FOXP2 contributes to the cognitive impairment in chronic patients with schizophrenia.
ABSTRACT: The forkhead-box P2 (FOXP2), involving in language and memory function, has been identified as susceptibility to schizophrenia. However, no study examined the role of FOXP2 on cognitive impairment in schizophrenia. Total 1106 inpatients with schizophrenia and 404 controls were recruited and genotyped. Among them, 867 patients and 402 controls were assessed through the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). SHEsis software was used to investigate the association of FOXP2 rs10447760 with schizophrenia, followed by logistic regression. The model of covariance (ANCOVA) and multivariate analysis were conducted to investigate the effect of FOXP2 rs10447760 on cognitive impairment in schizophrenia. No differences in the genotypic and allelic frequencies of the FOXP2 rs10447760 were found between patients and controls (both p> 0.05). Except for the visuospatial/constructional score (p > 0.05), other five RBANS scores were lower in patients compared to controls (all p < 0.0001). Interestingly, we found immediate memory score was lower in patients carrying genotype CT compared to genotype CC (F=5.19, p=0.02), adjusting for confounding data. Our study suggested that FOXP2 rs10447760 has no effect on the susceptibility to schizophrenia, while it may be associated with its cognitive impairment, especially immediate memory in chronic schizophrenia.
Project description:Schizophrenic patients have higher smoking rates than the general population. Studies show that smoking may be a form of self-medication in an attempt to alleviate cognitive deficits in schizophrenic patients of European background. This study examined the relationships between smoking and cognitive deficits in Chinese schizophrenic patients, which have previously received little systemic study. We recruited 580 male chronic patients meeting DSM-IV criteria for schizophrenia and 175 male control subjects who were matched on age and education. The subjects completed a detailed cigarette smoking questionnaire, the Fagerstrom Test for Nicotine Dependence (FTND), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients also were rated on the Positive and Negative Symptom Scale (PANSS), the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES), and the Abnormal Involuntary Movement Scale (AIMS). All five RBANS subscales except for the Visuospatial/Constructional index showed significantly lower cognitive performance for schizophrenics than normal controls. The schizophrenic smokers scored lower than the schizophrenic non-smokers on the RBANS total score and the Visuospatial/Constructional and Immediate Memory indices. Similarly, the control smokers scored lower than the control non-smokers on the RBANS total score and the Immediate Memory index . Also, the schizophrenic smokers consistently performed the poorest on the cognitive domains of the RBANS. Among the schizophrenic patients, smokers displayed significantly fewer negative symptoms than non-smokers. Using multivariate regression analysis the following variables were independently associated with the RBANS total score: years of education, PANSS negative symptom score, age at schizophrenia onset, and number of hospitalizations. Our results show that smoking is associated with significant cognitive impairment in both schizophrenic patients and normal controls, but the smokers with schizophrenia had a reduced level of negative symptoms, suggesting that the benefits of smoking for those with schizophrenia may be limited to certain aspects of a given clinical phenotype.
Project description:Studies suggest that a functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) may mediate hippocampal-dependent cognitive functions. A few studies have reported its role in cognitive deficits in schizophrenia including its association with peripheral BDNF levels as a mediator of these cognitive deficits. We assessed 657 schizophrenic inpatients and 445 healthy controls on the repeatable battery for the assessment of neuropsychological status (RBANS), the presence of the BDNF Val66Met polymorphism and serum BDNF levels. We assessed patient psychopathology using the Positive and Negative Syndrome Scale. We showed that visuospatial/constructional abilities significantly differed by genotype but not genotype × diagnosis, and the Val allele was associated with better visuospatial/constructional performance in both schizophrenic patients and healthy controls. Attention performance showed a significant genotype by diagnosis effect. Met allele-associated attention impairment was specific to schizophrenic patients and not shown in healthy controls. In the patient group, partial correlation analysis showed a significant positive correlation between serum BDNF and the RBANS total score. Furthermore, the RBANS total score showed a statistically significant BDNF level × genotype interaction. We demonstrated an association between the BDNF Met variant and poor visuospatial/constructional performance. Furthermore, the BDNF Met variant may be specific to attentional decrements in schizophrenic patients. The association between decreased BDNF serum levels and cognitive impairment in schizophrenia is dependent on the BDNF Val66Met polymorphism.
