Symptoms In Schizophrenic Patients Research Articles

Poor insight and psychosis

A variety of phenomena might be considered as reflecting impaired insight in psychosis, like failure to recognize signs, symptoms or disease, failure to derive appropriate cognitive representations, despite recognition of the disease, and misattribution of the source or cause of the disease. The unawareness of tardive dyskinesia symptoms in schizophrenic patients points that self-awareness deficits in schizophrenia may be domain specific. Poor insight is an independent phenomenological and a prevalent feature in psychotic disorders in general, and in schizophrenia in particular, but we don't know yet if delusions in schizophrenia are the result of an entirely normal attempt to account for abnormal perceptual experiences or a product of abnormal experience but of normal reasoning. The theoretical approaches regarding impaired insight include the disturbed perceptual input, the impaired linkage between thought and emotion and the breakdown of the process of self-monitoring and error checking. The inability to distinguish between internally and externally generated mental events has been described by the metarepresentation theory. This theory includes the awareness of ones' goals, which leads to disorders of willed action, the awareness of intention, which leads to movement disorders, and the awareness of intentions of others, which leads to paranoid delusions. The theory of metarepresentation implies mainly output mechanisms, like the frontal cortex, while the input mechanism implies posterior brain systems, including the parietal lobe. There are many similarities between the disturbances of awareness seen in schizophrenia and those seen as a result of known neurological impairment. Neuropsychological models of impaired insight typically attribute the disturbance to any of a variety of core deficits in the processing of information. In this respect, lack of insight is on conceptual par with alogia, apraxia or aphasia in reflecting disturbed cognitive processing. In this direction, research have implicated the role of self-monitoring in disorders of awareness and many of the core symptoms of schizophrenia, and has been suggested that these symptoms are the result of a disturbance of a medial frontal system involving anterior hippocampus, cingulated gyrus, supplementary motor area, and dorsolateral prefrontal cortex. Poor insight seems to be something more than a symptom or an epi-phenomenon and its mechanism may constitute a core factor into the psychosis process. Also, poor insight would be involves a common mechanism for many other mental disorders or even it would be an independent and trans-diagnostic factor into the human personality, probably like the dimension of psychotism.

Depressive symptoms in schizophrenia and dopamine and serotonin gene polymorphisms

Although depressive symptoms seem to be frequent in schizophrenia they have received significantly less attention than other symptom domains. As impaired serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis of depression and schizophrenia this study sought to investigate the putative association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this study were to closely examine schizophrenia symptom domains by performing factor analysis of the two most used instruments in this setting (Positive and negative syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine the influence of investigated gene polymorphisms on the schizophrenia symptom domains, focusing on depressive scores. A total of 591 participants were included in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%) of schizophrenic patients had significant depressive symptoms. Genotype distribution revealed no significant differences regarding all investigated polymorphisms except the separate gender analysis for MAO-A gene polymorphism which revealed significantly more allele 3 carriers in schizophrenic males. Factor analysis of the PANSS scale revealed the existence of five separate factors (symptom domains), while the CDSS scale revealed two distinct factors. Several investigated gene polymorphisms (mostly SERT and MAO-A, but also COMT) significantly influenced two factors from the PANSS (aggressive/impulsive and negative symptoms) and one from the CDSS scale (suicidality), respectively. Depressive symptoms in schizophrenic patients may be influenced by functional gene polymorphisms, especially those implicated in serotonergic neurotransmission.

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.

