Study Of Schizophrenia Patients Research Articles

SU6. Association of High Risk of Cardiovascular Disease With Increased Serum hsCRP Levels Progressively in Patients With Schizophrenia

Abstract Background: There is excess and premature mortality in schizophrenia (SZ), from both natural and unnatural causes, when compared to the general population. In a 15-year follow-up study of SZ patients, 22% had died, of which greater than 50% died from cardiovascular and respiratory diseases. Inflammation has been linked to all stages of atherosclerosis. Recent studies suggest a role of C-reactive protein (CRP) as a risk marker for cardiovascular disease (CVD). CRP is a blood-borne protein that is produced by hepatocytes and regulated by inflammatory cytokines. The purpose of this study was to test whether high risk of cardiovascular disease was associated with increased levels of serum high-sensitivity CRP (hsCRP) progressively during the course of schizophrenia development. Methods: Serum hsCRP contents were compared among first-episode antipsychotic-naive patients with SZ (FEAN-SZ, n = 24), early course SZ patients with duration of illness 20 years patients currently with (n = 21) and those without (n = 19) treatment with lipid lowering drugs (LLD). In addition, age- and gender-matched healthy control subjects (HC, n = 25) were used for baseline comparisons with FEAN-SZ group. The high risk of CVD in human subjects was determined according to the National Cholesterol Education Program Adult Treatment Panel III (ATP-III) guidelines. The hsCRP measures were categorized as low risk, 3 mg/l. Results: Similar to HC subjects, 79% FEAN-SZ patients had low-risk hsCRP values with only 8% and 13% in average- and high-risk values, respectively. However, as disease progressed, 33% of clinically stable ECSZ patients who were not identified at high risk of CVD had average- and high-risk values, respectively. Among CSZ patients without LLD, 79% had high risk and 21% had average risk of hsCRP values. Following LLD therapy, these values remained relative high with 62%, 29%, and 9% in high-, average-, and low-risk hsCRP values, respectively. In addition, levels of hsCRP were inversely correlated with levels of HDL cholesterol. Conclusion: Our present data support the notion that the addition of hsCRP to the ATP-III global risk score provides a more accurate assessment of CVD risk in SZ patients. Serum hsCRP may also be an early marker of CVD risk in schizophrenia. On the other hand, Lp(a) levels, considering as a “Heart Attack” cholesterol and a strongly inherited risk factor for CVD, were not elevated in either ECSZ or CSZ patients in the present study. (Supported in part by the American Heart Association and MH58141 grants.)

A Clinical Study Protocol to Identify Serum Biomarkers Predictive of Response to Antipsychotics in Schizophrenia Patients.

An increasing number of studies are now exploring the potential of using blood-based biomarkers for prediction of antipsychotic treatment response in studies of schizophrenia patients. Here we describe the detailed setup of a clinical study to identify biomarker candidates for prediction of response of patients prior to receiving antipsychotics over a 6-week treatment period. The main emphasis is on study design, patient recruitment, sampling and outcome measures.

Angry but not neutral faces facilitate response inhibition in schizophrenia patients.

Schizophrenia is a very heterogeneous disorder with extensive impairments in cognitive as well as emotional abilities. One critical domain is response inhibition, and previous studies in schizophrenia patients have mostly observed impairments, i.e., slower inhibition. Moreover, response inhibition to socially salient stimuli has not been investigated in schizophrenia so far. Therefore, to elucidate emotion-cognition interactions by examining potential emotional effects on inhibition processes and further investigate the association of cognition with inhibition we used an emotional stop signal task in 27 schizophrenia patients and 27 gender- and age-matched controls. Task irrelevant emotional faces (angry and neutral) were used as stimuli in a stop signal reaction time task. Regarding accuracy, patients showed significantly worse performance in neutral trials, while their performance in anger trials (stop and go) was similar to controls. Angry faces elicited faster response inhibition in both groups, underlining an emotional facilitation effect. Neurocognitive functions significantly correlated with accuracy in the stop signal task in schizophrenia patients, thus further strengthening the notion of the strong link between cognitive abilities and inhibition processes. Inhibitory control impairments are of high clinical interest due to their association with substance abuse, impulsive behavior and suicide. Based on our data, neutral faces significantly affect response inhibition in schizophrenia while an emotional facilitation effect was apparent for angry faces even in schizophrenia patients. Thus, our data further support the notion that neutral face processing is critically impaired in schizophrenia.

