Psychopathology Of Schizophrenia Research Articles

Exploring the link between inflammation and mental disorders

Mental disorders constitute 13% of the global disease burden. Schizophrenia, major depressive disorders (MDD) and bipolar disorders are among the most disabling disorders. Some of the inflammatory markers such as homocysteine, tumor necrosis alpha (TNF), C-reactive protein (CRP), and interleukin (IL)-6 have a contribution to influence mental disorder. The serum concentration of C-reactive protein (CRP) wasusedas a nonspecific index of systemic inflammation. Elevated levels of CRP as evidence for an inflammatory etiology of schizophrenia, and as indicators of more severe clinical symptoms and psychopathology of schizophrenia. The inflammatory marker also increases in the depressed patient. Proinflammatory cytokines might inhibit hippocampal neurogenesis which could lead to a reduced hippocampal volume, which is in depression. Anxiety symptoms were correlated to increase cytokine levels. Elevated inflammation in particular found in both men and women with the onset of anxiety disorder later in life.

N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N-acetylcysteine (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar disorder, and schizophrenia. The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed. Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = -0.74, 95% CI: -1.43, -0.06; I2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders. Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.

Suicide attempt, clinical correlates, and BDNF Val66Met polymorphism in chronic patients with schizophrenia.

Recent evidence suggests the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidal behavior. Because schizophrenia patients usually have high suicide rates and numerous studies have suggested that BDNF may contribute to the psychopathology of schizophrenia, we hypothesized that the functional polymorphism of BDNF (Val66Met) was associated with suicide attempts in patients with schizophrenia in a Chinese Han population. This polymorphism was genotyped in 825 chronic schizophrenia patients with (n = 123) and without (n = 702) suicide attempts and 445 healthy controls without a history of suicide attempts using a case-control design. The schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale. There were no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls. However, we found the Val allele (p = .023) and the Val/Val genotypes (p = .058) to be associated with a history of suicide attempts. Moreover, some clinical characteristics, including age and cigarettes smoked each day, interacted with the BDNF gene variant and appeared to play an important role in suicide attempts among schizophrenia patients. The BDNF Val66Met polymorphism itself and its interaction with some clinical variables may influence suicide attempts among schizophrenia patients. (PsycINFO Database Record

Nicotine dependence in Croatian male inpatients with schizophrenia

BackgroundPatients with schizophrenia have the highest known rates of cigarette smoking, but less is known about their smoking behavior and the differences across geographical regions, including Croatia.The aim of this study was to compare patterns of nicotine dependence between patients with schizophrenia and healthy individuals, and to determine the relationship between clinical presentation and the severity of smoking.MethodsThis cross-sectional study included 182 recently hospitalized male inpatients and 280 healthy males, who were daily smokers. All participants have fulfilled the Fagerstrom Test for Nicotine Dependence (FTND). Patients were also evaluated by the Positive and Negative Syndrome Scale (PANSS).ResultsPatients had higher FTND total score (p = 0.010), smoked their first cigarette earlier in the morning (p = 0.000), consumed higher number of cigarettes (p = 0.000), while healthy subjects had more difficulties to refrain from smoking in places where it is forbidden (p = 0.000) and smoked more even when they were sick (p = 0.000). While severe dependence was more prevalent in the patient group, light dependence was more frequent in control subjects (p = 0.04). Smoking behavior was not associated with either PANSS total score or any of its subscales and items.ConclusionsSmokers with schizophrenia differ from healthy smokers in both smoking behavior and level of dependence. Longitudinal studies are needed to shed more light on the complex relationship between smoking and psychopathology in schizophrenia.

Study of the Effect of Memantine on Negative Sign in Patients with Schizophrenia and Schizoaffective Disorders.

Memantine, an uncompetitive antagonist of glutamate receptor of the N-methyl-D-aspartate type is approved for the treatment of moderate to severe Alzheimer disease (1). A growing body of evidence supports a link between the glutamatergic neurotransmission and schizophrenia (2). The aim of this study was to examine the efficacy and safety of memantine as an adjunctive treatment for antipsychotics in patient with psychopathology of schizophrenia and schizoaffective. In this study, we assessed the effect of memantine on the pro-inflammatory cytokines such as IL6, TNFα and CRP. In this double-blind, placebo-controlled study, participants were assigned to receive (5-20 mg/day) memantine (n = 29) or placebo (n = 29), in addition to continuing treatment with antipsychotic for 12 weeks. The primary efficacy measure was the level of pro-inflammatory cytokines (TNFA, IL6, CRP). Safety was assessed by means of physical examination, clinical laboratory evaluation, recording of adverse event (AEs), and measure of extrapyramidal symptoms. At end point, comparison of biomarkers (IL6, TNFα and CRP) in two groups before and after treatment showed a significant decrease of TNFα (P < 0.001), but the difference was not significant in CRP and IL6 level (p = 0.92 and p = 0.77, respectively). The frequency of serious AEs in the memantine vs. placebo group was similar.