Schizophrenia and smoking: impact on negative symptoms

Introduction: it has been hypothesized that individuals with schizophrenia use nicotine to reduce negative symptoms and improve cognitive function. There is an inconsistency in the literature suggesting that nicotine could help decrease negative symptoms in schizophrenic patients. Objective: to investigate the effects of nicotine on the expression of the negative symptoms in smokers and non-smokers with schizophrenia. Methods: a cross sectional study, conducted between April and August 2016, 100 inpatients with schizophrenia (54 smokers and 46 non-smokers) diagnosed according to DSM-V, at Psychiatric Hospital of the Cross Lebanon, were compared to changes in clinical parameters using CDSS, PANSS, and nicotine dependence using FTND. The Student’s t-test was used to compare between 2 groups, while the ANOVA test was used to compare between 3 or more groups. For categorical variables, the chi-2 test was used. Results: the mean age was 47.16 years (SD = 7.14) for smokers compared to 47.02 years (SD = 7.92) for non-smokers. 64.8% of smokers were males versus 45.7% of non-smokers. Smoking (high nicotine dependence) significantly decreases the PANSS negative symptoms score between the 2 groups (p < .001), whereas it did not show a significant difference for the positive and the cognitive symptoms total score (p > .05 for both variables). Discussion and conclusion: this study is the first to investigate the relationship between the expression of negative symptoms in individuals with schizophrenia and smoking in Lebanon. Cigarette smoking rates remain remarkably high in patients with schizophrenia. Smoking is a complex process which involves psychopathological, biochemical and neuropharmacological aspects among schizophrenic patients. Further studies are needed to acknowledge these findings and the reasons behind it.

Positive changes in the severity of residual psychotic symptoms in schizophrenic patients switched to treatment with risperidone

To evaluate the effect of changing therapy from typical antipsychotics to the atypical antipsychotic risperidone in the treatment of difficult-to-treat residual psychotic symptoms. The study included 15 patients, 8 men and 7 women, mean age 49.1±10.25 years, diagnosed with paranoid schizophrenia, partial remission (ICD-10 F20.04). At the beginning all participants received regular maintenance antipsychotic therapy with typical antipsychotics. The patient assessment with the PANSS, CGI scale and GAF scale was performed at the beginning (before the change of antipsychotics to risperidone) and in the end of the study. The primary efficacy endpoint was a reduction in scores on the PANSS items P1 'delusions' and P3 'hallucinatory behavior' to 1 (no such symptom) or 2 (minimal residual symptom). Secondary criteria were positive changes in the severity of other psychopathological symptoms and an increase in the social functioning level. The average dose of risperidone was 4.62±1.35 mg. The duration of treatment was 2 month. After switching from typical antipsychotics to risperidone and two months monotherapy, there were significant positive changes in the total PANSS score as well as in positive subscale score and CGI-S score. The small, but statistically significant, changes were detected in the overall functioning of the patients (the increase in the GAF score). The dynamics of residual psychotic symptoms was unequal: the severity of hallucinatory symptoms decreased significantly while the delusional symptoms remained unchanged. The authors suggest that excessive dopaminergic blockade might play a significant role in the pathogenesis of residual symptoms. This fact may explain the positive effect of treatment in the cases with the less degree of dopaminergic blockade. If it is true, the treatment strategy in the maintenance phase should not be a direct continuation of acute phase therapy and switching to other drugs and changing of the dose are needed.

Effectiveness of Vitamin D Supplement Therapy in Chronic Stable Schizophrenic Male Patients: A Randomized Controlled Trial.

In this study, the aim was to determine whether adding vitamin D to the standard therapeutic regimen of schizophrenic male patients with inadequate vitamin D status could improve some aspects of the symptom burden or not. This study was an open parallel label randomized clinical trial. Eighty patients with chronic stable schizophrenia with residual symptoms and Vitamin D deficiency were recruited randomly and then received either 600000 IU Vitamin D injection once along with their antipsychotic regimen or with their antipsychotic regimen only. Serum vitamin D was measured twice: first at the baseline and again on the fourth month. Positive and Negative Syndrome Scale (PANSS) was assessed at the baseline and on the fourth month. During the study, the vitamin D serum changes in vitamin group and control group were 22.1 ± 19.9(95%CI = 15.9-28.8) and 0.2 ± 1.7(95%CI = 0.2-0.8) (ng/mL) (p<0.001) respectively. The changes of PANSS positive subscale score (P) were -0.1±0.7 (95%CI =-0.3-0.1) and 0.00 ± 0.8 (95%CI = -0.2-0.2) in vitamin D and control group respectively (p=0.5). The changes of PANSS negative subscale score (N) were -0.1 ± 0.7 (95%CI = -0.3-0.05) and -0.1 ± 0.5 (95%CI = -0.2-0.04) in vitamin D and control group respectively (p = 0.7) and there was a negative but not significant correlation between serum vitamin D level changes and PANSS negative subscale score (r = -0.04, p = 0.7). We did not find a relationship between serum vitamin D level changes and the improvement of negative and positive symptoms in schizophrenic patients and more randomized clinical trials are required to confirm our findings.