Predicting schizophrenia by fusing networks from SNPs, DNA methylation and fMRI data.

In order to comprehensively utilize complementary information from multiple types of data for better disease diagnosis, in this study, we applied a network fusion based approach to integrating three types of data including genetic, epigenetic and neuroimaging data from a study of schizophrenia patients (SCZ). A network is a map of interactions, which contributes to investigating the connectivity of components or links between sub-units. We exploited the potential of using networks as features for discriminating SCZ from healthy controls. We first constructed a single network from each type of data. Then we built four fused networks by the network fusion method: three fused networks for each combination of two types of data and one fused network for all three data types. Based on the local consistency of network, we can predict the group of the unlabeled SCZ subjects. The group prediction method was applied to test the power of network-based features and the performance was evaluated by a 10-fold cross validation. The results show that the prediction accuracy is the highest when applying our prediction method to the fused network derived from three data types among 7 tested networks. As a conclusion, integrative approaches that can comprehensively utilize multiple types of data are more useful for diagnosis and prediction.

Peptidomic analysis of the anterior temporal lobe and corpus callosum from schizophrenia patients

Schizophrenia is a complex disorder hypothesized to develop from a combination of genetic, neurodevelopmental, and environmental factors. Molecules that are directly involved in the pathogenesis of schizophrenia and may serve as biomarker candidates can be identified with “omics” approaches such as proteomics and peptidomics. In this context, we performed a peptidomic study in schizophrenia postmortem brains, to our knowledge the first such study in schizophrenia patients. We investigated the anterior temporal lobe (ATL) and corpus callosum (CC) by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and a label-free ion quantification technique based on data-dependent acquisition (DDA). Results indicated alterations in a specific intracellular neurogranin peptide in both the ATL and CC and a decrease of PepH, a fragment of histone H2B type 1-H intracellular peptide, in the ATL. PepH was tested in serum-deprived Neuro2A cells and showed a protective effect against cell death. Cells were also challenged with lipopolysaccharide (LPS), and PepH was able to prevent the endotoxic effects of LPS. Our data suggest that specific intracellular peptides are altered in schizophrenia patients. The potential biological activity of PepH supports intracellular peptides as novel targets in the study not only of schizophrenia but also of other neuropsychiatric diseases. Biological significancePsychiatric disorders are considerably more difficult to diagnose in their early stages. Usually, by the time the diagnosis is clear and clinical treatment can be started, the disorder is already established and thus of greater severity. Consequently, the scientific community has been searching for biomarker candidates that can aid the early detection of such disorders and for novel therapeutics to improve treatment or at least delay disease progression. Moreover, key molecules involved in the establishment of psychiatric diseases may help the understanding of their pathogenesis and thus drive the development of more effective treatments. The present work screened peptides that might be possible novel targets to control cell machinery in schizophrenia and identified an intracellular peptide with potential cytoprotective activity. To our knowledge, this is the first peptidomic study in schizophrenia patients.

Meta-Analysis of Functional Neuroimaging and Cognitive Control Studies in Schizophrenia: Preliminary Elucidation of a Core Dysfunctional Timing Network.

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimaging studies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimaging studies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile.

From “What” to “How”: The Effort to Fill the Gaps in Understanding Cognitive Processes Underpinning Remission in Schizophrenia

Introduction: The accumulation of robust evidence culminated in the establishment of the cognitive deficits as a core symptom of Schizophrenia (SCZ). To date, there has been reliable evidence that cognitive deficits are associated with poor symptomatic outcomes in SCZ. Nevertheless, they have not been incorporated in definitions of remission and a systematic understanding of how cognition contributes to remission is still lacking. Although the standardized remission in SCZ criteria proposed in 2005 has encouraged studies to understand the role of cognitive function in symptomatic remission from SCZ, most investigations were cross-sectional and have studied samples of chronically ill patients. The purpose of the present study was to bring together the efforts of recent follow-up studies in early in earlier stages of the disease to fill the gap in the literature on understanding how cognitive impairment is related to remission. Methods: A comprehensive search of the PsycINFO and MEDLINE/PUBMED databases was conducted. Results: One study evaluated executive functioning in Early-Onset Schizophrenia (EOS) across stages of illness and suggested that executive impairment is present at the onset of SCZ and persists in attenuated but stable form after the resolution of psychotic symptoms. Studies in first-episode schizophrenia (FES) patients highlighted that despite verbal memory performance is strongly related to clinical remission in FES spectrum, it appears to have not a meaningful contribution to functional recovery. Longitudinal studies in SCZ patients suggested that executive function and higher premorbid Intelligence Quotient (IQ) were the best predictors of remission. Conclusion: Since were emphasized the need to conduct longitudinal follow-up studies to assess the relation of cognitive performance to the proposed remission criteria, some efforts have been made to fill the gaps in understanding cognitive processes underpinning remission in schizophrenia. Notwithstanding the question regarding how aspects of symptomatic remission affect, and are affected by, aspects of cognitive function, remain not yet clarified, these long-term prospective studies addressing different domains of neurocognition in schizophrenia patients undergoing remission, mainly in early stages of illness, are being very enlightening to guide and encourage new researches.

