Psychopathology Of Schizophrenia Research Articles

T16. SCHIZOPHRENIA SPECTRUM DISORDER: DEPRESSION TRAJECTORIES AND IMMUNE MARKERS

BackgroundGenetic findings imply a role of the immune system in the complex psychopathology of schizophrenia, and elevated serum levels of pro-inflammatory cytokines have been found in patients. Altered levels of cytokines are linked to severe depression and cognitive dysfunction, both of which are common among patients suffering from schizophrenia. Depression is important to diagnose in this patient population as consequences of untreated depression can be severe. In this study we will investigate if the level and change of immune markers in blood are related to depression in patients with schizophrenia spectrum disorders.MethodsThe study is part of the Bergen-Stavanger-Innsbruck-Trondheim study (BestIntro) which is a multicenter randomized controlled trial comparing treatment with amisulpride, aripirazole and olanzapine. The study included patients with schizophrenia spectrum disorders (ICD-10 F20-F29) above 18 years with a score of 4 or more one of the following items on the Positive and Negative Syndrome scale (PANSS): Delusions, hallucinations, grandiosity, suspiciousness/persecution and unusual thought content. Participants were followed throughout one year, and for this sub-study participants from all treatment arms were analyzed together. Blood samples were drawn at week 0, 1, 3, 6, 12, 26, 39 and 52. Depression was measured with the Calgary Depression Scale (CDSS) which distinguishes depression from negative symptoms. A panel of 9 immune markers were analyzed: interferon gamma (IFN-γ), interleukin 1-β (IL-1β), interleukin 10 (IL-10), interleukin 12p70 (IL-12p70), interleukin 17A (IL-17A), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). We examined whether the level and change in inflammation parameters could be predicted by latent classes describing CDSS trajectories.ResultsThe preliminary results suggest three different CDSS trajectories: high, moderate and low level of depression. In the three class model, the different groups were found to be related to some differences in level and change in the inflammation parameters. Baseline differences were found with higher IL-10 in the high depression group. In the 0–1 week interval, the low depression trajectory group reduced their IL1-beta, while the other two groups did not.DiscussionDifferent courses of change in depression were identified suggesting that trajectories exist. With regard to temporal patterns of inflammatory parameters, findings point in the opposite direction of the established links between pro-inflammatory cytokines and depression. Further studies should explore if cytokine alterations in schizophrenia per se can explain this difference, or if depression in schizophrenia differs in its underlying biology from regular depressive states.

M118. FACTOR STRUCTURE OF THE CLINICIAN-RATED DIMENSION OF PSYCHOSIS SYMPTOM SEVERITY IN PATIENTS WITH EARLY PSYCHOSIS

BackgroundThe early psychosis is classically viewed as a critical period. Schizophrenia subtypes which had been used to describe heterogeneity of the disease were discarded with the release of DSM-5 because of the lack of their clinical significance. DSM-5 has proposed the use of the Clinician-Rated Dimension of Psychosis Symptom Severity (CRDPSS) for evaluating the various symptoms of schizophrenia. The 8-domain CRDPSS was developed from the perspective of deconstructing the psychopathology of schizophrenia and would be expected to provide baseline data for further advances in psychiatric nosology. To our knowledge, despite these discussions, the dimensional structure of the CRDPSS has hardly been studied in the patients with early psychosis. The purpose of this study is to investigate the structure categorizing the items of dimensional assessment through factor analysis in patients with early psychosis.MethodsThe subjects were 497 patients with early psychosis who were enrolled in the Korean Early Psychosis Cohort Study. They were between ≥18 years and ≤45 years of age who fulfill the criteria of DSM-5 for schizophrenia spectrum and other psychotic disorders. In KEPS, early psychosis was defined the patients whose duration of treatment were within 2 years. The proportion of males was 41.9% and their mean age and age at onset were 28.7(SD=8.9) and 26.8(SD=9.1) years, respectively. An exploratory factor analysis(EFA) was conducted on the 8 items of dimensional assessment of psychosis in DSM-5 with principle components extracted by the varimax method.ResultsAn exploratory factor analysis(EFA) was conducted on the items of dimensional assessment of psychosis in DSM-5 with principle components extracted by the varimax method. Two factors were identified which were labeled as ‘psychotic’ and ‘deficit’ domain. The first factor included delusions (loading=0.834, communality=0.697), hallucinations(loading=0.800, communality=0.640), disorganization(loading=0.654, communality=0.642), and abnormal psychomotor behavior(loading=0.677, communality=0.549). The second factor included negative symptoms(loading=0.833, communality=0.703) and impaired cognition(loading=0.827, communality=0.697). Depression and mania were excluded in factor analysis due to statistical incompatibility such as lack of communality less than 0.4. Bartlett’s test for sphericity was significant (χ2 =817.996, p<0.001), and the total variance of the factor solution was 65.452%.DiscussionTwo factors were identified which were labeled as ‘psychotic’ and ‘deficit’ domain. The first factor included delusions, hallucinations, disorganization and abnormal psychomotor behavior. The second factor included negative symptoms and impaired cognition. To our knowledge, this study is the first attempt to analyze the early psychosis patients using the dimensional assessment of psychosis in DSM-5, and it would be meaningful to follow up the course with the cohort.