Effects of internalized stigma on symptoms and quality of life in schizophrenic patients; mediated by dysfunctional attitude

The objective of this study was to determine the effects of internalized stigma on symptoms, quality of life of schizophrenic patients; mediated by dysfunctional attitude. A descriptive correlational research design was used to investigate the relationship between symptoms, quality of life and dysfunctional attitude in schizophrenic patients. Linear regression was used to investigate the mediational effects of dysfunctional attitude. Purposive sampling technique was used for the selection of the participants. The study was conducted on diagnosed schizophrenic patients from psychiatry ward of Nishtar Hospital Multan, Fountain House Rehabilitation Centre Lahore and Punjab Institute of Mental Health Rehabilitation Centre Lahore. The sample of the study was 50 registered patients of schizophrenia. Calculated sample size was 50 schizophrenic patients among them 34 were Males and 16 were Females. Internalized Stigma of Mental Illness Scale was used to see the effects of stigma on schizophrenic patients (ISMI, Ritsher, 2003), along with Positive and Negative Syndrome Scale was used to evaluate the positive and negative symptoms in schizophrenic patients (Kay, et al., 1987), World Health Organization Quality of life BREF Scale (WHOQOL-BREF, 2003) was used to assess the quality of life of schizophrenic patients, along with another scale of Dysfunctional Attitude Scale (DAS, Weissman, 1978) was also used to assess the cognitive functioning of the schizophrenic patients. Studies showed that internalized stigma had significant positive correlation with dysfunctional attitude and negative significant correlation with symptoms and quality of life of schizophrenic patients. Internalized stigma had strong significant effects on the symptoms, quality of life and dysfunctional attitude. Studies also showed that people with mental illness has to face negative stereotype, rejection and finally alienation from society because of stigma which is a big hurdle in their process of recovery and treatment.

PT624. Clinical profiles of obsessive compulsive symptoms in schizophrenic patients

PT624. Clinical profiles of obsessive compulsive symptoms in schizophrenic patients

Association of EPHB1 rs11918092 and EFNB2 rs9520087 with psychopathological symptoms of schizophrenia in Chinese Zhuang and Han populations.

Two single-nucleotide polymorphisms (SNPs) (rs11918092 and rs9520087) were genotyped in Chinese Zhuang and Han populations. Symptoms of schizophrenic patients were assessed by the Positive and Negative Syndrome Scale. No association of any SNP with schizophrenic susceptibility was found. However, associations of rs9520087 with the total scale score (P = 0.014), positive scale score (P = 0.013), negative scale score (P = 0.032), and general psychopathology scale score (P = 0.031) were found in Zhuang patients. Additionally, rs11918092 was associated with positive scale score (P = 0.035) in Han patients. The two SNPs might influence symptoms of schizophrenia.

Platelet serotonin concentration and depressive symptoms in patients with schizophrenia

Depressive symptoms seem to be frequent in schizophrenia, but so far they have received less attention than other symptom domains. Impaired serotonergic neurotransmission has been implicated in the pathogenesis of depression and schizophrenia. The objectives of this study were to investigate platelet serotonin concentrations in schizophrenic patients with and without depressive symptoms, and to investigate the association between platelet serotonin concentrations and symptoms of schizophrenia, mostly depressive symptoms. A total of 364 patients were included in the study, 237 of which had significant depressive symptoms. Significant depressive symptoms were defined by the cut-off score of 7 or more on Calgary Depression Rating Scale (CDSS). Platelet serotonin concentrations were assessed by the enzyme-linked immunosorbent assay (ELISA). Prevalence of depression in patients with schizophrenia was 65.1%. Schizophrenic patients with depressive symptoms showed lower platelet serotonin concentrations (mean±SD; 490.6±401.2) compared to schizophrenic patients without depressive symptoms (mean±SD; 660.9±471.5). An inverse correlation was established between platelet serotonin concentration and depressive symptoms, with more severe symptoms being associated with lower platelet serotonin concentrations. Depressive symptoms in schizophrenic patients may be associated with reduced concentrations of platelet serotonin.