Emotion recognition and theory of mind are related to gray matter volume of the prefrontal cortex in schizophrenia

Investigations of social cognition in schizophrenia have demonstrated consistent impairments compared to healthy controls. Functional imaging studies in schizophrenia patients and healthy controls have revealed that social cognitive processing depends critically on the amygdala and the prefrontal cortex (PFC). However, the relationship between social cognition and structural brain abnormalities in these regions in schizophrenia patients is less well understood. Measures of facial emotion recognition and theory of mind (ToM), two key social cognitive abilities, as well as face perception and IQ, were assessed in 166 patients with schizophrenia and 134 healthy controls. MRI brain scans were acquired. Automated parcellation of the brain to determine gray matter volume of the amygdala and the superior, middle, inferior and orbital PFC was performed. Between-group analyses showed poorer recognition of angry faces and ToM performance, and decreased amygdala and PFC gray matter volumes in schizophrenia patients as compared to healthy controls. Moreover, in schizophrenia patients, recognition of angry faces was associated with inferior PFC gray matter volume, particularly the pars triangularis (p=0.006), with poor performance being related to reduced pars triangularis gray matter volume. In addition, ToM ability was related to PFC gray matter volume, particularly middle PFC (p=0.001), in that poor ToM skills in schizophrenia patients were associated with reduced middle PFC gray matter volume. In conclusion, reduced PFC, but not amygdala, gray matter volume is associated with social cognitive deficits in schizophrenia.

Longitudinal in vivo maturational changes of metabolites in the prefrontal cortex of rats exposed to polyinosinic–polycytidylic acid in utero

Proton magnetic resonance spectroscopy (1H MRS) studies in schizophrenia patients generally report decreased levels of N-acetyl-aspartate (NAA), glutamate and glutathione, particularly in frontal cortex. However, these data are inconsistent in part due to confounds associated with clinical samples. The lack of validated diagnostic biomarkers also hampers analysis of the neurodevelopmental trajectory of neurochemical abnormalities. Rodent models are powerful tools to address these issues, particularly when combined with 1H MRS (clinically comparable technology). We investigated the trajectory of metabolic changes in the prefrontal cortex during brain maturation from adolescence to adulthood in vivo using 1H MRS in rats exposed prenatally to polyinosinic–polycytidylic acid (POL), a rodent model of maternal immune activation (MIA), an epidemiological risk factor for several psychiatric disorders with a neurodevelopmental origin. Longitudinal in vivo 1H MRS revealed a significant decrease in PFC levels of GSH and taurine in adult, but not adolescent rats. Significant age×MIA interactions for PFC levels of NAA were also observed. These data replicate some deficits observed in the PFC of patients with schizophrenia. There were no significant changes in the levels of glutamate or any other metabolite. These data suggest prenatal exposure to POL leads to subtle metabolic perturbations of the normal maturing PFC, which may be related to subsequent behavioural abnormalities. Further work is however required to examine any potential confound of shipping stress on the presumed imbalances in PFC metabolites in POL-exposed offspring. Testing the interactions between MIA with stress or genetic risk variants will also be an important advance.

