Symptoms In Chronic Schizophrenia Research Articles

A Review on Biological Mechanisms of Negative Symptoms in Chronic Schizophrenia

Research about the negative symptoms of chronic schizophrenia (SZ) is still lagging behind, in order to more comprehensively and systematically understand the biological and molecular mechanisms behind them, as well as to explore more valuable research directions and treatment options. By summarizing the results of previous studies and exploring them at the levels of neurobiology, genetics, molecular biology and microbiology, the authors provide a preliminary review of the new research progress in recent years. The authors hypothesize neurodevelopmental disorders by thoroughly investigating the anatomical features of various brain regions and the corresponding abnormalities in neurotransmitters. This paper then provides a relatively fresh perspective by summarizing the potential pathogenic mechanisms in terms of the brain-gut axis and metabolic syndrome. Ultimately, it is determined that the pathophysiology of chronic schizophrenia is associated with multiple biological mechanisms within the body, primarily arising from neurological abnormalities within the brain. On the basis of this, the author provides a conceptualization of the pathophysiology and a potential course of treatment.

Retraction: Abdallah MS, Mosalam EM, Hassan A, etal. Pentoxifylline as an adjunctive in treatment of negative symptoms in chronic schizophrenia: A double-blind, randomized, placebo-controlled trial. CNS Neurosci. Ther. 2023;29:354-364 (https://doi.org/10.1111/cns.14010).

Retraction: Abdallah MS, Mosalam EM, Hassan A, etal. Pentoxifylline as an adjunctive in treatment of negative symptoms in chronic schizophrenia: A double-blind, randomized, placebo-controlled trial. CNS Neurosci. Ther. 2023;29:354-364 (https://doi.org/10.1111/cns.14010) The above article, published online on November 07, 2022 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the journal's Editor-in-Chief, Xiaoming Hu, and John Wiley and Sons Ltd. Following publication, the Editor-in-Chief raised concerns about the integrity of the clinical trial. An investigation revealed significant issues regarding the reliability of the reported data. As a result, the Editor-in-Chief no longer has confidence in the validity of the results presented in this article.

Retraction: Abdallah MS, Mosalam EM, Hassan A, etal. Pentoxifylline as an adjunctive in treatment of negative symptoms in chronic schizophrenia: A double-blind, randomized, placebo-controlled trial. CNS Neurosci. Ther. 2023;29:354-364 (https://doi.org/10.1111/cns.14010).

Retraction: Abdallah MS, Ramadan AN, Omara-Reda H, etal. Double-blind, randomized, placebo-controlled pilot study of the phosphodiesterase-3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder. CNS Neurosci. Ther. 2021;27:1540-1548 (https://doi.org/10.1111/cns.13731) The above article, published online on September 21, 2021 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the journal's Editor-in-Chief, Xiaoming Hu, and John Wiley and Sons Ltd. Following publication, multiple concerns were raised by a third party about the integrity of the clinical trial. An investigation revealed significant issues regarding the reliability of the reported data. As a result, the Editor-in-Chief no longer has confidence in the validity of the results presented in this article.

High-definition transcranial direct current stimulation for treating cognitive and negative symptoms in chronic schizophrenia – A sham-controlled proof of concept study

Objectives: Cognitive and negative symptoms are core symptoms of schizophrenia affecting interpersonal and socio-occupational functioning. Impaired dorsolateral prefrontal cortex (DLPFC) function is implicated in negative and cognitive symptoms. Conventional transcranial direct current stimulation (tDCS) to DLPFC has attracted interest as an add-on treatment for these symptoms. High-definition tDCS (HD-tDCS), an optimized form of tDCS, has the potential for more focalized neuromodulation. Studies suggest that an increased number of sessions may increase the effectiveness of stimulation. Hence, we aimed to evaluate the efficacy of 20 sessions of HD-tDCS over the left DLPFC in the improvement of cognitive and negative symptoms in chronic schizophrenia (>2 years continuous illness). Material and Methods: Twenty patients with chronic schizophrenia with predominantly cognitive and negative symptoms were enrolled in this sham-controlled trial. Participants received 20 sessions of HD-tDCS at 2 mA for 20 min, that is, twice daily over 10 days. Montreal cognitive assessment and scale for assessment of negative symptoms were used to assess outcome variables. Assessments were carried out at baseline, 2 weeks, and 6 weeks, respectively. Results: Significant improvement was noted in both active and sham groups across all outcome variables over time. However, a statistically significant decrease in negative symptoms in the active group was noted, which was maintained at the end of 6 weeks, but there was no statistically significant improvement in cognitive symptoms between the active and sham groups at 6 weeks. The stimulation protocol was well tolerated. Conclusion: HD-tDCS has substantial potential in the treatment of negative symptoms; however, its role in cognitive symptoms needs further evaluation.

Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs

QuestionThis umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.Study selection and analysisFollowing the Preferred Reporting Items for Systematic Reviews...

Interaction between high interleukin-2 and high cortisol levels is associated with psychopathology in patients with chronic schizophrenia

BackgroundBoth cortisol and interleukins appear at abnormal levels in schizophrenia. Our previous study has shown that cortisol and interleukins are associated with psychopathology and response to antipsychotic medications in a relatively small sample size of patients with schizophrenia. The current study was designed to investigate how cortisol, interleukins (ILs) and their interactions would correlate with clinical presentation in a relatively large sample size of patients with schizophrenia. MethodsWe compared serum cortisol, IL-2, IL-6, and IL-8 levels in 162 medicated schizophrenia patients (including 27 patients in remission) and 62 healthy controls. Serum levels of cortisol and interleukins were measured by radioimmunoassay and quantitative ELISA, respectively. Clinical symptoms were assessed according to the Positive and Negative Syndrome Scale (PANSS). ResultsPatients with schizophrenia had significantly higher levels of cortisol and IL-2 compared to controls. Patients in remission had higher levels of IL-6 than non-remitting patients. PANSS positive symptoms, general psychopathology, cortisol and IL-2 were the most central nodes in the cortisol-IL-symptom network. The interaction between cortisol and IL-2 was associated with PANSS positive symptoms, general psychopathology and depressive factor. For patients with cortisol level above the median, IL-2 was negatively associated with PANSS positive symptoms and general psychopathology. ConclusionsOur results indicated that the interaction between cytokines and cortisol may be associated with the pathophysiology of some symptoms in chronic schizophrenia. In particular, the interaction between cortisol and IL-2 is associated with the clinical phenotypes of schizophrenia.

Deficits in odor discrimination versus odor identification in patients with schizophrenia and negative correlations with GABAergic and DNA methyltransferase mRNAs in lymphocytes.

People with schizophrenia have been reported to show deficits in tests of olfactory function. DNA methylation and GABAergic input have been implicated in biochemical processes controlling odor in animal studies, but this has not been investigated in human studies. In a study of measures of DNA methylation and GABAergic mRNAs in lymphocytes, we also measured odor identification and discrimination with the Sniffin' Sticks battery in 58 patients with chronic schizophrenia (CSZ) and 48 controls. mRNAs in lymphocytes were assessed by qPCR using TaqManTM probes. Cognition was assessed by the MATRICS battery (Measurement and Treatment Research to Improve Cognition in Schizophrenia) in CSZ and controls, and symptoms in CSZ were assessed by PANSS scale (Positive and Negative Symptom Scale). The relationships of odor deficits with mRNA, cognition, and symptoms were explored by correlation analysis. Variables which significantly differentiated CSZ from controls were explored by logistic regression. Overall, CSZ showed significantly (P≤.001) lower scores on odor discrimination compared to controls, with a moderate effect size, but no difference in odor identification. Deficits in odor discrimination, which has not been standardly assessed in many prior studies, strongly differentiated CSZ from controls. In logistic regression analysis, odor discrimination, but not odor identification, was a significant variable predicting schizophrenia versus control class membership. This is the first study to report relationship between odor deficits and DNA methylation and GABAergic mRNAs in blood cells of human subjects. There were negative correlations of odor identification with DNA methylation enzymes mRNAs and significant negative correlations with odor discrimination and GABAergic mRNAs. Lower odor scores were significantly associated with lower cognitive scores on the MATRICS battery in CSZ but not control subjects. In CSZ, lower odor scores were significantly associated with negative symptom scores, while higher odor identification scores were associated with PANNS Excitement factor. Odor discrimination was a more powerful variable than odor identification in discriminating CSZ from controls and should be used more regularly as an odor measure in studies of schizophrenia. The substantive meaning of the negative correlations of odor discrimination and GABAergic mRNA variables in peripheral lymphocytes of CSZ needs more investigation and comparison with results in neural tissue.

