Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a serious health issue for many patients with schizophrenia. There is a lack of predictors for and understanding of the development of obesity in the early phase of the illness. Therefore we investigated a set of routine biochemistry variables in blood as predictors of the development of obesity and weight gain over 5 years in an observational cohort study of patients with first-episode schizophrenia (n=59). Twelve percent of the patients were obese at baseline and 37% were obese at the 5-year follow-up. The mean body mass index (BMI) change over 5 years was a 4.1 kg/m(2) increase (4.5 SD). Obesity was predicted by baseline hemoglobin levels (odds ratio per standard deviation [OR/SD] 3.3, 95% confidence interval [CI] 1.4 to 7.5), red blood cell count (OR/SD 2.6, 95% CI 1.2 to 5.5), hematocrit (OR/SD 2.8, 95% CI 1.3 to 5.9), gamma-glutamyltransferase (OR/SD 2.8, 95% CI 1.2-6.3) and creatinine (OR/SD 3.1, 95% CI 1.2 to 8.0). After adjustment for baseline BMI, the associations were attenuated for gamma-glutamyltransferase and creatinine. Low baseline BMI was associated with a greater BMI increase. The major conclusion is that easily available routine biochemistry markers can be useful in predicting the development of obesity in first-episode schizophrenia. The mechanisms underlying the observed associations are unknown, but the predictors identified in this study could signify dehydration or insulin resistance. These observations open a new window to future research on the mechanisms underlying the development of obesity in schizophrenia.
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PMID:Biochemical risk factors for development of obesity in first-episode schizophrenia. 1984 78

While psychiatric disorders such as schizophrenia are largely diagnosed on symptomatology, several studies have attempted to determine which biomarkers can discriminate schizophrenia patients from non-patients with schizophrenia. The objective of this study is to assess whether near-infrared spectroscopy (NIRS) measurement can distinguish schizophrenia patients from healthy subjects. Sixty patients with schizophrenia and sixty age- and gender-matched healthy controls were divided into two sequential groups. The concentration change in oxygenated hemoglobin (Delta[oxy-Hb]) was measured in the bilateral prefrontal areas (Fp1-F7 and Fp2-F8) during the Verbal Fluency Test (VFT) letter version and category version, Tower of Hanoi (TOH), Sternberg's (SBT) and Stroop Tasks. In the first group, schizophrenia patients showed poorer task performance on all tasks and less prefrontal cortex activation during all but the Stroop Task compared to healthy subjects. In the second group, schizophrenia patients showed poorer task performance and less prefrontal cortex activation during VFTs and TOH tasks than healthy subjects. We then performed discriminant analysis by a stepwise method using Delta[oxy-Hb] and task performance measures as independent variables. The discriminant analysis in the first group included task performance of TOH, VFT letter and VFT category and Delta[oxy-Hb] of VFT letter. As a result, 88.3% of the participants were correctly classified as being schizophrenic or healthy subjects in the first analysis. The discriminant function derived from the first group correctly assigned 75% of the subjects in the second group. Our findings suggest that NIRS measurement could be applied to differentiate patients with schizophrenia from healthy subjects.
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PMID:Discriminant analysis in schizophrenia and healthy subjects using prefrontal activation during frontal lobe tasks: a near-infrared spectroscopy. 1989 32

Understanding individual differences in the susceptibility to metabolic side effects as a response to antipsychotic therapy is essential to optimize the treatment of schizophrenia. Here, we perform genomewide association studies (GWAS) to search for genetic variation affecting the susceptibility to metabolic side effects. The analysis sample consisted of 738 schizophrenia patients, successfully genotyped for 492K single nucleotide polymorphisms (SNPs), from the genomic subsample of the Clinical Antipsychotic Trial of Intervention Effectiveness study. Outcomes included 12 indicators of metabolic side effects, quantifying antipsychotic-induced change in weight, blood lipids, glucose and hemoglobin A1c, blood pressure and heart rate. Our criterion for genomewide significance was a pre-specified threshold that ensures, on average, only 10% of the significant findings are false discoveries. A total of 21 SNPs satisfied this criterion. The top finding indicated that a SNP in Meis homeobox 2 (MEIS2) mediated the effects of risperidone on hip circumference (q=0.004). The same SNP was also found to mediate risperidone's effect on waist circumference (q=0.055). Genomewide significant finding were also found for SNPs in PRKAR2B, GPR98, FHOD3, RNF144A, ASTN2, SOX5 and ATF7IP2, as well as in several intergenic markers. PRKAR2B and MEIS2 both have previous research indicating metabolic involvement, and PRKAR2B has previously been shown to mediate antipsychotic response. Although our findings require replication and functional validation, this study shows the potential of GWAS to discover genes and pathways that potentially mediate adverse effects of antipsychotic medication.
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PMID:Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs. 2019 66