Trajectories of subcortical volume change in schizophrenia: A 5-year follow-up

Longitudinal structural MRI studies in schizophrenia patients show a consistent pattern of excessive brain tissue loss over time, which appears in different stages of the disease. So far, little is known on how age (or illness duration) is related to subcortical volume change across the course of illness in schizophrenia patients as compared with healthy individuals.At baseline, 151 schizophrenia patients and 154 age and gender matched controls participated. Of these, 89 patients and 109 controls were rescanned after an interval of approximately five years. FreeSurfer was used for subcortical segmentations. Baseline volumes and volume changes were compared. Fits with different degrees of freedom were fitted to explain the effect of age on brain volume change per group. These fits were then compared between groups.At baseline, patients had significantly smaller volumes of the thalamus, and hippocampus and significantly larger volumes of the caudate, putamen, and globus pallidum as compared with controls. Over time, similar trajectories but with a significant difference in offset were found for caudate, amygdala, and thalamus (in males only), indicating that annual volume loss was more pronounced in patients. Curvilinear fits were found in controls for putamen and hippocampus, while linear fits were found for patients.Except for the accumbens and globus pallidum, subcortical volumes showed excessive loss over time in patients with schizophrenia. In the putamen and hippocampus, this loss may be explained by abnormal maturational processes during adulthood.

Brain structural imaging study in schizophrenia patients with violent aggressive behaviors

Objective To review recent neuroimaging studies of aggressive/violent behaviors in schizophrenia and related the neural circuits of aggressive behaviors, focusing on structure magnetic resonance imaging(MRI) method, published from 2000 to 2014. Methods A systematic literature search was conducted using articles from PsycINFO, Embase, Pubmed and Cnki published between 2000 and 2014, we usedaggressive,violent,schizophrenia,structure MRIas the key words, to explore the relationship between schizophrenia of aggressive/violent behaviors and the related neural circuits. Results Of the 18 studies included in the analysis, mostly were case-control studies, two were written in Chinese.The neuroimaging literature on aggression in schizophrenia revealed the related grey matter volume of brain areas which contained the frontal lobe, temporal lobe, amygdala, hippocampus, cerebelum and caudate nucleus. Conclusion Findings from the current reviews suggest that the occurrence of violent/aggressive behaviors of schizophrenia were related with serval neural circuits as the frontal-temporal cognitive circuit, Papez circuit, cerebellum advanced cognitive circuit and caudate nucleus-reward seeking circuits. However, the precise violent/aggressive neural mechanism has yet to be studied further. Key words: Violent/aggressive behavior; Schizophrenia; Structure magnetic resonance imaging

Estimation of nonlinear measures of schizophrenia patients' EEG in emotional states

The emotional dysfunction has been reported as a clinical symptom of the disorder in some studies of schizophrenia patients. To study the underlying brain dynamics during emotional states in schizophrenia patients by nonlinear analysis, the EEG signals can be investigated. The aim of this study was to estimate nonlinearity of schizophrenics' EEG, using the correlation dimension (D2) and the largest Lyapunov exponent (L1), at rest and while listening auditory stimuli with emotional content. EEG data were recorded under two conditions as resting-period and auditory stimulation periods (white noise (WN) and classical Turkish music (CTM)) during 8 min from schizophrenia patients and age-matched healthy controls. We found that the patients had significantly lower values of L1 at the left frontal, parietal and right central regions during whole procedure compared with controls and had a significantly higher D2 only in the F3 and the P4 regions during the CTM exposure. However, no significant L1 and D2 differences were found between periods for WN and CTM in schizophrenics. It can be concluded that schizophrenic brain has less flexible neural-networks in the left fronto-temporal area. The chaotic analysis may be a useful tool in analyzing the EEG to investigate the neurodynamics of the schizophrenia patients' brain during emotional stimuli.

Normal P50 Gating in Children with Autism, Yet Attenuated P50 Amplitude in the Asperger Subcategory.

Autism spectrum disorders (ASD) and schizophrenia are separate disorders, but there is evidence of conversion or comorbid overlap. The objective of this paper was to explore whether deficits in sensory gating, as seen in some schizophrenia patients, can also be found in a group of ASD children compared to neurotypically developed children. An additional aim was to investigate the possibility of subdividing our ASD sample based on these gating deficits. In a case-control design, we assessed gating of the P50 and N100 amplitude in 31 ASD children and 39 healthy matched controls (8-12 years) and screened for differences between groups and within the ASD group. We did not find disturbances in auditory P50 and N100 filtering in the group of ASD children as a whole, nor did we find abnormal P50 and N100 amplitudes. However, the P50 amplitude to the conditioning stimulus was significantly reduced in the Asperger subgroup compared to healthy controls. In contrast to what is usually reported for patients with schizophrenia, we found no evidence for sensory gating deficits in our group of ASD children taken as a whole. However, reduced P50 amplitude to conditioning stimuli was found in the Asperger group, which is similar to what has been described in some studies in schizophrenia patients. There was a positive correlation between the P50 amplitude of the conditioning stimuli and anxiety score in the pervasive developmental disorder not otherwise specified group, which indicates a relation between anxiety and sensory registration in this group.