Interrelationships Between BDNF, Superoxide Dismutase, and Cognitive Impairment in Drug-Naive First-Episode Patients With Schizophrenia.

The pathogenesis and etiology of schizophrenia (SCZ) remains unclear. Accumulating studies showed that complex interrelationships between brain-derived neurotrophic factor (BDNF) and an imbalanced redox system has a crucial role in the psychopathology of SCZ. However, the influence of the interrelationships of BDNF and superoxide dismutase (SOD) on cognitive impairment and clinical symptomatology in drug-naive first-episode (DNFE) SCZ patients has not been studied thoroughly. Serum BDNF levels, plasma total SOD, manganese-SOD (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD) activities, and malondialdehyde (MDA) levels were measured in 327 DNFE patients with SCZ and 391 healthy controls. Cognitive functions were measured using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Compared with the controls, the DNFE patients had increased activities of total SOD and CuZn-SOD, and reduced levels of BDNF and MDA. BDNF levels were positively correlated with CuZn-SOD activity in patients. In addition, we found that elevated Mn-SOD and CuZn-SOD activities were related to PANSS depression factor. Moreover, an interactive effect of BDNF levels and Mn-SOD activity was associated with attentional index score in the patients. Therefore, our findings suggested that interrelationships between BDNF and antioxidant mechanisms might underlie the pathological mechanisms of cognitive impairments and symptomatology in the DNFE patients with SCZ.

An Analysis of Five TrkB Gene Polymorphisms in Schizophrenia and the Interaction of Its Haplotype with rs6265 BDNF Gene Polymorphism.

Aim The BDNF dysfunction in the schizophrenia has been soundly documented. The TrkB gene is a high-affinity receptor of the BDNF that is changed in schizophrenia and mood disorders. The study had two aims: first, to identify whether the five nucleotide polymorphisms (SNPs) in TrkB gene are associated with a diagnosis of schizophrenia; and the latter, if any association exists between the TrkB SNPs and psychopathology, suicide attempts, and family history of schizophrenia in a Caucasian population. Methods Case-control study (401 patients and 657 healthy controls) was used to examine a predisposition for schizophrenia. The tests for psychopathology, suicide attempts, and family history of schizophrenia were conducted only in patient group. The severity of the schizophrenia was measured using the five-factor model of the PANSS. In addition, the haplotype analysis for both the separate for SNPs of TrkB gene and in combination with the rs6265 SNP BDNF gene was conducted. Results Our case-control study revealed that the genetic variants of rs10868235 (T/T polymorphic genotype) and rs1387923 (G/G polymorphic genotype) of the TrkB gene were associated with a higher risk of developing schizophrenia in men. However, the A/A wild genotype of rs1387923 was connected with a lower risk for both the development of and the family manifestation of schizophrenia in men. The G polymorphic allele of rs1565445 was associated with an increased risk of suicide in schizophrenia. The tested SNPs of the TrkB gene did not modulate the psychopathology of schizophrenia. The haplotype that was built with five SNPs in the TrkB gene was protective for men, but after joining the rs6265 SNP of the BDNF gene, a haplotype that was protective for women was created.

Altered insulin-like growth factor-2 signaling is associated with psychopathology and cognitive deficits in patients with schizophrenia.