The efficacy of homestyle rehabilitation on negative symptoms in chronic schizophrenia: A randomized controlled trial.

Schizophrenia is a debilitating mental disorder with a high disability rate that is characterized by negative symptoms such as apathy, hyperactivity, and anhedonia that can make daily life challenging and impair social functioning. In this study, we aim to investigate the effectiveness of homestyle rehabilitation in mitigating these negative symptoms and associated factors. A randomized controlled trial was conducted to compare the efficacy of hospital rehabilitation and homestyle rehabilitation for negative symptoms in 100 individuals diagnosed with schizophrenia. The participants were divided randomly into two groups, each persisting for 3 months. The primary outcome measures were the Scale for Assessment of Negative Symptoms (SANS) and Global Assessment of Functioning (GAF). The secondary outcome measures included the Positive Symptom Assessment Scale (SAPS), Calgary Schizophrenia Depression Scale (CDSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). The trial aimed to compare the effectiveness of the two rehabilitation methods. Homestyle rehabilitation for negative symptoms was found to be more effective than hospital rehabilitation, according to the changes in SANS (T = 2.07, p = 0.04). Further analysis using multiple regression indicated that improvements in depressive symptoms (T = 6.88, p < 0.001) and involuntary motor symptoms (T = 2.75, p = 0.007) were associated with a reduction in negative symptoms. Homestyle rehabilitation may have greater potential than hospital rehabilitation in improving negative symptoms, making it an effective rehabilitation model. Further research is necessary to investigate factors such as depressive symptoms and involuntary motor symptoms, which may be associated with the improvement of negative symptoms. Additionally, more attention should be given to addressing secondary negative symptoms in rehabilitation interventions.

Range-Adaptive Value Representation in Different Stages of Schizophrenia: A Proof of Concept Study

Amotivation is related to value representation. A comprehensive account of amotivation requires a mechanistic understanding of how the brain exploits external information to represent value. To achieve maximal value discriminability, brain valuation system will dynamically adapt its coding sensitivity to the range of values available in any given condition, so-called range adaptive coding. We administered an experimental task to 30 patients with chronic schizophrenia (C-SCZ), 30 first-episode schizophrenia (FE-SCZ), 34 individuals with high social anhedonia (HSoA), and their paired controls to assess range adaptation ability. C-SCZ patients exhibited over-adaptation and their performances were negatively correlated with avolition symptoms and positive symptoms and positively correlated with blunted-affect symptoms and self-reported consummatory interpersonal pleasure scores, though the results were non-significant. FE-SCZ patients exhibited reduced adaptation, which was significantly and negatively correlated with avolition symptoms and positively correlated with the overall proportion of choosing to exert more effort. Although HSoA participants exhibited comparable range adaptation to controls, their performances were significantly and negatively correlated with the proportion of choosing to exert more effort under the lowest value condition. Our results suggest that different stages of schizophrenia spectrum showed distinct range adaptation patterns. Range adaptation impairments may index a possible underlying mechanism for amotivation symptoms in FE-SCZ and more complicated and pervasive effects on clinical symptoms in C-SCZ.