A fundamental role for hippocampal parvalbumin in the dopamine hyperfunction associated with schizophrenia

Postmortem studies in schizophrenia patients have demonstrated robust alterations in GABAergic markers throughout the neuraxis. It has been suggested that these alterations are restricted to subpopulations of interneurons, such as those containing the calcium binding protein parvalbumin. Indeed, a reduction in parvalbumin expression is a consistent observation in human postmortem studies, as well as, in a wide and diverse variety of animal models. However, it still remains to be determined whether this decrease in parvalbumin expression contributes to, or is a consequence of the disease. Here we utilize lentiviral delivered shRNA and demonstrate that a selective reduction in parvalbumin mRNA expression induces hyperactivity within the ventral hippocampus. In addition, we observe downstream increases in dopamine neuron population activity without changes in average firing rate or percent burst firing. These changes in dopamine neuron activity were associated with an enhanced locomotor response to amphetamine administration. These data therefore demonstrate that a reduction in ventral hippocampal parvalbumin expression is sufficient, in and of itself, to induce an augmented dopamine system function and behavioral hyper-responsivity to amphetamine, implicating a potential key role for parvalbumin in the pathophysiology of schizophrenia.

Polyunsaturated fatty acids in emerging psychosis: a safer alternative?

A promising approach of indicated prevention in individuals at increased risk of psychosis was based on the finding of potential neuroprotective properties of omega-3 polyunsaturated fatty acids (PUFAs). Considering the rising interest in omega-3 PUFA supplementation as preventive treatment strategy in young people at risk of psychosis, the question of safety issues must be addressed. For this systematic review, a literature search for studies on omega-3 PUFAs for emerging psychosis with a focus on the safety profile was undertaken. Because limited data are available, information regarding potential side effects of omega-3 PUFAs was additionally derived from currently available data in psychotic disorders at different stages of the illness. Furthermore, helpful evidence from somatic disorders and healthy controls was used. In terms of safety issues, evidence from the randomized controlled trial in ultra-high-risk individuals and a variety of studies in schizophrenia patients strongly suggests that omega-3 PUFAs are safe and well tolerated even when used in relatively high doses. Most commonly occurring but clinically rarely significant are mild gastrointestinal symptoms; similarly, the slight risk of prolonged bleeding time has not been shown to be clinically relevant. Differential effects on metabolic parameters, most of which appear beneficial, have been reported. Taken together, one promising aspect of omega-3 PUFAs is that there seem to be no reports of relevant deleterious side effects in humans, even at high doses. The differential effects on lipid parameters and bleeding time are noteworthy and need further clarification.

Mediodorsal Thalamus Hypofunction Impairs Flexible Goal-Directed Behavior

BackgroundCognitive inflexibility is a core symptom of several mental disorders including schizophrenia. Brain imaging studies in schizophrenia patients performing cognitive tasks have reported decreased activation of the mediodorsal thalamus (MD). Using a pharmacogenetic approach to model MD hypofunction, we recently showed that decreasing MD activity impairs reversal learning in mice. While this demonstrates causality between MD hypofunction and cognitive inflexibility, questions remain about the elementary cognitive processes that account for the deficit. MethodsUsing the Designer Receptors Exclusively Activated by Designer Drugs system, we reversibly decreased MD activity during behavioral tasks assessing elementary cognitive processes inherent to flexible goal-directed behaviors, including extinction, contingency degradation, outcome devaluation, and Pavlovian-to-instrumental transfer (n = 134 mice). ResultsWhile MD hypofunction impaired reversal learning, it did not affect the ability to learn about nonrewarded cues or the ability to modulate action selection based on the outcome value. In contrast, decreasing MD activity delayed the ability to adapt to changes in the contingency between actions and their outcomes. In addition, while Pavlovian learning was not affected by MD hypofunction, decreasing MD activity during Pavlovian learning impaired the ability of conditioned stimuli to modulate instrumental behavior. ConclusionsMediodorsal thalamus hypofunction causes cognitive inflexibility reflected by an impaired ability to adapt actions when their consequences change. Furthermore, it alters the encoding of environmental stimuli so that they cannot be properly utilized to guide behavior. Modulating MD activity could be a potential therapeutic strategy for promoting adaptive behavior in human subjects with cognitive inflexibility.