BackgroundSchizophrenia is linked with abnormal brain neurodevelopment, on which IGF-2 (insulin-like growth factor-2) has a great impact. The purpose of this study was to assess the levels of serum IGF-2 and its binding proteins IGFBP-3 and IGFBP-7 in schizophrenia patients and the associations of these proteins with schizophrenia psychopathology and cognitive deficits.MethodsThirty-two schizophrenia patients and 30 healthy controls were recruited. The PANSS and a neurocognitive test battery were used to assess schizophrenic symptomatology and cognition, respectively. Serum IGF-2, IGFBP-3 and IGFBP-7 levels were determined using ELISA.ResultsThe schizophrenia patients had a much lower content of serum IGF-2, IGFBP-3 and IGFBP-7 than controls. For the patients, IGF-2 levels were negatively correlated with the PANSS negative scores and positively associated with working memory, attention, and executive function. The correlations between IGF-2 and the PANSS negative scores, working memory or executive function were still significant after controlling for age, sex, education level, BMI, illness history and age of onset. No significant associations of IGFBP-3 or IGFBP-7 with the PANSS scores and cognitive function were observed in the patients.ConclusionsOur study demonstrates that serum IGF-2 was significantly correlated with negative and cognitive symptoms in patients with schizophrenia, suggesting that altered IGF-2 signaling may be implicated in the psychopathology and cognitive deficits in schizophrenia.

Glutamate and Dysconnection in the Salience Network: Neurochemical, Effective Connectivity, and Computational Evidence in Schizophrenia

BackgroundFunctional dysconnection in schizophrenia is underwritten by a pathophysiology of the glutamate neurotransmission that affects the excitation-inhibition balance in key nodes of the salience network. Physiologically, this manifests as aberrant effective connectivity in intrinsic connections involving inhibitory interneurons. In computational terms, this produces a pathology of evidence accumulation and ensuing inference in the brain. Finally, the pathophysiology and aberrant inference would partially account for the psychopathology of schizophrenia as measured in terms of symptoms and signs. We refer to this formulation as the 3-level hypothesis. MethodsWe tested the hypothesis in core nodes of the salience network (the dorsal anterior cingulate cortex [dACC] and the anterior insula) of 20 patients with first-episode psychosis and 20 healthy control subjects. We established 3-way correlations between the magnetic resonance spectroscopy measures of glutamate, effective connectivity of resting-state functional magnetic resonance imaging, and correlations between measures of this connectivity and estimates of precision (inherent in evidence accumulation in the Stroop task) and psychopathology. ResultsGlutamate concentration in the dACC was associated with higher and lower inhibitory connectivity in the dACC and in the anterior insula, respectively. Crucially, glutamate concentration correlated negatively with the inhibitory influence on the excitatory neuronal population in the dACC of subjects with first-episode psychosis. Furthermore, aberrant computational parameters of the Stroop task performance were associated with aberrant inhibitory connections. Finally, the strength of connections from the dACC to the anterior insula correlated negatively with severity of social withdrawal. ConclusionsThese findings support a link between glutamate-mediated cortical disinhibition, effective-connectivity deficits, and computational performance in psychosis.

Delay discounting abnormalities are seen in first-episode schizophrenia but not in bipolar disorder

Delay discounting (DD) is the phenomenon of individuals discounting future rewards as a function of time. It has been studied extensively in chronic schizophrenia (SZ) and the results of these studies have been variable. Comorbidity in chronic samples could be one reason for the mixed findings and studies in first-episode (FE) samples are surprisingly lacking. Bipolar disorder (BP) which shares some genetic and symptom features with SZ could serve as an interesting comparison group for DD but has been underexplored. Here we present the first study that combines FE SZ, FE BP with psychotic features, as well as healthy controls and study DD with two versions of the task. We found that SZ showed steeper discounting than HC and BP on the well-validated Kirby DD task. SZ showed no difference than HC on a separate DD task with smaller rewards presented with decimal places and shorter delays. As a preliminary finding, DD was found to be positively related to positive symptoms in FE SZ, while no relationship was found between negative symptoms and DD. In addition, we found comparable DD in BP compared to HC. Ultimately, our data may help elucidate the psychopathology in SZ and BP during intertemporal decision making.