Depressive symptoms in a sample of patients diagnosed with schizophrenia

IntroductionPrevious studies highlight the difficulty of correctly diagnosing depressive symptoms in schizophrenic patients, as well as the impact on clinical progression among patients who present with both syndromes, worsening treatment adherence and overall prognosis.AimsTo determine the prevalence of depressive symptoms in patients diagnosed with schizophrenia. To analyze the relationship of depressive symptoms with other demographic and clinical variables.Material and methodsEighty-four patients diagnosed with schizophrenia according to ICD-10 criteria and treated in an Outpatient Mental Health Clinic were recruited for this study. Symptom severity was assessed using The Positive and Negative Syndrome Scale (PANSS; Kay et al., 1987); classifying patients as positive, negative or mixed schizophrenia subtypes. Data from clinical and sociodemographic variables was obtained from clinical records.ResultsThe mean age was 43.2 years (SD: 10.2). Depression is objectively detected in 10.3% of the sample, and presented as subjective depression in 29.5%. The prevalence of depressive symptoms is higher among women, unmarried patients, lower social classes and patients who met criteria for predominantly positive Schizophrenia subtype. Higher prevalence of depressive symptoms was found in patients with a shorter course of disease.ConclusionsDepressive symptoms present with a high prevalence among patients diagnosed with schizophrenia, especially during the early years of the disease. Given the severe impact of depression on both the evolution and prognosis of patients with severe mental illness, screening and early treatment must be carried out.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Antipsychotic Treatment in Pluripathology

Is well known some organic diseases produce psychotic symptoms. Association between HIV and presence of psychopathology is highly prevalent. For this reason, a case report of HIV, liver cirrhosis, drug abuse and psychotic disorder is presented below. The patient was a 46 year old male infected by HIV and liver cirrhosis (Child-Pugh B) secondary to HCV infection. He had had psychiatric history of major depressive disorder, cannabis use disorder, alcohol use disorder, cocaine use disorder and heroin use disorder. Without consume of heroin, cocaine and alcohol during last 5 years. He was in treatment with methadone, benzodiazepines and antiretroviral treatment. In 2013 the patient suffered a psychotic episode with an important affective and behavioral repercussion and he was admitted in an acute unit of psychiatry. It was necessary a pharmacological treatment with a limited hepatic metabolism because of his liver cirrhosis and potential drug interactions with antiretroviral treatment and methadone. So that, it was decided to use oral Paliperidone (9 mg/day), achieving a remission of psychotic symptomatology. In this case Paliperidone was safe, without side effects and good tolerance. Liver function was preserved and CD4 levels remained undetectable. In patients with severe mental illness and concomitant organic disease, complexity of treatment is a determining factor in therapeutic decisions. In conclusion, Paliperidone could be considered sure to treat psychotic symptoms in schizophrenic patients who use others medications with hepatic metabolism, drug interactions, and mild to moderate liver failure.