EPA-1435 - Add-on clinical effects of simvastatin and ondansetron in patients with schizophrenia stabilized on antipsychotic treatment: Pilot study

Objectives There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but have been found to be anti-inflammatory and also decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that adjunctive Ondansetron is efficacious against schizophrenia symptoms. We carried out a feasibility study in schizophrenia patients (within 5 years of first diagnosis) to explore the adjunctive use of simvastatin and ondansetron on positive, negative and general psychopathology. Methods This was a 12 week rater blind placebo controlled study. All to gather 36 patients with DSM-IV diagnosis of schizophrenia were recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks using PANSS, CGI, GAF and AIMS. Results Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual (TAU) on PANSS total score, although, this was not statistically significant. In the secondary analyses, no significant differences were seen on CGI, GAF and AIMS. Conclusions Anti-inflammatory treatments have shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual. This study has led to a larger SMRI-funded, double blind, randomized control trial.

Add-on clinical effects of simvastatin and ondansetron in patients with schizophrenia stabilized on antipsychotic treatment: pilot study.

There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but have been found to be anti-inflammatory and also decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that adjunctive ondansetron is efficacious against schizophrenia symptoms. We carried out a feasibility study in schizophrenia patients (within 5 years of first diagnosis) to explore the adjunctive use of simvastatin and ondansetron on positive, negative and general psychopathology. This was a 12-week rater-blind placebo-controlled study. A total of 36 patients with DSM-IV diagnosis of schizophrenia were recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks using Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) scale, Global Assessment of Functioning (GAF) and Abnormal Involuntary Movement Scale (AIMS). Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared with treatment as usual (TAU) on PANSS total score, although this was not statistically significant. In the secondary analyses, no significant differences were seen on CGI, GAF and AIMS. Anti-inflammatory treatments have been shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared with TAU. This study has led to a larger Stanley Medical Research Institute (SMRI)-funded, double-blind, randomized control trial.

Classification of Schizophrenia Patients and Healthy Controls Using P100 Event-Related Potentials for Visual Processing

The study of event-related potentials (ERPs) is capable of elucidating the abnormalities in brain network dynamics relevant to the information-processing deficits in schizophrenia patients. In contrast to P50 and P300 ERPs, however, the results of P100 ERP studies in schizophrenia patients are less consistent. We have previously reported that P100 amplitudes did not differ significantly between patients with schizophrenia and healthy subjects. This result raised a question as to whether P100 ERPs carry information on brain network dynamics in schizophrenia patients that is distinct from normal controls. To answer this question, in this study we performed discrimination analysis on the P100 data. The rate of correct classification of patients and controls was high (80-90% depending on stimulus categories), indicating that patients have spatial patterns of P100 amplitudes that are distinguishable from those in healthy subjects. To further explore this possibility, we performed principal component analysis on the P100 data. For the patients, the first principal component represented global activity, the second component represented the reciprocal anterior-posterior activation, and the third component represented the hemispheric reciprocity in activity. The first and second components were similar to those of the control group; however, the third component in control subjects showed activation of the center versus anterior and posterior regions. This result is consistent with the notion of abnormalities in hemispheric asymmetries during the processing of sensory information in schizophrenia. In conclusion, this ERP study demonstrated that P100 amplitudes have information that can successfully classify patients and controls.

Cognitive remediation improves cognition and good cognitive performance increases time to relapse – results of a 5 year catamnestic study in schizophrenia patients

BackgroundCognitive deficits are stable features of schizophrenia that are linked to functional outcome. Cognitive remediation approaches have been proven successful in ameliorating these deficits, although effect sizes vary considerably. Whether cognitive deficits are serious predictors of clinical outcome is less clear.MethodsSixty patients suffering from schizophrenia were included in our sample, thirty of them received computer-assisted cognitive training, and thirty received occupational therapy. For a subsample of 55 patients, who could be traced over a period of five years after the end of the cognitive remediation intervention, time until first relapse and time in psychosis were determined retrospectively from their medical records.ResultsCognitive remediation significantly improved problem solving, memory and attention with high effect sizes. Employment status, a post test verbal memory performance measure and a measure of executive functioning outperformed all other measures in the prediction of time to relapse, while allocation to treatment group outperformed all other variables in the prediction of both cognitive measures.ConclusionsCognitive remediation of neurocognitive deficits thus makes sense in a twofold fashion: It enhances cognition directly and positively acts on clinical course indirectly via improved neurocognition.Trial registrationGerman Clinical Trials Register: DRKS00004880