P.063 Anti-dementia drugs for psychopathology and cognitive impairment in schizophrenia: a systematic review and meta-analysis

P.063 Anti-dementia drugs for psychopathology and cognitive impairment in schizophrenia: a systematic review and meta-analysis

P50 inhibition deficit in patients with chronic schizophrenia: Relationship with cognitive impairment of MATRICS consensus cognitive battery

ObjectiveCognitive impairment is a core symptom of schizophrenia (SCZ); however, its pathophysiological mechanisms remain unclear. The sensory gating (SG) deficits reflected by P50 inhibition are recurring in SCZ, and this inhibition may be related to the cognitive deficits seen in these individuals. This study aimed to investigate the relationship between P50 inhibition and cognitive dysfunction in SCZ, which has not been fully investigated up to this point. MethodsA total of 270 individuals with chronic SCZ and 116 healthy controls were enrolled in the study. Psychopathology of SCZ was rated by the positive and negative syndrome scale (PANSS), while cognitive function and P50 inhibition of subjects were assessed by the MATRICS Consensus Cognitive Battery (MCCB) and the electroencephalography system. ResultsThe MCCB total and its 10 index scores were significantly lower in patients than those in healthy controls (all p < 0.001). SCZ patients had a lower amplitude of S1, and higher P50 ratio than healthy controls (both p < 0.01). However, there were no significant correlations between the P50 ratio and any of the PANSS total and its subscale scores in SCZ patients (all p > 0.05). Moreover, no correlation was found between the P50 components and the MCCB scores (all p > 0.05). ConclusionsOur findings suggest that the P50 inhibition deficits occur in Chinese individuals with SCZ, which may not be associated with their clinical symptoms and cognitive impairment.

Social cognitive endophenotypes in schizophrenia: A study comparing first episode schizophrenia patients and, individuals at clinical- and familial- ‘at-risk’ for psychosis

Impairments in specific domains of social cognition have been suggested as possible endophenotypes for schizophrenia and clinical markers for accurate identification of ‘at-risk’ (AR) states. Aim of the present study was to find out whether performance on social cognition tasks will distinguish ‘clinical at-risk (CAR)’ and ‘familial at-risk (FAR)’ individuals from remitted first episode schizophrenia (FES) patients and healthy controls. Fifty in each of these four groups were included for analysis. Schizophrenia psychopathology in FES group was assessed using the Positive and Negative Syndrome Scale (PANSS). Theory of mind (ToM; first and second order (SOT and FOT), and faux pas composite (FPC)), attributional bias (AB) and social perception (SP) were assessed using the Social Cognition Rating Tool in Indian Setting (SOCRATIS). Facial emotion recognition task was used to assess emotional-expression recognition (ER). Significant differences in ToM, SP and ER between the four groups were found, even after controlling for performance on various neurocognitive tasks. ToM and SP were identified to follow an endophenotype pattern. While, both ToM and SP classified FES from healthy with large accuracy rates, SP, specifically, distinguished at-risk from disease groups. None of the social cognitive domains accurately classified familial at-risk from clinical at-risk groups. We conclude that social cognitive measures may be used as reliable endophenotype markers for schizophrenia and its sub-domains may be used for valid identification of AR individuals.

Effects of Prodromal Stage and Untreated Psychosis on Subsequent Psychopathology of Schizophrenia: A Path Analysis

Background: To examine psychopathology present under prolonged antipsychotic treatment in schizophrenia and to analyse their relationship to both the duration of the prodromal stage (DPS; time between onset of first unspecific psychological symptoms and first schizophrenic symptoms) and the duration of untreated psychosis (DUP; time between the onset of psychosis and the initiation of antipsychotic treatment). Methods: The psychopathology of 93 patients was assessed cross-sectionally using the Scales for the Assessment of Negative and Positive Symptoms and the Brief Psychiatric Rating Scale. DPS and DUP were assessed by means of the patient records and the Interview for the Retrospective Assessment of the Onset and Course of Schizophrenia and Other Psychoses. A path analysis using maximum likelihood estimation was conducted with the program Analysis of Moment Structures for Windows. Results: The resulting path model indicated that DPS was predictive for a more severe negative symptomatology in schizophrenia, whereas DUP was associated with a more severe positive symptomatology in the long-term. Furthermore, DUP showed an inverse correlation with the age of the patients at the onset of both first unspecific psychological symptoms and first schizophrenic symptoms. Conclusion: A long prodromal stage suggests an increased risk of a long-term progression with negative symptoms in schizophrenia, whereas a delayed start of antipsychotic treatment could lead to an increased manifestation and severity of positive symptoms in the long term. These results underline the need to shorten the duration of the prodrome by an early detection and adequate intervention in patients with increased risk to develop psychosis.