Different shades of default mode disturbance in schizophrenia: Subnodal covariance estimation in structure and function.

Schizophrenia is a devastating mental disease with an apparent disruption in the highly associative default mode network (DMN). Interplay between this canonical network and others probably contributes to goal-directed behavior so its disturbance is a candidate neural fingerprint underlying schizophrenia psychopathology. Previous research has reported both hyperconnectivity and hypoconnectivity within the DMN, and both increased and decreased DMN coupling with the multimodal saliency network (SN) and dorsal attention network (DAN). This study systematically revisited network disruption in patients with schizophrenia using data-derived network atlases and multivariate pattern-learning algorithms in a multisite dataset (n = 325). Resting-state fluctuations in unconstrained brain states were used to estimate functional connectivity, and local volume differences between individuals were used to estimate structural co-occurrence within and between the DMN, SN, and DAN. In brain structure and function, sparse inverse covariance estimates of network coupling were used to characterize healthy participants and patients with schizophrenia, and to identify statistically significant group differences. Evidence did not confirm that the backbone of the DMN was the primary driver of brain dysfunction in schizophrenia. Instead, functional and structural aberrations were frequently located outside of the DMN core, such as in the anterior temporoparietal junction and precuneus. Additionally, functional covariation analyses highlighted dysfunctional DMN-DAN coupling, while structural covariation results highlighted aberrant DMN-SN coupling. Our findings reframe the role of the DMN core and its relation to canonical networks in schizophrenia. We thus underline the importance of large-scale neural interactions as effective biomarkers and indicators of how to tailor psychiatric care to single patients.

In male rats, the ability of central insulin to suppress glucose production is impaired by olanzapine, whereas glucose uptake is left intact

Insulin receptors are widely expressed in the brain and may represent a crossroad between metabolic and cognitive disorders. Although antipsychotics, such as olanzapine, are the cornerstone treatment for schizophrenia, they are associated with high rates of type 2 diabetes and lack efficacy for illness-related cognitive deficits. Historically, this risk of diabetes was attributed to the weight gain propensity of antipsychotics, but recent work suggests antipsychotics can have weight-independent diabetogenic effects involving unknown brain-mediated mechanisms. Here, we examined whether antipsychotics disrupt central insulin action, hypothesizing that olanzapine would impair the well-established ability of central insulin to supress hepatic glucose production. Pancreatic euglycemic clamps were used to measure glucose kinetics alongside a central infusion of insulin or vehicle into the third ventricle. Male rats were pretreated with olanzapine or vehicle per our established model of acute olanzapine-induced peripheral insulin resistance. Groups included (central-peripheral) vehicle-vehicle (n = 11), insulin-vehicle (n = 10), insulin-olanzapine (n = 10) and vehicle-olanzapine (n = 8). There were no differences in peripheral glucose or insulin levels. Unexpectedly, we showed that central insulin increased glucose uptake, and this effect was not perturbed by olanzapine. We replicated suppression of glucose production by insulin (clamp relative to basal: 77.9% ± 13.1%, all p < 0.05), an effect abolished by olanzapine (insulin-olanzapine: 7.7% ± 14%). This study used only male rats and an acute dose of olanzapine. To our knowledge, this is the first study suggesting olanzapine may impair central insulin sensing, elucidating a potential mechanism of antipsychotic-induced diabetes and opening avenues of investigation related to domains of schizophrenia psychopathology.