Relationship between Antidepressant Prescription Rates and Features of Schizophrenic Patients and Its Outcome in Schizophrenia Treatment

Comorbid depression in schizophrenia is associated with poor outcome, increased risk of relapse and a high rate of suicide. Identification of depressive symptoms and their appropriate treatment is crucial for depressed schizophrenic patients. The aim of this study is to investigate the rates of antidepressant prescription and their outcomes. The records of the schizophrenic outpatients, who were consulted at Psychosis Unit of Psychiatry Department between January 2007 and September 2012, were evaluated retrospectively. Enrolled schizophrenic patients' antidepressant medications were at their minimal effective doses and effective duration. The present study demonstrates that 39 of the 101 patients during their follow-ups were prescribed antidepressants. The mean follow-up period was 6.3 (±4.2) years; the mean age at onset was 22 (±6.5) years; the mean duration of illness was 14.7 (±7.3) years and the mean number of psychotic exacerbation was 5 (±3.7). The most prescribed antidepressants were; sertraline (36.9%), venlefaxine (23.8%) and essitalopram (20.2%). SSRI's were prescribed 57 (73.1%), where as SNRI's 21 times (26.9%). There was no significant difference between SSRI (78.6%) and SNRI (21.4%) treatments in terms of psychotic exacerbation under antidepressant medication. Full remission of depressive symptoms was achieved in 21 patients (53.8%). Remission rates were significantly higher (p<0.01) in SNRI treated depressed schizophrenic patients (85.7%) compared to SSRI treated patients (50.9%). In 8 of the 39 patients (20.5%) antidepressant treatment was terminated due to side effects. This study demonstrates that SSRI's were more often prescribed compared to other classes of antidepressants in emerging depressive symptoms in schizophrenic patients despite full remission with SNRI's is more common. There was no significant difference between SSRI and SNRI treatment in terms of psychotic exacerbation.

Nitroprusside single-dose prevents the psychosis-like behavior induced by ketamine in rats for up to one week

Recently, we found a rapid and long-lasting improvement of symptoms in schizophrenic patients on antipsychotics after a single four-hour infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor with a short half-life. This improvement persisted for up to 4weeks. Because these patients remained on antipsychotics after infusion of SNP was finished, the question arises about whether this improvement was due to SNP itself. We have now investigated whether SNP, alone, can produce preventive antipsychotic effects in rats treated with ketamine (KET). 56 adult rats divided into 7 groups were infused with SNP 4mg/kg, KET 25mg/kg, or saline as follows: group1 — saline, group2 — SNP, group3 — KET, group4 — KET 12h after SNP, group5 — KET 1day after SNP, group6 — KET 2days after SNP, and group7 — KET 1week after SNP. The animals were filmed in an open field arena for 30min and the videos were later analyzed by ANY-Maze software to measure activity and stereotypy. SNP significantly prevented the emergence of hyperactivity induced by KET when it was administered for up to 1week before KET, and prevented the emergence of stereotypies when it was administered for up to 1day before KET. These findings in rats, which have an even faster metabolic rate than humans, suggest that the long-lasting effects observed in our clinical trial with SNP in humans could have been due to SNP itself, and indicate for the first time that SNP may present preventive antipsychotic effects.

Multivariate Analysis of Relationship between Childhood Trauma and Psychotic Symptoms in Patients with Schizophrenia.

The aim of this study was to examine the relationship between childhood trauma and psychotic symptoms in schizophrenic patients after controlling for the possible confounding factors, such as depression and dissociative symptoms. Ninety-eight schizophrenic inpatients participated. Childhood trauma was examined using the Childhood Trauma Questionnaires (CTQ), which consists of physical abuse (PA), sexual abuse (SA), emotional abuse (EA), physical neglect (PN), and emotional neglect (EN). Positive and Negative Syndrome Scale (PANSS), Dissociative Experience Scale (DES), and Beck's Depression Inventory (BDI) were also administered. Data were analyzed by partial correlation and general linear model. The total score of CTQ was positively correlated with positive, general, and total scores of PANSS. All five types of childhood trauma were associated with dissociative symptoms. EA and EN were positively correlated with depressive symptoms. Only SA significantly predicted positive symptoms of schizophrenia after controlling for age, sex, BDI, and DES scores, with a dose-response relationship between SA and positive symptoms.

Neuropsychological and cerebral morphometric aspects of negative symptoms in schizophrenia: negative symptomatology is associated with specific mnestic deficits in schizophrenic patients.