Targeted lipidomics and metabolomics evaluations of cortical neuronal stress in schizophrenia

BackgroundCortical neuronal dysfunction has been proposed to underlie the psychopathology and cognitive dysfunction of schizophrenia. Previously we have reported altered sphingolipid and N-acylphosphatidylserine (NAPS) metabolism in the frontal cortex in schizophrenia. We continue to expand these investigations to define the biochemical basis for these critical neuropathologies. MethodsWe undertook a targeted high resolution mass spectrometric analysis to validate our previous reports of elevated sphingolipids and NAPS in the frontal cortex of a new cohort of schizophrenia subjects. Furthermore we expanded these analyses to include ceramides, N-acylphosphatidylethanolamines (NAPE), and N-acylethanolamines (NAE). In the same tissue samples we examined N-acetylaspartylglutamate (NAAG), a modulator of excitatory amino acid transmission, hypothesized to be involved in the pathology of schizophrenia. ResultsWe repeated our observations of elevated sulfatides in the frontal cortex in schizophrenia. An in-depth analysis of other sphingolipids revealed decrements in ceramide levels and increased levels of lactosylceramides. NAPS also were found to be augmented in schizophrenia as we previously reported. In addition, levels of NAPES, established biomarkers of neuronal stress, were elevated while their metabolites, NAEs were decreased. With regard to excitatory amino acid neurotransmission, NAAG levels were decreased by 50% while the metabolic precursor, N-acetylaspartate was unaltered. ConclusionsOur data support the concept of cortical neuronal dysfunction in schizophrenia as indicated by altered metabolism of structural sphingolipids and NAAG, a modulator of excitatory amino acid neurotransmission.

Glucose disturbances, cognitive deficits and white matter abnormalities in first-episode drug-naive schizophrenia.

Disturbance of glucose metabolism may be implicated in cognitive deficits of schizophrenia in its early phases. Many studies have reported the important role of widespread disruption of white matter (WM) connectivity in pathogenesis, cognitive deficit and psychopathology of schizophrenia. However, no study has investigated their inter-relationships in drug-naive first episode(DNFE) patients with schizophrenia. Glucose metabolism parameters including fasting glucose, insulin and homeostasis model of assessment-insulin resistance (HOMA-IR) index, cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB) and the voxel-wised WM fractional anisotropy (FA) values were examined using DTI in 39 DNFE schizophrenia and 31 control subjects. The Positive and Negative Syndrome Scale was utilized for clinical symptoms. The patients showed significantly greater fasting plasma levels of glucose and insulin and HOMA-IR, and poorer cognitive scores, together with widespread reduced FA values in five brain areas, including left and right corpus callosum, superior longitudinal fasciculus, posterior thalamic radiation, and corona radiata (all p < 0.05). Association analysis showed that glucose level was positively associated with Digital Sequence Test and Continuous Performance Test, but negatively with FA values in posterior thalamic radiation and left corpus callosum in patients (all p < 0.05). Furthermore, multiple regression analysis revealed that the interactions of glucose × FA in left corpus callosum, longitudinal fasciculus and corona radiata were independent contributors to the Brief Visuospatial Memory Test (BVMT) of MCCB, while the interaction of glucose × FA in left corpus callosum, or in longitudinal fasciculus was associated with MCCB mazes and Trail Making A Test, respectively. Therefore, abnormal glucose metabolism, cognitive impairment and widespread disruption of WM structure occur in an early course of schizophrenia onset. An interaction between glucose metabolism abnormality and the WM dysconnectivity may lead to cognitive impairment.

Psychosis as an adverse effect of monoclonal antibody immunotherapy

Immunotherapy is a “hot” area in schizophrenia research. Monoclonal antibodies (mAbs) target specific immune molecules, and therefore offer an unparalleled opportunity to directly test the hypothesis that immune dysfunction plays a causal role in psychopathology in schizophrenia. Cytokine-based immunotherapy for other disorders has been associated with a range of neuropsychiatric adverse effects, including psychosis. The purpose of the present study was to investigate the prevalence of spontaneously-reported adverse drug reactions of psychotic symptoms for mAbs, and to calculate odds of psychosis for individual mAbs, compared to bevacizumab, which does not directly target the immune system. We searched the publicly available VigiBase, a World Health Organization global individual case safety report database from inception through February 2019 for which a mAb was the suspected agent of an adverse drug reaction (ADR). We investigated 43 different mAbs, comprising 1,298,185 case reports and 2025 psychosis ADRs. For individual mAbs, the prevalence of psychosis ADRs ranged from 0.1 to 0.4%. Seven mAbs were associated with a significantly increased odds of psychosis (OR = 1.42–2.22), including two agents that target CD25. Eight mAbs were associated with a significantly decreased odds of psychosis (OR = 0.28–0.75), including 4 anti-TNF-α agents. Our results suggest that psychosis is a relatively rare adverse effect of mAb treatment, but risks vary by specific agents. Findings indicate that modulating the immune system may sometimes lead to the development of psychosis. Ongoing clinical trials of adjunctive mAb immunotherapy in schizophrenia will provide valuable insights into the role of the immune system in psychosis.