Cognitive impairments are considered as a core feature of schizophrenia and have been reported in associated with dysfunction of the prefrontal cortex (PFC). The Tower of London (TOL) task is a widely used neuropsychological test to assess the planning ability and the PFC function. In the present study, we examined functional changes in the PFC of 40 first-episode schizophrenia patients and 40 age- and gender-matched healthy controls by means of multi-channel Near-infrared spectroscopy (NIRS) during performance of the TOL task. NIRS is a noninvasive optical method that can measure relative changes in oxygenated ([oxy-Hb]) and deoxygenated ([deoxy-Hb]) hemoglobin in cortical tissue. Compared to the healthy controls, schizophrenia patients exhibited a significant decreased activation in the left PFC and poorer TOL performance. The results confirm the functional deficits of the PFC and impaired planning ability in first-episode schizophrenia patients and suggest that NIRS may be a useful clinical tool for evaluating PFC activation in psychiatric disorders.
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PMID:Reduced prefrontal activation during Tower of London in first-episode schizophrenia: a multi-channel near-infrared spectroscopy study. 2045 17

Relationships between deficits in verbal fluency and poor social functioning have been revealed in patients with schizophrenia. In previous studies, we demonstrated that deficits in idea fluency, which is ranked as a more complex type of verbal fluency and reflects divergent thinking ability, were more closely related to social dysfunction than deficits in simple word fluency. Although functional neuroimaging studies have provided detailed data regarding prefrontal dysfunction during word fluency tasks, the regions that relate to deficits in fluency of ideas and thoughts have not yet been clarified in schizophrenia patients. The purpose of the present study was to identify the prefrontal sub-regions responsible for deficits in idea fluency using near-infrared spectroscopy (NIRS), which is more practical than other imaging methods, and to investigate the relationships between lesions and idea fluency deficits and social dysfunction in patients with schizophrenia. Eighteen outpatients with schizophrenia and 16 healthy subjects were recruited for this case-controlled study. Using 24-channel NIRS, we measured changes in hemoglobin concentration in the prefrontal cortical surface area during idea and letter fluency tests. The analyses revealed that schizophrenia patients generally exhibited a smaller increase in the concentration of oxyhemoglobin in the frontopolar region than the controls during both the tests. However, the areas in which reduced activations were demonstrated in the patients differed remarkably between the idea and letter fluency tests: reduced activations were observed in the ventral region during the former test and in the dorsal region of the frontopolar cortex during the latter test. The reduced activations in each sub-region appeared to affect the related cognitive impairment, since the patients showed significant poorer performances than the controls on both the tests. Moreover, hypoactivity during idea fluency was significantly correlated with poor social functioning as assessed using the Global Assessment of Functioning (GAF) in the patient group. The results of the present study suggest that the ventral region within the frontopolar cortex is responsible for divergent thinking, which is associated with poor social functioning in patients with schizophrenia.
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PMID:Reduced prefrontal cortex activation during divergent thinking in schizophrenia: a multi-channel NIRS study. 2067 84

We investigated the influence of the severity of schizophrenia on diabetes self-care and glycemic control among outpatients with schizophrenia and diabetes. We conducted interviews with 38 participants and reviewed their clinical charts. The mean hemoglobin A1c (HbA1c) level in the full study population was 7.65%. There was no difference in the HbA1c level between two groups of subjects classified by the severity of schizophrenia. Some diabetes self-care indicators were significantly lower in patients with high Brief Psychiatric Rating Scale scores (P < .05). Although psychotic symptoms do not appear to affect glycemic control, psychotic symptoms might affect diabetes self-care behaviors in people with schizophrenia.
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PMID:Factors associated with glycemic control and diabetes self-care among outpatients with schizophrenia and type 2 diabetes. 2125 3

Antipsychotic medications are associated with an increased risk of diabetes. Previous studies have also found an increased risk of type 2 diabetes mellitus in the relatives of schizophrenia probands. The aim of this study was to explore the metabolic adverse effects of olanzapine in a cohort of patients with newly diagnosed psychosis and minimal or no exposure to antipsychotics. Patients with newly diagnosed psychosis (n = 30) were enrolled in a 16-week open trial of olanzapine. Body mass index, fasting glucose, hemoglobin A1c, fasting insulin, IL-6, and a fasting lipid profile were measured at baseline and at 4-week intervals. There was a significant, linear increase over time in fasting glucose (P = 0.043), weight (P < 0.001), body mass index (P < 0.001), total cholesterol (P = 0.005), triglycerides (P = 0.003), and low-density lipoprotein (P = 0.013), but not hemoglobin A1c (P = 0.691), fasting insulin (P = 0.690), IL-6 (P = 0.877), or high-density lipoprotein (P = 0.446). An abnormal baseline IL-6 was a significant predictor of a greater increase in both total cholesterol (P < 0.01) and low-density lipoprotein (P < 0.01). Otherwise, neither parental history of type 2 diabetes mellitus nor baseline IL-6 predicted changes in metabolic measures. Changes in metabolic measures with olanzapine treatment can be detected early in the treatment of patients who are previously antipsychotic naive. The absence of a change in fasting insulin suggests a failure of pancreatic islet cells to compensate for the increase in fasting glucose.
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PMID:Metabolic effects of olanzapine in patients with newly diagnosed psychosis. 2134 17