P.3.f.021 - Genetic variants within key nodes of the cascade of antipsychotic mechanisms: effects on treatment response and schizophrenia psychopathology

P.3.f.021 - Genetic variants within key nodes of the cascade of antipsychotic mechanisms: effects on treatment response and schizophrenia psychopathology

Childhood trauma, depression, and sleep quality and their association with psychotic symptoms and suicidality in schizophrenia

This study involved the examination of the relationship between childhood trauma and both psychotic symptoms and suicidality in patients with schizophrenia after controlling for the possible confounding factors, such as clinical features, depression, and sleep quality. The Childhood Trauma Questionnaire-Short Form, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Pittsburgh Sleep Quality Index (PSQI), and the suicidality subscale of Mini-International Neuropsychiatric Interview (MINI) were administered to 199 patients with schizophrenia. We used sequential multiple stepwise regression analyses in which positive symptoms, negative symptoms, overall psychopathology, total symptoms of schizophrenia, and suicidality were dependent variables.Depressive symptomatology and childhood physical abuse significantly contributed to positive, negative, general psychopathology, and global schizophrenia symptomatology. Interestingly, general psychopathology scores were negatively associated with childhood physical neglect. Also, subjective sleep quality significantly contributed to positive schizophrenia symptoms. Although prior suicide attempts and depression were significant antecedents of suicidal ideation, no association between suicidality and both childhood trauma and sleep was found. Childhood physical abuse could have an impact on psychopathology in schizophrenia. In addition to childhood trauma, depression, sleep disturbances, and clinical features should be considered and inquired about in the course of clinical care of schizophrenia patients.

Schizophrenia symptomatic associations with diffusion tensor imaging measured fractional anisotropy of brain: a meta-analysis.

Several studies have examined the relationships between diffusion tensor imaging (DTI)-measured fractional anisotropy (FA) and the symptoms of schizophrenia, but results vary across the studies. The aim of this study was to carry out a meta-analysis of correlation coefficients reported by relevant studies to evaluate the correlative relationships between FA of various parts of the brain and schizophrenia symptomatic assessments. Literature was searched in several electronic databases, and study selection was based on précised eligibility criteria. Correlation coefficients between FA of a part of the brain and schizophrenia symptom were first converted into Fisher's z-scores for meta-analyses, and then overall effect sizes were back transformed to correlation coefficients. Thirty-three studies (1121 schizophrenia patients; age 32.66years [95% confidence interval (CI) 30.19, 35.13]; 65.95% [57.63, 74.28] males) were included in this meta-analysis. Age was inversely associated with brain FA (z-scores [95% CI] -0.23 [-0.14, -0.32]; p˂0.00001). Brain FA of various areas was inversely associated with negative symptoms of schizophrenia (z-score -0.30 [-0.23, -0.36]; p˂0.00001) but was positively associated with positive symptoms of schizophrenia (z-score 0.16 [0.04, 0.27]; p=0.007) and general psychopathology of schizophrenia (z-score 0.26 [0.15, 0.37]; p=0.00001). Although, DTI-measured brain FA is found to be inversely associated with negative symptoms and positively associated with positive symptoms and general psychopathology of schizophrenia, the effect sizes of these correlations are low and may not be clinically significant. Moreover, brain FA was also negatively associated with age of patients.

Whole brain volume changes and its correlation with clinical symptom severity in patients with schizophrenia: A DARTEL-based VBM study.

The purpose of this study was to evaluate gray matter (GM) and white matter (WM) volume alterations in whole-brain structures in patients with schizophrenia and healthy controls using voxel-based morphometry (VBM), and further to assess the correlation between GM and WM volume variations and symptom severity in schizophrenia. A total of 22 patients with schizophrenia and 22 age-matched healthy controls participated. Magnetic resonance image data were processed using SPM8 software with diffeomorphic anatomical registration via an exponentiated Lie algebra (DARTEL) algorithm. Patients with schizophrenia exhibited significantly decreased GM volumes of the insula, superior temporal gyrus (STG), gyrus rectus, and anterior cingulate cortex (ACC) compared with healthy controls. The GM volumes of the STG and gyrus rectus were negatively correlated with the positive scales on the Positive and Negative Syndrome Scale (PANSS) and those of the STG and ACC were negatively correlated with the negative scales. The durations of illness in schizophrenia were negatively correlated with the GM volumes of the insula, STG, and ACC. Patients with schizophrenia exhibited significantly decreased WM volumes of the superior frontal gyrus, inferior temporal gyrus, and STG. The WM volumes of the STG were negatively correlated with the duration of illness. Our findings suggest that GM and WM volume abnormalities in the STG are associated with the psychopathology of schizophrenia.

Genetic Variants Within Key Nodes of the Cascade of Antipsychotic Mechanisms: Effects on Antipsychotic Response and Schizophrenia Psychopathology in a Naturalistic Treatment Setting in Two Independent Korean and Italian Samples.

Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. Genetic factors play an important role in both SCZ liability and its treatment outcome. In the present paper, we investigated the effects of several single nucleotide polymorphisms (SNPs) within ten strong candidate genes involved with antipsychotics (APs) mechanisms of action. Two independent samples were investigated in the present study. Totals of 176 SCZ subjects and 326 controls of Korean ancestry, and 83 SCZ subjects and 194 controls of Italian ancestry were recruited and genotyped. SCZ risk and other parameters were also investigated. Concerning APs response, only a nominal association with HOMER1 rs3822568 in the Korean sample was found. In the haplotype analysis, rs9801117 C-rs12668837 C-rs4621754 A haplotype within ESYT2 and NCAPG2 genes was associated with APs response in the same sample. As for secondary outcomes, rs7439 within PKDCC and rs12668837 within NCAPG2 were associated with SCZ risk in the Italian sample. In the haplotype analysis, rs2788478 G-rs2657375 T-rs1039621 A within the region between WDR60 and ESYT genes and rs2013 C (ESYT2)-rs6459896 A (NCAPG2) haplotypes were associated with SCZ in the same sample. No association was found in the Korean sample. Finally, our exploratory data suggest a possible modulation of HOMER1, ARC, BDNF, TXNRD2, WDR60, and ESYT2 genes in the APs response to specific symptom clusters. Our results did not support a primary role for the genes investigated in the APs response. On the other hand, our secondary results suggest a possible involvement of NACPG2 and PKDCC in SCZ liability. Finally, our exploratory findings may deserve further investigations in specific studies.

Diversity or disarray? A systematic review of decision-making capacity for treatment and research in schizophrenia and other non-affective psychoses.

Valid consent for treatment or research participation requires that an individual has decision-making capacity (DMC), which is the ability to make a specific decision. There is evidence that the psychopathology of schizophrenia can compromise DMC. The objective of this review was to examine the presence or absence of DMC in schizophrenia and the socio-demographic/psychopathological factors associated. We searched three databases Embase, Ovid MEDLINE(R), and PsycINFO for studies reporting data on the proportion of DMC for treatment and research (DMC-T and DMC-R), and/or socio-demographic/psychopathological associations with ability to make such decisions, in people with schizophrenia and related illnesses. A total of 40 studies were identified. While high levels of heterogeneity limited direct comparison, meta-analysis of inpatient data showed that DMC-T was present in 48% of people. Insight was strongly associated with DMC-T. Neurocognitive deficits were strongly associated with lack of DMC-R and to a lesser extent DMC-T. With the exception of years of education, there was no evidence for an association with socio-demographic factors. Insight and neurocognitive deficits are most closely associated with DMC in schizophrenia. The lack of an association with socio-demographic factors dispels common misperceptions regarding DMC and characteristics such as age. Although our results reveal a wide spectrum of DMC-T and DMC-R in schizophrenia, this could be partly due to the complexity of the DMC construct and the heterogeneity of existing studies. To facilitate systematic review research, there is a need for improvement within research study design and increased consistency of concepts and tools.

Visual and motor functions in schizophrenia

IntroductionOver the past decade, perceptual organization has gained an increasingly important role in the psychopathology of schizophrenia. With the advancements in visual neurocognitive sciences, visual processing, especially mid- and high-level processing have been linked with psychotic symptoms, as well as prodromal and ultra-high risk patients. Motor dysfunction is being seen as well as an integral element of schizophrenia, separate from the other symptoms and with possible implications for disease risk and outcome. This could illustrate two systems at work, which by either individual dysfunction or integrative disorganization help explain some the neurocognitive mechanisms in schizophrenia.Objective and aimsThe current study's argument is that tests from these two domains could be used in a complementary manner to offer a neurocognitive characterization of schizophrenic patients.MethodsA total of 24 patients and 19 controls were evaluated. In order to assess mid-level visual perception the Leuven Perceptual Organization Screening Test was used, along with a scale for assessing soft neurological signs and a task for gait and motor imagery. Clinical symptoms were measured with the Positive And Negative Symptoms Scale, using the five-factor model as proposed by Lindenmayer. Data analysis involved comparison of means between patient and control groups as well as a multivariate factor analysis calculating the impact of perceptual and motor functions on clinical symptoms.ResultsConsistent with previous findings, visual and motor functions would differentiate between patient and control groups. In accordance with the study's aim, visual and motor functions had different impact on symptom dimensions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Memory and medial temporal lobe structures in patients with schizophrenia and their siblings