Schizophrenia and Corollary Discharge: A Neuroscientific Overview and Translational Implications.

Corollary discharge mechanism refers to the suppression of sensory consequences of self-generated actions; a process that serves to distinguish between self and non-self based on discrimination of origination of action. It explains, say for example, why we cannot tickle ourselves. This review discusses how corollary discharge model is an essential neural integration mechanism central to the motor functioning of animal kingdom. In this article, research conducted in the field of corollary discharge has been reviewed to understand the neuroanatomical and neurophysiological basis of corollary discharge and gain insight into the biochemical basis of its dysfunction. This review article also explores the role of corollary discharge and its dysfunction in the presentation of symptoms of schizophrenia, discussing the findings from corollary discharge studies on schizophrenia population. Lastly, the link between schizophrenia psychopathology and corollary discharge dysfunction has been highlighted, and an attempt has been made to establish a case for correction of corollary discharge deficit in schizophrenia through neuromodulation.

F12. CHANGES IN BRAIN INFLAMMATION ARE RELATED TO SYMPTOMS AND AEROBIC EXERCISE IN FIRST EPISODE SCHIZOPHRENIA

Research continues to show that persistent brain inflammation may be one mechanism through which genetic, biological, or environmental risk factors might impact the etiology and psychopathology of schizophrenia. Elevated levels of pro-inflammatory and lower levels of anti-inflammatory cytokines have been reported in meta-analyses of multi-episode schizophrenia patients when compared to controls. Similar findings have been described in meta-analysis in first episode schizophrenia patients for cytokines such as IL1β, sIL2r, IL-6, and TNF-α. Certain cytokines might be key participants in the regulation of neuro-inflammation in schizophrenia. Specifically, IL-6, a pro-inflammatory cytokine, may act as a primary regulator. In fact, IL-6 in multi-episode patients has been associated inversely with symptoms. Yet, little is known about the role these cytokines play in first episode schizophrenia patients and how best to reduce their impact. Outpatients in the early course of schizophrenia who were being treated in the UCLA Aftercare Program were assessed at baseline and at a 6-month follow-up point. Patients were within 2 years of their first psychotic episode, were an average of 22.6 years old and had an average of 13.1 years of education. Patients were participants in a RCT of Cognitive Training alone vs Cognitive Training & Exercise. For 25 patients, we assayed blood collected at baseline and 6 months for IL-6. To assess symptoms, we administered the BPRS at baseline and every two weeks up to the 6-month study end point. We examined the relationship between changes in the pro-inflammatory cytokine IL-6 and the change in depression from baseline to the 6-month follow-up point. We found increases in levels of IL-6 were significantly related to increases in BPRS depressive symptoms (n=25, r=.40, p=.04). In examining the RCT effects, the group by time effect was not statistically significant. However, within the Cognitive Training & Exercise group, the number of aerobic exercise sessions completed was significantly correlated with the amount of reduction in brain inflammation as measured by IL-6 (n=13, r=-.63, p=.02). This is the first study to examine in first episode schizophrenia patients the longitudinal relationship between cytokines and symptoms over time and the effects of aerobic exercise on cytokines. The study findings indicate that an increase in a pro-inflammatory cytokine is associated with an increase in depressive symptoms during six months of treatment. Associations between cytokine level and depression suggest that inflammation might have deleterious effects on the early course of these symptoms. The reductions observed in IL-6 with aerobic exercise suggests that exercise may be a promising intervention to reduce the deleterious effects of brain inflammation.

Cortico-thalamic dysconnection in early-stage schizophrenia: a functional connectivity magnetic resonance imaging study.