Project description:Type 2 diabetes (T2DM) is associated with cognitive deficits. However, their pathophysiological mechanisms are still unknown. Recent study suggests that brain-derived neurotrophic factor (BDNF) is correlated with cognitive deficits in T2DM patients. This study was to determine whether altered serum BDNF levels and cognitive deficits depended on the BDNF Val66Met polymorphism in T2DM.The BDNF Val66Met polymorphism may not contribute directly to the susceptibility to T2DM. The total and nearly all index scores (all p < 0.01) except for the attention and visuospatial/constructional indexes (both p > 0.05) of RBANS were markedly decreased in T2DM compared with healthy controls. Serum BDNF levels were significantly lower in patients than that in controls (p < 0.001), and BDNF was positively associated with delayed memory in patients (p < 0.05). The Met variant was associated with worse delayed memory performance among T2DM patients but not among normal controls. Moreover, serum BDNF was positively associated with delayed memory among Met homozygote patients (? = 0.29, t = 2.21, p = 0.033), while serum BDNF was negatively associated the RBANS total score (? = -0.92, t = -3.40, p = 0.002) and language index (? = -1.17, t = -3.54, p = 0.001) among Val homozygote T2DM patients.BDNF gene Val66Met variation may be associated with cognitive deficits in T2DM, especially with delayed memory. The association between lower BDNF serum levels and cognitive impairment in T2DM is dependent on the BDNF Val66Met polymorphism.We recruited 311 T2DM patients and 346 healthy controls and compared them on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), serum BDNF levels, and the BDNF Val66Met polymorphism.
Project description:Cognitive dysfunction has been recognized as a cardinal feature of schizophrenia. Elucidating the neurobiological substrates of cognitive dysfunction in schizophrenia would help identify the underlying mechanism of this disorder. The rs1064395 single nucleotide polymorphism, within the gene encoding neurocan (NCAN), is reported to be associated with schizophrenia in European populations and may influence brain structure in patients with schizophrenia.In this study, we aimed to explore whether NCAN rs1064395 confers some risk for schizophrenia and cognitive dysfunction in Han Chinese. We recruited 681 patients with schizophrenia and 699 healthy subjects. Two hundred and fifty-four patients were evaluated according to Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).There were no significant differences in genotype or allele distributions of the rs1064395 polymorphism between the schizophrenia and control groups. Patients showed significantly poorer performance than controls on immediate memory, visuospatial skill, language, attention, delayed memory, and total RBANS score. Patients with the A/A or A/G genotype of rs1064395 had lower scores of immediate memory, visuospatial skill, attention, and total RBANS score than those with the G/G genotype. We performed an expression quantitative trait loci analysis and observed a significant association between rs1064395 and NCAN expression in the frontal (P=0.0022, P=0.022 after Bonferroni correction) and cerebellar cortex (P=0.0032, P=0.032 after Bonferroni correction).Our findings indicate that this single nucleotide polymorphism may be a risk factor for cognitive dysfunction in patients with schizophrenia. Further investigations are warranted for validation purposes and to identify the precise mechanism by which rs1064395 influences cognitive performance in patients with schizophrenia.
Project description:Lower extremity skeletal muscle mass (LESM) in Type 2 Diabetes (T2D) has been linked to adverse clinical events, but it is not known whether it is associated with cognitive difficulties. We conducted a cross-sectional study on 1,235 people (mean age 61.4?±?8.0 years) with T2D under primary and secondary care in Singapore. Bioelectrical impedance analyses (BIA) measures of upper extremity skeletal muscle mass (UESM), LESM and appendicular skeletal muscle index (SMI) were related to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measures of cognition, in multiple linear regression. In multivariable models, tertile 1 LESM (b?=?-2.62 (-3.92 to -1.32)) and tertile 2 LESM (b?=?-1.73 (-2.73 to -0.73)), referenced to tertile 3) were significantly associated with decreased RBANS total score. Significant associations of LESM with cognitive domain performances were observed for tertile 1 (b?=?-3.75 (-5.98 to -1.52)) and tertile 2 (b?=?-1.98 (-3.69 to -0.27)) with immediate memory, and for tertile 1 (b?=?-3.05 (-4.86 to -1.24)) and tertile 2 (b?=?-1.87 (-3.25 to -0.48)) with delayed memory, and for tertile 1 (b?=?-2.99 (-5.30 to -0.68)) with visuospatial/constructional ability. Tertile 1 SMI (b?=?-1.94 (-3.79 to -0.08) and tertile 2 SMI (b?=?-1.75 (-3.14 to -0.37)) were also associated with delayed memory. There were no associations between UESM with cognitive performance. Lower LESM may be a useful marker of possible co-occuring cognitive dysfunction.