The use of atypical antipsychotics in the clinical management of schizophrenia and schizoaffective disorders has been associated with the development of insulin resistance. The present study evaluates the possible individual ameliorating effect of single daily oral treatments with 20 mg/kg/day of metformin and 0.1 mg/kg of glibenclamide in two groups of Wistar rats pretreated with 0.2 mg/kg of risperidone for 60 days. Two additional groups of rats were only treated with 0.2 mg/kg of risperidone and 10 mL/kg of distilled water, respectively, also for 60 days. Results showed that oral pre-treatment with metformin significantly attenuated increases in the weight gain pattern, fasting glucose, fasting plasma insulin, serum triglyceride and total cholesterol levels that were elevated by risperidone treatment. Metformin also significantly reduced glycosylated hemoglobin concentration, fasting insulin-glucose ratio and fasting insulin resistance index. Conversely, oral pre-treatment with glibenclamide for 60 days did not significantly reduce any of the measured parameters except for glycosylated hemoglobin concentrations. Thus, results of this study showed that 20 mg/kg of metformin effectively ameliorated the development of risperidone-induced insulin resistance and dyslipidemia which was mediated via improvement in insulin resistance. This study provides insight into the therapeutic potential of metformin in preventing risperidone-induced insulin resistance diabetes mellitus and dyslipidaemia.
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PMID:Metformin: an effective attenuator of risperidone-induced insulin resistance hyperglycemia and dyslipidemia in rats. 2161 56

Nitric oxide (NO) synthase produces NO, which serves as first and second messenger in neurons, where the protein is encoded by the NOS1 gene. A functional variable number of tandem repeats (VNTR) polymorphism in the promoter region of the alternative first exon 1f of NOS1 is associated with various functions of human behavior, for example increased impulsivity, while another, non-functional variant was linked to decreased verbal working memory and a heightened risk for schizophrenia. We therefore investigated the influence of NOS1 ex 1f-VNTR on working memory function as reflected by both behavioral measures and prefrontal oxygenation. We hypothesized that homozygous short allele carriers exhibit altered brain oxygenation in task-related areas, namely the dorsolateral and ventrolateral prefrontal cortex and the parietal cortex. To this end, 56 healthy subjects were stratified into a homozygous long allele group and a homozygous short allele group comparable for age, sex and intelligence. All subjects completed a letter n-back task (one-, two-, and three-back), while concentration changes of oxygenated (O(2)Hb) hemoglobin in the prefrontal cortex were measured with functional near-infrared spectroscopy (fNIRS). We found load-associated O(2)Hb increases in the prefrontal and parts of the parietal cortex. Significant load-associated oxygenation differences between the two genotype groups could be shown for the dorsolateral prefrontal cortex and the parietal cortex. Specifically, short allele carriers showed a significantly larger increase in oxygenation in all three n-back tasks. This suggests a potential compensatory mechanism, with task-related brain regions being more active in short allele carriers to compensate for reduced NOS1 expression.
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PMID:NOS1 ex1f-VNTR polymorphism influences prefrontal brain oxygenation during a working memory task. 2162 Sep 82

Second-generation antipsychotics (SGAs) tend to induce weight gain, dyslipidemia and diabetes mellitus. For those reasons, patients treated with SGAs should receive appropriate monitoring to avoid morbidity and mortality associated with cardiovascular disease. We conducted a one-year follow-up study using Japanese blood glucose monitoring guidance in schizophrenia patients treated with SGAs to evaluate the detection capability of the guidance in real clinical settings and to assess the importance of longitudinal monitoring. This retrospective cohort study included schizophrenia patients receiving at least one SGA, who were enrolled during June 2008-January 2009 at multiple sites and who had both baseline data and follow-up monitoring data at month 12. After one-year follow-up, the probable diabetes type (fasting blood glucose is higher than 125 mg/dL, casual blood glucose is higher than 179 mg/dL, or glycosylated hemoglobin (Hb(A1c)) is greater than 6.4%) was detected in 30 (8%) of the patients, and the pre-diabetes type (fasting blood glucose is 110-125 mg/dL, or casual blood glucose is 140-179 mg/dL, or Hb(A1c) is 6.0-6.4%) in 65 (17.4%) out of the total of 374 patients. During the follow-up period, 1.5% of patients had advanced from the normal (fasting blood glucose is less than 110 mg/dL, casual blood glucose is less than 140 mg/dL, or Hb(A1c) is less than 6.0%) to probable diabetes type and 42.4% had progressed from the pre-diabetes to probable diabetes type. Predictive factors for worsening of the diabetic state were a family history of diabetes, and high serum total-cholesterol and triglyceride levels at baseline. Not only cross-sectional baseline screening but also longitudinal follow-up screening is important to detect glucose abnormalities in patients treated with SGAs.
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PMID:Screening for diabetes using monitoring guidance in schizophrenia patients treated with second-generation antipsychotics: a 1-year follow-up study. 2180 61


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