Studies have indicated thalamus-related network dysfunction in schizophrenia and psychotic disorders. However, whether thalamus-related functional connectivity (FC) contributes to the psychopathology and cognitive deficits of early-stage schizophrenia requires further investigation. A total of 34 patients with early-stage schizophrenia (illness duration = 1.62 ± 1.16 years; age = 26.00 ± 6.34years) and 34 age- and sex-matched healthy controls were enrolled in our study and underwent comprehensive assessments of the clinical symptoms of schizophrenia, working memory tasks, and resting-state FC magnetic resonance imaging. The patients with early-stage schizophrenia had increased FC of the thalamus with the bilateral postcentral and temporal gyri, inferior occipital cortex, and temporal pole and decreased FC of the thalamus with the vestibulocerebellum and frontal pole compared with the controls. Furthermore, increased FC between the thalamus and temporal pole was positively correlated with positive scores of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and negatively correlated with performance on working memory tasks in early-stage schizophrenia. Increased FC of the thalamus with the inferior occipital cortex was positively associated with negative PANSS scores and negatively correlated with Personal and Social Performance Scale scores in early-stage schizophrenia. Our results supported the vital role of thalamus-related network dysfunction in the psychopathology and cognitive deficits of early-stage schizophrenia.

Association between decreased serum TBIL concentration and immediate memory impairment in schizophrenia patients

Cognitive impairment is a core feature of schizophrenia (SCH). In addition to the toxic effect of Bilirubin (BIL), it has antioxidant properties that were associated with the psychopathology and cognitive impairment of psychiatric disorders. The aim of this study was to examine the correlation of serum total BIL (TBIL) concentration with cognitive impairment in SCH patients. We recruited 34 SCH patients and 119 healthy controls (HCs) in this case-control design. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Serum TBIL concentration was measured using the immunoturbidimetric method. Serum TBIL concentration was significantly decreased in SCH patients compared to HCs after adjusting for age, gender, and education. Serum TBIL concentration in SCH patients was also positively correlated with the RBANS immediate memory score. Further stepwise multiple regression analysis confirmed the positive association between serum TBIL concentration and immediate memory score in SCH patients. Our findings supported that the decline in serum TBIL concentration was associated with the immediate memory impairment and psychopathology of SCH.

What We Know and Still Need to Know about Gender Aspects of Delusional Disorder: A Narrative Review of Recent Work

While gender differences in the psychopathology and clinical course of schizophrenia have been extensively reported, the potential for analogous differences in delusional disorder has been understudied. Our aim in this paper is to focus on the recent literature on delusional disorder and to explore gender aspects. This is a non-systematic, narrative and critical review. The review is divided into the following main sections: gender differences in epidemiology, symptomatology, phenotypic factor analyses, psychiatric comorbidity, response and adherence to medications, and clinical trajectories. Culture-bound delusional syndromes are also addressed, and potential causes for gender differences and their treatment are critically discussed. Although DMS-5 reports no gender differences in the frequency of delusional disorder or in delusional content, several studies have found erotomania to be more frequent in women. There seem also to be gender differences in affective and substance abuse comorbidity, which may prove clinically important. The loss of the neuroprotection conferred by estrogens during the reproductive period in women may trigger depressive symptoms after menopause. The interaction of age and gender has been insufficiently studied as is also the case for selective cultural pressures on men and women and their impact on the content of delusions. Studies designed to focus on gender differences in response to treatment are currently needed in delusional disorder

Increased brain-derived neurotrophic factor exon IV histone 3 lysine 9 dimethylation in patients with schizophrenia

Background: Studies have mentioned that mixed-lineage leukemia 1 (MLL1) and histone 3 lysine 4 trimethylation (H3K4me3) of brain-derived neurotrophic factor (BDNF) exon IV from the postmortem brain tissue of patients with schizophrenia are related to the psychopathology of schizophrenia. We intended to investigate the levels of MLL1 messenger RNA (mRNA) and BDNF exon IV histone H3K9me2 and K27me3 in peripheral blood of patients with schizophrenia and healthy controls and to evaluate the relationships between aforementioned biomarkers and patients with/without clozapine treatment. Methods: During a one-year period, we recruited 36 patients with schizophrenia and 32 healthy controls. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS). We sampled 10 mL of peripheral blood from each participant to analyze the MLL1 mRNA and BDNF exon IV H3K9me2 and K27me3 levels. Results: Significantly higher blood H3K9me2 (p