striatal presynaptic dopamine function (synthesis and release) (Fusar-Poli & Meyer-Lindenberg, 2013a), but no difference in presynaptic dopamine transporter density (Howes et al. 2012; Fusar-Poli & Meyer-Lindenberg, 2013a, b) Patients have poor information processing, language skills, verbal learning, prospective memory, working memory and theory of mind (Bokat & Goldberg, 2003; Dickinson et al. 2007; Bora et al. 2009a; Forbes et al. 2009; Wang et al. 2009; Bora & Pantelis, 2013) Medium effect sizes a Patients show increases in volume of the basal ganglia, lateral and third ventricles and increased frequency of large cavum septum pellucidum. They show reductions in whole brain volume, grey matter volume in the frontal lobe, superior temporal gyrus, medial temporal lobe, thalamus, insula, anterior cingulate, amygdala, inferior parietal gyrus and cerebellum, and reduced white matter in the mid-sagittal corpus callosum (Wright et al. 2000; Baiano et al. 2007; Arnone et al. 2008; Kempton et al. 2010; Adriano et al. 2010, 2012; Chan et al. 2011; Olabi et al. 2011; Trzesniak et al. 2011a, b; Shepherd et al. 2012; Fusar-Poli et al. 2013; Haijma et al. 2013) Patient show increased N400 peak latency and decreased N400 effect during semantic priming tasks, as well as more negative N400 amplitude during congruent stimuli, particularly tasks involving long stimulus onset asynchrony (>500 ms) (Wang et al. 2011) Patients have decreased levels of N-acetyl aspartate (Brugger et al. 2011; Kraguljac et al. 2012) First-degree relatives of patients show deficits in general intelligence, executive functioning, attention, language, visual and verbal memory, short-and long-term episodic memory, theory of mind, and smooth pursuit eye movement (Sitskoorn et al. 2004; Szoke et al. 2005; Whyte et al. 2005; Snitz et al. 2006; Trandafir et al. 2006; Calkins et al. 2008; Bora & Pantelis, 2013) People at high clinical risk for psychosis show deficits in theory of mind (Bora & Pantelis, 2013) Neurocognition and social cognition are related to functional outcomes (Fett et al. 2011; Schmidt et al. 2011; Irani et al. 2012) Patients report greater aversive emotion and arousal to neutral stimuli (Cohen & Minor, 2010; Llerena et al. 2012) Patients with a current substance use disorder have fewer negative symptoms than patients without a current substance use disorder (Potvin et al. 2006) Patients with former cannabis use perform better on cognitive tasks than patients without former cannabis use (Yucel et al. 2012) Small effect sizes a Cognitive deficits are greater in schizophrenia than bipolar disorder (Krabbendam et al. 2005; Bora et al. 2009b; Stefanopoulou et al. 2009) and are related to lower levels of insight (Aleman et al. 2006) Negative and disorganized symptoms are related to lower IQ, poor reasoning, attention, executive functioning, language skills, learning, speed of processing, visual and verbal memory and social cognition (Nieuwenstein et al. 2001; de Gracia Dominguez et al. 2009; Dibben et al. 2009; Ventura et al. 2010, 2013) Patients are more likely to be non-right handed (Sommer et al. 2001) There is increased severity of negative symptoms in patients with a family history of psychosis compared with patients without a family history (Esterberg et al. 2010), and significant concordance of disorganized and reality distortion symptoms between siblings with schizophrenia (Rietkerk et al. 2008) People at high clinical risk for psychosis show deficits in general intelligence, executive functioning, verbal and visual memory, verbal fluency, attention, working memory and social cognition (Fusar-Poli et al. 2012b) Moderate-quality evidence Large effect sizes a Patients have increased S100B protein levels in serum (Schroeter et al. 2009) Patients have increased markers for human endogenous retroviruses, Chlamydophilia pneumoniae, Chlamydophilia psittaci, Toxocara and Toxoplasma gondii (Arias et al. 2011; Torrey et al. 2012) Patients and their first-degree relatives show increased P50 ratio (not latency), indicating reduced sensory gating (Bramon et