Association between empathy and clinical symptoms in chronic schizophrenia: A large sample study based on Chinese Han population

BackgroundIn patients with schizophrenia, clinical symptoms and cognitive impairment are its core features, both of which have a significant impact on the prognosis and functional outcome. Empathy, as an important social cognition, has been found to be associated with the clinical symptoms in schizophrenia, but the conclusions on this issue are inconsistent. Therefore, this study will continue to explore it through a large sample of inpatients with chronic schizophrenia in the Chinese Han population. MethodsWe obtained the sociodemographic characteristics of 987 inpatients, measured their clinical symptoms using the Positive and Negative Syndrome Scale (PANSS), and assessed their self-reported empathy using the Interpersonal Reactivity Index (IRI). The factor score for negative symptoms (FSNS) of PANSS was additionally calculated. ResultsCorrelation and linear regression analysis showed that patients' PANSS scores were widely correlated with their IRI scores. In particular, the negative symptoms of patients were significantly correlated to IRI total score (r = −0.131, p < .001) and subscales such as Perspective Taking (PT) (r = −0.233, p < .001). FSNS had close relationships with empathy as well. There are also many significant associations between other dimensions, such as general psychopathology and Perspective Taking (PT) or Fantasy (FS) (all p < .05). ConclusionsOur results indicated that clinical symptoms, especially negative symptoms, were closely related to their current empathy in patients with schizophrenia, suggesting that the severity of clinical symptoms may be a powerful factor in predicting social cognition such as empathy of schizophrenia.

A higher body mass index in Chinese inpatients with chronic schizophrenia is associated with elevated plasma orexin-A levels and fewer negative symptoms

Objective: Orexin-A is involved in numerous physiological functions, such as feeding behavior and energy balance. Yet, the associations among the orexin system, weight changes and the clinical symptoms of schizophrenia patients remain uncertain, especially in inpatients with chronic schizophrenia (CS). The purpose of this study was to investigate the relationship between the orexin-A levels, body mass index (BMI) and clinical symptoms of CS inpatients. Methods: Altogether, 324 inpatients were enrolled in our study. The clinical symptoms of all inpatients were measured using a 30-item Positive and Negative Syndrome Scale (PANSS), and then we calculated the BMI of each subject and tested the orexin-A levels by ELISA methods. Results: The orexin-A levels of the CS inpatients in the obesity group (1.24 ± 1.45 ng/ml, n = 52) were significantly higher than those in the non-overweight group (0.85 ± 1.18 ng/ml, n = 176) and the overweight group (0.97 ± 1.15 ng/ml, n = 96). Spearman’s correlation analysis showed that higher BMIs were associated with higher plasma orexin-A levels and fewer negative symptoms. Furthermore, the multiple regression analysis indicated that the orexin-A level could be a contributor to BMI (F = 30.21, p < 0.001). However, there was no correlation between plasma orexin-A concentrations and clinical symptoms in our research. Conclusion: A higher plasma orexin-A level may be a factor influencing the BMI of inpatients with CS, and fewer negative symptoms seem to be correlated with higher BMI, but the causality among BMI, orexin-A and clinical symptoms of schizophrenia requires further clinical research.

Repeated transcranial magnetic stimulation for treating the negative symptoms of schizophrenia

Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the negative symptoms of chronic schizophrenia and on the P300 component of schizophrenics′ event-related potentials (ERPs). Methods Ninety convalescing schizophrenia patients were randomly divided into a 5 Hz group, a 10 Hz group and a 15 Hz group, each of 30. The three groups were treated with the corresponding 5 Hz, 10 Hz or 15 Hz rTMS once a day, five times a week for five consecutive weeks. The P300 ERPs of all three groups were tested before and after the treatment. Any curative effect was evaluated using the scale for the assessment of negative symptoms (SANS). Results After the treatment, the average SANS score of the 10 Hz group was significantly different from that before the treatment and also from those of the other two groups after the treatment. After the treatment, significant improvement was also observed in the amplitude of P300 in the 10 Hz group. The treatment′s effectiveness was negatively correlated with age and longer course of the disease. Conclusion rTMS at 10 Hz is the most effective of the protocols tested for improving the negative symptoms of schizophrenia and improving cognitive functioning. Key words: Schizophrenia; Transcranial magnetic stimulation; Event-related potentials

Increased plasma leptin as a novel predictor for psychopathological depressive symptoms in chronic schizophrenia

BackgroundDepressive symptoms are often seen in schizophrenia. The overlap in presentation makes it difficult to distinguish depressive symptoms from the negative symptoms of schizophrenia. The adipokine leptin was found to...