Episodic retrieval is characterized by the subjective experience of remembering. Semantic memory, on the other hand, is a more structured record of facts, meanings, concepts and knowledge about the external world that we have acquired. The medial temporal lobe (MTL), especially the hippocampus and parahippocampal cortex, plays a central role in both types of memory process. Published studies suggested that individuals with schizophrenia have deficits in episodic and semantic memory, as well as structural abnormalities of the medial temporal lobe. However, it is not clear whether reported correlations reflect the impact of the disease state or that of underlying genetic influences contributing to the risk. To understand better etiology and effects of psychosis on the global brain structure and cognitive processing, relatives of individuals with schizophrenia can be studied. The aim of our study was to examine the association between abnormalities of the MTL, psychopathology, and memory impairment in schizophrenia. Study sample (n = 60) consisted of first episode schizophrenia patients, their non-psychotic siblings and matching control subjects. We used high-resolution magnetic resonance imaging and probabilistic algorithms for image analysis. Episodic and semantic memory was measured with neuropsychological tests. Our results showed differences in memory performance between the groups. Neuropsychological data were correlated with MRI findings. The results may provide insight into etiology of schizophrenia and its effects on cognition and help to identify neuroanatomical and cognitive endophenotypes of psychotic disorders.Supported by the grant projects MH CR AZV 15-28998A, MEYS NPU4NUDZ: LO1611; Czech Science Foundation, grant No. 16-13093S; Institutional Support 00023001IKEM.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Relationship between childhood trauma and psychotic symptoms in patients with schizophrenia

IntroductionThe association between childhood trauma and psychotic symptoms is still not clearly understood. Findings for positive and negative symptoms are confounding. This symptomatic response may differ according to the type of childhood trauma, for example childhood abuse was associated with positive symptoms while childhood neglect was associated with negative symptoms.ObjectivesThis study examined the relationship between childhood trauma and psychotic symptoms in schizophrenic patients after controlling for the possible confounding factors, such as clinical features, depression, and sleep quality.MethodsThe childhood trauma questionnaire – short form, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia, Pittsburgh sleep quality index, and the suicidality subscale of mini-international neuropsychiatric interview were administered to 199 patients with schizophrenia. We used sequential multiple stepwise regression analyses in which positive symptoms, negative symptoms, overall psychopathology and total symptoms of schizophrenia were dependent variables.ResultsDepressive symptomatology and childhood physical abuse (CPA) significantly contributed to positive, negative, general psychopathology and global schizophrenia symptomatology. Stepwise regression analysis results are presented in Table 1.ConclusionsOur findings suggest that CPA during childhood could have an impact on psychopathology in schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Relationships between smoking, psychopathology and medication outside effects in schizophrenia

AimTo determine the relationship between smoking status and clinical characteristics of schizophrenic patients.MethodsIt was a cross-sectional study. One hundred and seventy-five schizophrenic outpatients were assessed by the Positive And Negative Syndrome Scale (PANSS), the Global Assessment of Functioning Scale (GAF), the scale of measurement of abnormal involuntary movements (AIMS) and by the rating scale akathisia caused by a drug Thomas Barnes. Current smokers (n = 85) were compared to non-smokers (n = 90) on clinical variables.ResultsThe mean number of cigarettes was 15 cig/day. In our sample, current smokers account for half of the patients and were exclusively men. Smokers were significantly more single patients (76.5 vs. 58.9, P = 0.01). There were no significant differences between smokers and non-smokers regarding clinical variables, including age of onset of the disease, the duration of the disease, the severity of positive and negative symptoms, and GAF scores. Smoking was significantly associated with more frequent prescription of conventional neuroleptics (98.8 vs. 92%, P = 0.03) and poorer adherence to treatment (77 vs. 62.2%, P = 0.02). There were no significant differences between the 2 groups regarding the average doses of neuroleptics, the presence of extrapyramidal signs, scores on the AIMS score and akathisia.ConclusionSmoking is common in patients suffering from schizophrenia. Smoking status should be considered in the assessment of neuroleptic treatment in schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Side effects of clozapine and their relationship with clinical variables in patients with schizophrenia