BackgroundThe prevalence of negative symptoms in schizophrenic patients seems to be an important indicator for treatment response and prognosis. Although negative symptoms have often been attributed to frontal lobe anomalies, neuropsychological and anatomical findings do not explicitly support this assumption. Since knowledge about the cerebral correlate of negative symptoms in schizophrenia might have a strong impact on therapeutic and psychopharmacological interventions, we aimed to answer this question by investigating the relationship between negative symptoms, neuropsychological functioning and cerebral volumes in schizophrenic patients.MethodsTwenty schizophrenic patients and 32 healthy controls were examined using a neuropsychological test battery for the assessment of temporal (mnestic) and frontal (executive) faculties. Volumetric measurements of temporal (hippocampus and amygdala) and frontal (orbitofrontal, dorsolateral prefrontal, and anterior cingulate area) brain areas were performed. Negative symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS).ResultsSchizophrenic patients performed worse than healthy controls in tests assessing verbal and visuospatial learning and memory functions and on the Stroop interference task. After dividing the schizophrenic group in patients with high and low SANS scores almost all of these deficits were restricted to the former group. There were no overall group differences regarding cerebral subarea volumes. Overall negative symptoms were significantly correlated with verbal memory functions but not with frontal lobe faculties.ConclusionsNegative symptoms in schizophrenia could specifically associated with verbal memory deficits.

PCP-induced deficits in murine nest building activity: Employment of an ethological rodent behavior to mimic negative-like symptoms of schizophrenia

Schizophrenia is a severe psychiatric disorder characterized by three symptom domains, positive (hallucinations, obsession), negative (social withdrawal, apathy, self-neglect) and cognitive (impairment in attention, memory and executive function). Whereas current medication ameliorates positive symptomatology, negative symptoms as well as cognitive dysfunctions remain untreated. The development of improved therapies for negative symptoms has proven particularly difficult, in part due to the inability of mimicking these in rodents. Here, we address the predictive validity of combining an ethologically well preserved behavior in rodents, namely nest building activity, with an established animal model of schizophrenia, the sub-chronic PCP model, for negative symptoms. Decline in rodent nesting activity has been suggested to mirror domains of negative symptoms of schizophrenia, including social withdrawal, anhedonia and self-neglect, whereas repeated treatment with the NMDAR antagonist PCP induces and exacerbates schizophrenia-like symptoms in rodents and human subjects. Using a back-translational approach of pharmacological validation, we tested the effects of two agents targeting the nicotinic α7 receptor (EVP-6124 and TC-5619) that were reported to exert some beneficial effect on negative symptoms in schizophrenic patients. Sub-chronic PCP treatment resulted in a significant nest building deficit in mice and treatment with EVP-6124 and TC-5619 reversed this PCP-induced deficit. In contrast, the atypical antipsychotic drug risperidone remained ineffective in this assay. In addition, EVP-6124, TC-5619 and risperidone were tested in the Social Interaction Test (SIT), an assay suggested to address negative-like symptoms. Results obtained in SIT were comparable to results in the nest building test (NEST). Based on these findings, we propose nest building in combination with the sub-chronic PCP model as a novel approach to assess negative-like symptoms of schizophrenia in rodents.

The Interaction of Polymorphisms of IL10 and DBH Was Associated with General Symptoms of PANSS with TD in Chinese Han Schizophrenic Patients