al. 2004; de Wilde et al. 2007), which may not be improved by antipsychotic medication (Su et al. 2012) Patients show reduced mismatch negativity, and the effect size increases with increasing duration of illness (Umbricht & Krljes, 2005) Patients have increased occurrence of minor physical anomalies of the head, eyes, mouth, ears, hands and feet (Weinberg et al. 2007; Xu et al. 2011) Patients show increased rigidity of thought, poor IQ, pre-morbid IQ, perceptual problem solving ability, attention, short-term and long-term memory, olfactory identification and acuity, executive functioning, social and emotion processing, slower motor and processing speed, smooth pursuit eye movement and self-recognition (Johnson-Selfridge & Zalewski, 2001; Schultz & Searleman, 2002; Pelletier et al. 2005; Dickinson et al. 2007; Sprong et al. 2007; O'Driscoll & Callahan, 2008; Bora et al. 2009a; Mesholam-Gately et al. 2009; Rajji et al. 2009; Chan et al. 2010a; Knowles et al. 2010; Kohler et al. 2010; Khandaker et al. 2011; Cohen et al. 2012; Savla et al. 2012; Waters et al. 2012) Antipsychotic-free patients have increased sleep latency and total sleep time, and decreased sleep efficiency and stage 2 sleep (Chouinard et al. 2004) Patients and their first-degree relatives show increased neurological soft signs, including dysfunction in motor coordination and sequencing, sensory integration and disinhibition compared with controls (Chan et al. 2010b, c) Patients with a cocaine use disorder show increased extrapyramidal symptoms (Potvin et al. 2009) Medium effect sizes a Patients have reduced blood BDNF concentrations, regardless of medication dosage or medication status (Green et al. 2011) Patients have increased markers for Borna disease virus (Arias et al. 2011) Patients show increases in immune system molecules IFN-γ, TGF-β, TNF-α and IL-6; acutely relapsed patients also show increases in IL-10, IL-IRA and IL-8; and first-episode (untreated) patients also show increases in sIL-2R, IL-1β and IL-12. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. True findings about schizophrenia remain elusive; many findings are not replicated and conflicting results are common. Well-conducted systematic reviews have the ability to make robust, generalizable conclusions, with good meta-analyses potentially providing the closest estimate of the true effect size. In this paper, we undertake a systematic approach to synthesising the available evidence from well-conducted systematic reviews on schizophrenia. Method. Reviews were identified by searching Medline, EMBASE, CINAHL, Current Contents and PsycINFO. The decision to include or exclude reviews, data extraction and quality assessments were conducted in duplicate. Evidence was graded as high quality if reviews contained large samples and robust results; and as moderate quality if reviews contained imprecision, inconsistency, smaller samples or study designs that may be prone to bias. Results. High- and moderate-quality evidence shows that numerous psychosocial and biomedical treatments are effective. Patients have relatively poor cognitive functioning, and subtle, but diverse, structural brain alterations, altered electrophysiological functioning and sleep patterns, minor physical anomalies, neurological soft signs, and sensory alterations. There are markers of infection, inflammation or altered immunological parameters; and there is increased mortality from a range of causes. Risk for schizophrenia is increased with cannabis use, pregnancy and birth complications, prenatal exposure to Toxoplasma gondii, childhood central nervous system viral infections, childhood adversities, urbanicity and immigration (first and second generation), particularly in certain ethnic groups. Developmental motor delays and lower intelligence quotient in childhood and adolescence are apparent. Conclusions. We conclude that while our knowledge of schizophrenia is very substantial, our understanding of it remains limited.
    Psychological Medicine 02/2014; 44(16). DOI:10.1017/S0033291714000166 · 5.94 Impact Factor
Show more