T52. N-ACETYL-CYSTEINE ADD-ON TREATMENT LEADS TO AN IMPROVEMENT OF FORNIX WHITE MATTER INTEGRITY IN EARLY PSYCHOSIS

BackgroundBeneficial effects of N-acetyl-cysteine (NAC) on negative symptoms in chronic schizophrenia have been reported in two studies. A recent study in early psychosis from our group, did not report significant improvement in negative symptoms (potentially linked to the modest baseline levels) but showed improvement in cognition (i.e. processing speed) and an increase in the brain antioxidant glutathione (GSH) levels, indicating good target engagement.1 Indeed, research in animal models highlights the critical role of redox regulation by brain GSH for white matter maturation and maintenance. Given the strong evidence of white matter (WM) alterations in schizophrenia as well as the current lack of etiological treatments, redox dysregulation is an interesting target. The current study aims at investigating the impact of NAC, a precursor of GSH, the main antioxidant in the brain, on WM integrity in patients in the early psychosis phase. We focused on the fornix bundle that has been shown to be impaired in an animal model of oxidative stress2 (i.e. impaired GSH synthesis) as well as in early psychosis patients.3MethodsWM diffusion properties were estimated using generalized fractional anisotropy (gFA) computed from diffusion spectrum imaging (DSI) brain scans acquired in patients who received either NAC (n=10; mean age=25.3 ± 5.7; males/females 9/1) or placebo (n=10; mean age=24.8 ± 7.9; males/females 5/5) as add-on treatment over 6-months. GSH levels were measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (MRS).ResultsA non-parametric longitudinal voxel-based analysis limited to the fornix revealed a time x treatment interaction which reached significance in the body of the fornix (corrected p<.04) with NAC patients showing an increase in gFA over 6-month of treatment. Importantly, improvement of gFA (i.e. increase) in the fornix of early psychosis patients (NAC and placebo) correlated with increase in cerebral GSH levels (r=.67; p<.005).DiscussionThis study is the first to assess the effect of NAC on WM integrity as assessed by diffusion weighted-imaging in the early phase of psychosis. WM alterations appear early in the illness and become widespread in a more chronic phase of the disease.4 To the best of our knowledge there is currently no approved medication for schizophrenia that show significant effect on WM integrity. In this study, effects of NAC on WM integrity in the fornix were significant despite the limited sample size. This is a small-scale proof of concept study, which was very demanding for early psychosis patients and needs replication in a larger study. Its potential properties to counteract WM deficits may be even more important in individuals at clinical high risk for psychosis. As NAC add-on treatment is safe with no side effects, this study paves the way for preventive approach at the early stages of psychosis.

Distinct risk factors for obsessive and compulsive symptoms in chronic schizophrenia.

Obsessive-compulsive disorder (OCD) is common in clozapine-treated patients although the actual prevalence, phenomenology and risk factors remain unclear. The aim of the present study was to address the three aforementioned questions. The electronic records of a large cohort of clozapine-medicated schizophrenia patients routinely screened for OCD were used. The Obsessive Compulsive Inventory Revised version (OCI-R) was available from 118 cases and a 21 points cut-off threshold for OCD was defined. OCD prevalence was 47%, higher in patients on poly-pharmacy than on monotherapy (64% vs 31%; p = 0.001). Two OCI-R factors had significantly higher scores and distinct risk factors: checking behaviour (mean = 5.1; SD = 3.6) correlated with length of clozapine treatment (r = 0.21; p = 0.026), and obsessing factor (mean = 4.8; SD = 3.6) correlated with psychosis severity (r = 0.59; p = 0.001). These factors along with total OCI-R, did not correlate with either clozapine dose or plasma levels, after correcting for psychosis severity. Screening for OCD in clozapine patients, and probably in those treated with structurally similar drugs with potent antiserotoninergic properties, should be widely adopted by clinicians. Further research is needed to understand the pathophysiology underlying repetitive behavior onset in clozapine-treated patients.