ObjectiveTardive dyskinesia (TD) is a human hyperkinetic movement disorder as a result of potentially irreversible long-term chronic first-generation antipsychotic medications. Unfortunately, mechanisms involved in the development of TD have been poorly understood. Previous studies have indicated that some genetic polymorphisms of immune system and dopamine beta-hydroxylase (DBH) genes may be involved in the pathogenesis of TD. Rs1800872 and rs72393728 are located on the promoter of interleukin-10 (IL10) and DBH gene, respectively. The genetic association between the rs1800872 and TD is unclear. Previous studies have indicated that genetic variations of IL 10 and DBH are implicated in the positive and negative symptoms in schizophrenia. However, the interaction of two variations with severity of TD and symptoms of schizophrenic patients with TD has not been reported. The present study investigated whether these variations and their interaction were associated with clinical phenotypes of TD with schizophrenia in a genetically homogeneous northern Chinese Han population.MethodsRs1800872 and rs72393728 were genotyped in schizophrenic patients with TD (n = 372) and without TD (NTD; n = 412). The Abnormal Involuntary Movement Scale (AIMS) and Positive and Negative Syndrome Scale (PANSS) were applied to assess the severity of TD and psychopathology of schizophrenia, respectively.ResultsThe allele and genotype frequencies of rs1800872 and rs72393728 did not significantly differ between TD and NTD patients (p>0.05). No significant difference was found in the AIMS total score among the genotypes of two loci (p>0.05). Interestingly, the interaction of rs1800872 and rs72393728 showed a significant association with the PANSS general score (p = 0.011), and a trend toward to the PANSS total score (p = 0.055).ConclusionThese findings suggest that the interaction of rs1800872 and rs72393728 variants may play a role in psychopathology of the general symptoms on PANSS in schizophrenic patients with TD in a northern Chinese Han population.

Glutamatergic Dysbalance and Oxidative Stress in In Vivo and In Vitro Models of Psychosis Based on Chronic NMDA Receptor Antagonism

BackgroundThe psychotomimetic effects of N-methyl-D-aspartate (NMDA) receptor antagonists in healthy humans and their tendency to aggravate psychotic symptoms in schizophrenic patients have promoted the notion of altered glutamatergic neurotransmission in the pathogenesis of schizophrenia.MethodsThe NMDA-receptor antagonist MK-801 was chronically administered to rats (0.02 mg/kg intraperitoneally for 14 days). In one subgroup the antipsychotic haloperidol (1 mg/kg) was employed as a rescue therapy. Glutamate distribution and 3-NT (3-nitrotyrosine) as a marker of oxidative stress were assessed by immunohistochemistry in tissue sections. In parallel, the effects of MK-801 and haloperidol were investigated in primary embryonal hippocampal cell cultures from rats.ResultsChronic NMDA-R antagonism led to a marked increase of intracellular glutamate in the hippocampus (126.1 +/− 10.4% S.E.M of control; p = 0.037), while 3-NT staining intensity remained unaltered. No differences were observed in extrahippocampal brain regions. Essentially these findings could be reproduced in vitro.ConclusionThe combined in vivo and in vitro strategy allowed us to assess the implications of disturbed glutamate metabolism for the occurrence of oxidative stress and to investigate the effects of antipsychotics. Our data suggest that oxidative stress plays a minor role in this model than previously suggested. The same applies to apoptosis. Moreover, the effect of haloperidol seems to be mediated through yet unidentified mechanisms, unrelated to D2-antagonism. These convergent lines of evidence indicate that further research should be focused on the glutamatergic system and that our animal model may provide a tool to explore the biology of schizophrenia.

BDNF Val66Met polymorphism and anxiety/depression symptoms in schizophrenia in a Chinese Han population

Although several lines of evidences suggest that the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may be involved in the pathophysiology of schizophrenia, this association remains controversial. Here, we aim to investigate the genetic association between the BDNF Val66Met polymorphism and schizophrenia and to explore whether this polymorphism could influence the severity of clinical symptoms in schizophrenic patients in a Chinese Han population. Genotyping of the BDNF Val66Met polymorphism was carried out in 456 schizophrenic patients and 483 controls using the fluorescence resonance energy transfer method. The patients' psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. The general clinical data of schizophrenic patients were analyzed. There were significant differences in the genotype distribution and allelic frequencies of the BDNF Val66Met polymorphism between the schizophrenia group and the controls. Multiple linear regression analysis showed that the BDNF Val66Met polymorphism explained ~16% of the variance in anxiety/depression symptoms in schizophrenic patients. Our data provide evidence that the BDNF Val66Met polymorphism may be involved in the etiology of schizophrenia in a Chinese Han population. Furthermore, the BDNF Val66Met polymorphism is a significant factor influencing the severity of anxiety/depression symptoms in schizophrenic patients.