IntroductionThe side effects of clozapine may affect the treatment process negatively, and increase the disability.AimsWe aimed to assess the side effects of clozapine, and their relationship with the clinical variables in schizophrenia patients, and study the predictors of disability.MethodsConsecutive 122 outpatients who met DSM-IV criteria for schizophrenia, and were on clozapine treatment were included in the study. Information about sociodemographic characteristics, past and current clinical status were gathered through a clinical interview and review of the medical records, and physical measures and laboratory tests, including clozapine plasma levels, were recorded. The patients were assessed with SCID-I, Positive and Negative Syndrome Scale, UKU-Side Effect Rating Scale, WHO-Disability Assessment Schedule-II.ResultsHypersalivation, weight gain, sedation and constipation were the most common side effects of clozapine. Although the mean plasma clozapine levels were high (828.11 ± 445.5 ng/mL), no significant effect of clozapine dose and plasma levels were detected on the severity of side effects, except for constipation. Metabolic syndrome prevalence was found to be 50% according to ATP IIIA criteria. Duration of clozapine treatment, clozapine dose and plasma levels were not significantly different between patients with and without metabolic syndrome. Regression analysis showed that the severity of schizophrenia psychopathology and the number of side effects predicted the severity of disability.ConclusionsSide effects of clozapine increase the disability of patients with schizophrenia and should be monitored regularly. On the other hand, clozapine dose and plasma levels do not determine the severity of most of the common side effects.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The Evolution of negative symptom constructs

IntroductionNegative symptoms represent a separate dimension of schizophrenia psychopathology, distinct from positive symptoms, disorganization and cognitive impairment. It is increasingly acknowledged that negative symptoms are associated with poor functional outcome and represent an unmet need in schizophrenia treatment. Improvement in definition of their phenomenology, assessment instruments and experimental models are needed in order to improve schizophrenia prognosis.AimsThe presentation will review key aspects of the evolution of negative symptom constructs. In particular, findings concerning phenomenology, clinical assessment, association with functional outcome and brain imaging correlates will be presented.MethodsWe searched PubMed for English full-text publications with the keywordsSchizophrenia AND “negative symptoms”/“primary negative symptoms”/“deficit schizophrenia”/“persistent negative symptoms”/“affective flattening”/alogia/“expressive deficit”/apathy/asociality/“social withdrawal”/anhedonia/“anticipatory anhedonia”/avolition/neuroimaging.ResultsThe distinction between secondary negative symptoms (i.e., those due to identifiable factors, such as drug effects, psychotic symptoms or depression), and primary or persistent negative symptoms (i.e., those etiologically related to the core pathophysiology of schizophrenia) is grounded on solid research evidence and might have major implications for both treatment development and clinical care. The evidence that negative symptoms cluster in motivation- and expressive-related domains is founded on large consensus and empirical evidence and will foster pathophysiological modeling. The motivation-related domain is a stronger predictor of functional outcome than the expressive one.ConclusionsAn improved definition and assessment of negative symptoms needs to translate in large-scale studies to advance knowledge. In the short-term, the improved identification of treatable causes of secondary negative symptoms can translate into better care for people with schizophrenia.Disclosure of interestAM received honoraria or advisory board/consulting fees from the following companies: Janssen Pharmaceuticals, Otsuka, Pfizer and Pierre Fabre.SG received honoraria or advisory board/consulting fees from the following companies: Lundbeck, Janssen Pharmaceuticals, Hoffman-La Roche, Angelini-Acraf, Otsuka, Pierre Fabre and Gedeon-Richter.

Increased serum levels of cysteine in patients with schizophrenia: A potential marker of cognitive function preservation

BackgroundOxidative stress has been implicated in the psychopathology of schizophrenia. Cysteine, a semi-essential amino acid, is the precursor of the antioxidant glutathione. The aim of this study was to investigate the differences in serum levels of cysteine between patients with schizophrenia and healthy controls. The relationships between levels of cysteine, psychopathology and cognitive function were also explored. MethodsWe recruited 65 patients with schizophrenia and 65 age- and gender-matched healthy controls. Blood samples were collected to determine the serum levels of cysteine and plasma levels of metabolic parameters. The cognitive function of participants was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). The psychopathology of schizophrenic patients was evaluated using the Positive and Negative Syndrome Scale. ResultsSerum cysteine levels were significantly higher in schizophrenic patients than in controls (P<0.001). In patients with schizophrenia, serum levels of cysteine were positively correlated with cognitive function in terms of verbal memory (P=0.013), working memory (P=0.004), verbal fluency (P=0.027), attention and processing speed (P=0.025), executive function (P=0.024) and the composite score on the BACS (P=0.013). In healthy controls, no significant correlation was observed between cysteine level and cognitive function. ConclusionsThese findings suggest that oxidative stress may be involved in the pathogenesis of schizophrenia, and compensatory elevated levels of cysteine may serve as an indicator of cognition preservation. Further prospective studies are warranted to investigate the dynamic alterations in cysteine and the underlying pathophysiology of schizophrenia.