Therapeutic effect of adjunctive N-acetyl cysteine (NAC) on symptoms of chronic schizophrenia: A double-blind, randomized clinical trial

BackgroundSchizophrenia is one of the most disabling psychiatric syndromes with the prevalence of 1% in the general population. Despite availability of various antipsychotics, negative symptoms and cognitive impairment are difficult to treat. In addition antipsychotic monotherapy is not effective in most of these patients. Current evidence indicates the roles of glutamatergic system in this disorder. N-acetyl cysteine (NAC) also increases extracellular glutamate. This study was conducted to evaluate the clinical effects of oral NAC as an add-on to maintenance medication for the treatment of chronic schizophrenia. Materials and methodsThis 12-week, double-blind, randomized, placebo-controlled, clinical trial was performed to determine the effectiveness of 1200mg N-acetyl cysteine as an adjunctive treatment with conventional antipsychotic medications in 84 patients with chronic schizophrenia. The subjects were evaluated with the Positive and Negative Syndrome Scale (PANSS), Mini-Mental State Examination (MMSE), and a standard neuropsychological screening test. Data were analyzed with SPSS-16 software. ResultsNAC-treated patients showed significantly improvement in the positive (F=5.47, P=0.02) and negative (F=0.20, df=1) PANSS subscale. Also the general and total PANSS score of NAC group declined over times whilst it was increased for placebo group. Regarding cognitive functions, improvement was observed in some explored areas, such as attention, short-term and working memory, executive functioning and speed of processing. There was no significant difference between the 2 groups in the frequency of adverse effects. ConclusionThe present study detected improvement in positive, negative, general and total psychopathology symptoms as well as cognitive performance with NAC treatment. It is also well-tolerated, safe and easy-to-use agent as an effective therapeutic strategy to improve outcome in schizophrenia treatment.

Treatment in early psychosis with N-acetyl-cysteine for 6 months improves low-level auditory processing: Pilot study

Sensory impairments constitute core dysfunctions in schizophrenia. In the auditory modality, impaired mismatch negativity (MMN) has been observed in chronic schizophrenia and may reflect N-methyl-d-aspartate (NMDA) hypo-function, consistent with models of schizophrenia based on oxidative stress. Moreover, a recent study demonstrated deficits in the N100 component of the auditory evoked potential (AEP) in early psychosis patients. Previous work has shown that add-on administration of the glutathione precursor N-acetyl-cysteine (NAC) improves the MMN and clinical symptoms in chronic schizophrenia. To date, it remains unknown whether NAC also improves general low-level auditory processing and if its efficacy would extend to early-phase psychosis. We addressed these issues with a randomized, double-blind study of a small sample (N=15) of early psychosis (EP) patients and 18 healthy controls from whom AEPs were recorded during an active, auditory oddball task. Patients were recorded twice: once prior to NAC/placebo administration and once after six months of treatment. The N100 component was significantly smaller in patients before NAC administration versus controls. Critically, NAC administration improved this AEP deficit. Source estimations revealed increased activity in the left temporo-parietal lobe in patients after NAC administration. Overall, the data from this pilot study, which call for replication in a larger sample, indicate that NAC improves low-level auditory processing in early psychosis.

Cilostazol adjunctive therapy in treatment of negative symptoms in chronic schizophrenia: Randomized, double-blind, placebo-controlled study.

To evaluate the efficacy and safety of cilostazol, a selective inhibitor of phosphodiesterase III, as an adjunctive to risperidone in alleviating the negative symptoms of schizophrenia. Eighty-four in-patients with diagnosis of chronic schizophrenia participated in a randomized, placebo-controlled trial and underwent 8weeks of treatment with either cilostazol (50mg twice a day) or placebo as an adjuvant to risperidone. Participants were assessed using the positive and negative syndrome scale (PANSS) at baseline and at weeks 2, 4, 6, and 8. The primary outcome measure of the trial was to evaluate the efficacy of cilostazol compared to placebo in improving the PANSS negative subscale score. General linear model repeated measures demonstrated significant effect for time×treatment interaction on negative subscale scores (p<.001) and PANSS total (p=.006) but did not demonstrate significant effect on the PANSS positive (p=.37) and general (p=.06) subscales. Frequency of adverse events was not significantly different between the 2 treatment groups. No serious adverse event was observed. An 8-week course of treatment with cilostazol as an adjunct to risperidone showed a favorable safety and efficacy profile in patients with schizophrenia.

