Abstract
BackgroundPeople with schizophrenia and related psychotic disorders show abnormalities in several organ systems in addition to the central nervous system (CNS). It is not yet known how the magnitude of disturbance in non-CNS systems compares with the magnitude of CNS disturbance in FEP. Here, we statistically compare effect sizes (ES) for non-CNS and CNS dysfunction in FEP, and consider whether schizophrenia is a multi-system disorder.MethodsPubmed was systematically searched from 1990 to May 2017 for meta-analyses examining non-CNS dysfunction in FEP, focusing on immune, cardiometabolic, and hypothalamic-pituitary-adrenal (HPA) systems. A parallel search was performed for meta-analyses examining representative CNS dysfunction in FEP, specifically neurophysiological, neurochemical and brain structural alterations. To statistically compare the magnitude of effect sizes (ES) between different CNS and non-CNS systems in FEP, data were extracted from case-control studies making up these meta-analyses, and meta-analyses repeated. For non-CNS parameters, random-effects meta-analyses were performed examining immune (cytokines, CRP, and lymphocytes), cardiometabolic (glucose/insulin and lipids), and HPA parameters (cortisol and prolactin). For CNS parameters, meta-analyses were performed examining brain structural, neurophysiological (Auditory P300 amplitude and latency, duration deviant mismatch negativity), and neurochemical parameters (N-acetylaspartic acid levels). Standardized mean differences between patient and control cohort parameters were used as the ES (Hedges adjusted g). As well as individual meta-analyses being run for each parameter as described, 6 separate sub-group meta-analyses were performed examining data for overall immune, cardiometabolic, HPA, brain structural, neurophysiological, and neurochemical systems. Sub-group summary effect size magnitudes were calculated by running a combined analysis of all studies assigned to a sub-group (e.g. to calculate the summary effect size magnitude for immune alterations, a single analysis was performed that combined IL-1b, sIL-2R, IL-6, TNFa, TGFb, CRP, and lymphocyte count data sets). Summary effect sizes for these 6 individual systems were statistically compared in a fixed effects model using a Wald-type test. This was also used to compare overall summary CNS and non-CNS effect sizes. Antipsychotic naïve sensitivity analyses were performed.ResultsData were extracted for 165 studies comprising a total sample size of 13,440. The summary effect size for immune alterations (g=1.19; CI:0.82–1.56) was significantly greater than brain structural (g=0.40;P<.001) and neurochemical alterations (g=0.43;P<.001), and no different from neurophysiological alterations (g=0.80; P=0.05). The summary effect size for HPA alterations (g=0.68; CI:0.32–1.04) was not significantly different from brain structural (P=.14), neurophysiological (P=.54), and neurochemical (P=.22) alterations. The summary effect size for cardiometabolic alterations (g=0.23; CI:0.15–0.31) was significantly lower than neurochemical (P=.04), neurophysiological (P<.001) and brain structural alterations (P=.001). The overall summary effect sizes for non-CNS (g=0.58; CI:0.44–0.72) and CNS (g=0.50; CI:0.44–0.56) alterations were not significantly different (P=.28).DiscussionThese data indicate that there are robust alterations in non-CNS systems in psychosis, and that these are broadly similar in magnitude to a range of CNS alterations, indicating that psychosis involves multiple organ systems to a comparable degree from onset. We consider three models that could account for these findings and discuss implications for future research and treatment.
Highlights
Offspring of patients with schizophrenia and bipolar disorder are at increased risk to develop psychopathology
In the ACC, NR after 1.5 months showed a trend for lower GABA/Cr at baseline (p=0.06), and in NR after 6 months baseline GABA/Cr was significantly lower compared with healthy controls (HC) (p=0.03), whereas R and HC did not differ
intracranial volume (ICV) was not explained by psychopathology, even though there was no significant difference in ‘any psychopathology’ between SZo and BDo
Summary
Neuropsychological deficiencies in attentional processes and filtering of information are shown by both patients with schizophrenia and Attention Deficit Hyperactivity Disorder (ADHD). Given that behavioral symptoms differ, differential neurophysiological processes are likely to be underlying each disorder. Deficiencies in early auditory processing measured by event-related potentials (ERPs) such as the P300 amplitude and mismatch negativity are suggested to be biomarkers for schizophrenia. We study if these electrophysiological processes are impaired in,
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