Association between forkhead-box P2 gene polymorphism and clinical symptoms in chronic schizophrenia in a Chinese population

The forkhead-box P2 (FOXP2) gene polymorphism has been reported to be involved in the susceptibility to schizophrenia; however, few studies have investigated the association between FOXP2 gene polymorphism and clinical symptoms in schizophrenia. This study investigated whether the FOXP2 gene was associated with the development and symptoms of schizophrenia in relatively genetically homogeneous Chinese population. The FOXP2 rs10447760 polymorphism was genotyped in 1069 schizophrenia inpatients and 410 healthy controls using a case-control design. The patients' psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). We found no significant differences in the genotype and allele distributions between the patient and control groups. Interestingly, we found significant differences in PANSS total, positive symptom, and general psychopathology scores between genotypic subgroups in patients, with the higher score in patients with CC genotype than those with CT genotype (all p<0.05). After adjusting demographic and clinical variables, the difference still remained significant for the PANSS positive symptom score and general psychopathology (both p<0.05). Our findings suggest that the FOXP2 rs10447760 polymorphism may not contribute to the development of schizophrenia, but may contribute to the clinical symptoms of schizophrenia among Han Chinese.

M4. Epigeneticly Related mRNA Levels in Lymphocytes of Schizophrenic and Nonpsychotic Controls

Background: Epigenetic dysregulation may be involved in the underlying molecular deficits in schizophrenia (SZ). Previous research by our group has show hypermethylation of GABAergic promoter gene in and increases in DNMT1 and DNMT3A in post mortem brain samples of patients with SZ. We have also shown that difference sin DNMT1 and other epigenetically related enzymes are also found in the lymphocytes of living patients with chronic schizophrenia (CSZ). We now report preliminary results on epigenetic related mRNA’s in lymphocytes on a larger sample of CSZ. Methods: CSZ (n = 29) and nonpsychotic controls (NPC) (n = 31) subjects had a blood sample (60–80 cc) drawn, and lymphocyte pellet extracted by Ficoll gradient procedure. qPCR assays were used to measure epigenetically related mRNA’s—DNMT1, DMNT3A, TET1, TET2, TET3, BDNF, NR3C (glucocorticoid receptor).We also assayed several immunological related mRNA (which appeared as strong hits from RNA sequence analysis) T-Cell Surface Glycoprotein CD4, CCR1 (C-C motif chemokine receptor 1), FPRL3 (Formyl Peptide Receptor). Assays were performed using Taqman probes with B-Actin as housekeeping gene. Patients were also evaluated with psychopathology with PANSS, for cognitive function with MATRICS, and for odor identification and discrimination with Sniff and Sticks smell test. Results: In this sample CSZ showed significantly higher DMNT3A (P = .048) than NPC Male CSZ showed significantly higher DNMT1 than NPC (P = .014), but the total sample there was a trend but no significant difference in DNMT1. Compared to NPC, CSZ subjects showed significantly higher levels of GABAergic enzymes measured by the GAD1 probe (which assays GAD67 and GAD25 mRNA) (P = .030), higher levels of glucocorticoid receptor measured by the NRC3 probe (P = .006), and significantly lower levels of FRPRL3(P = .039). Higher levels FPRL3 and CD4 were moderately correlated with PANSS positive symptoms in CSZ (FRPL3 r = +.43 P = .019, CD4 r = +.37 P = .054) and these correlations were slightly stronger in male CSZ. Higher DNMT1 and DNMT3A levels in lymphocytes of CSZ correlated negatively with scores n MATRICs battery (DNMT1—attention/vigilance—r = −.41, P = .031, working memory r = −.37, P = .048, composite score r = −.36, P = .063). Conclusion: CSZ demonstrate differences in epigenetically related mRNA’s in their lymphocytes. In CSZ higher levels of DNMT were related to poorer cognitive performance and higher levels of immunological related mRNA to greater positive symptom scores. Some potential differences to our previously published results may be related to differences in mRNA’s measured by the Taqman probes and earlier research with specifically generated sequence probes.