Project description:Excessive reactive oxygen species are thought to produce oxidative damage that underlies neurodegeneration and cognitive impairment in several disorders including schizophrenia. The functional Ala-9Val polymorphism of the mitochondrial enzyme manganese superoxide dismutase (MnSOD), which detoxifies superoxide radicals to hydrogen peroxide, has been associated with schizophrenia. However, no study has reported its role in cognitive deficits of schizophrenia as mediated through MnSOD activity. We recruited 923 schizophrenic inpatients and 566 healthy controls and compared them on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), plasma MnSOD activity, and the MnSOD Ala-9Val polymorphism. We assessed patient psychopathology using the Positive and Negative Syndrome Scale. We showed that the MnSOD Ala-9Val polymorphism may not contribute directly to the susceptibility to schizophrenia. The Ala variant was associated with worse attention performance among chronic schizophrenic patients but not among normal controls. Plasma MnSOD activity was significantly decreased in patients compared with that in normal controls. Moreover, MnSOD activity among the schizophrenic Ala allele carriers was correlated with the degree of cognitive impairments, especially attention and RBANS total score. We demonstrated an association between the MnSOD Ala-9Val variant and poor attention in schizophrenia. The association between higher MnSOD activity and cognitive impairment in schizophrenia is dependent on the MnSOD Ala-9Val polymorphism.
Project description:Objective: This study aimed to investigate the association between cognitive impairment and cerebral haemodynamic changes in patients with chronic vertebra-basilar (VB) stenosis. Methods: Patients with severe posterior circulation VB stenosis and infarction or a history of infarction for more than 2 weeks from January 2014 to January 2015 were enrolled (n = 96). They were divided into three groups, namely, the computed tomography perfusion (CTP) normal group, the CTP compensated group, and the CTP decompensated group. Cognitive function was assessed using a validated Chinese version of the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Regression models were used to identify independent risk factors for cognitive impairment. Results: The MMSE and FAB scores of patients in the CTP decompensated group were significantly lower than those of patients in the CTP normal and CTP compensated groups (all p < 0.05). The RBANS total and its domain scores, including immediate memory, visual acuity, and delayed memory, in the CTP compensated and CTP decompensated groups were significantly lower than those in the CTP normal group (all p < 0.05). Multiple regression analyses showed that CTP compensation, CTP decompensation, severe VB tandem stenosis, and multiple infarctions were independent risk factors for cognitive impairment. Conclusions: Low perfusion caused by severe VB stenosis can lead to extensive cognitive impairments in areas such as immediate memory, visual span, and delayed memory.
Project description:After recovery from an acute episode of acquired thrombotic thrombocytopenic purpura (TTP), patients often describe problems with memory, concentration, and endurance. We have previously reported the occurrence of depression and cognitive impairment in these patients. In this study, we describe the frequency, severity, and clinical course of depression and cognitive impairment. Fifty-two (85%) out of 61 eligible Oklahoma Registry patients who had recovered from TTP, documented by ADAMTS13 activity <10%, have had at least one (median, four) evaluation for depression over 11 years using the Beck Depression Inventory-II; 31 (59%) patients screened positive for depression at least once; in 15 (29%), the results suggested severe depression at least once. Nine of these 15 patients had a psychiatric interview, the definitive diagnostic evaluation; the diagnosis of major depressive disorder was established in eight (89%) patients. In 2014, cognitive ability was evaluated in 33 patients by the Montreal Cognitive Assessment and the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Both tests detected significant cognitive impairment in the patients as a group. Fifteen out of the 33 patients had been evaluated by extensive cognitive tests in 2006. The 2014 RBANS results were significantly worse than the 2006 results for the overall score and two out of the five RBANS domains (immediate and delayed memory). Neither depression nor cognitive impairment was significantly associated with the occurrence of relapses or ADAMTS13 activity <10% during remission. These observations emphasize the importance of screening evaluations for depression and cognitive impairment after recovery from acquired TTP.
Project description:Recent studies demonstrate that brain-derived neurotrophic factor (BDNF) might be associated with nicotine addiction, and circulating BDNF is a biomarker of memory and general cognitive function. Moreover, studies suggest that a functional polymorphism of the BDNF Val66Met may mediate hippocampal-dependent cognitive functions. We aimed to explore the relationships between smoking, cognitive performance and BDNF in a normal Chinese Han population. We recruited 628 male healthy subjects, inducing 322 smokers and 306 nonsmokers, and genotyped them the BDNF Val66Met polymorphism. Of these, we assessed 114 smokers and 98 nonsmokers on the repeatable battery for the assessment of neuropsychological status (RBANS), and 103 smokers and 89 nonsmokers on serum BDNF levels. Smokers scored lower than the nonsmokers on RBANS total score (p?=?0.002), immediate memory (p?=?0.003) and delayed memory (p?=?0.021). BDNF levels among the smokers who were Val allele carriers were correlated with the degree of cognitive impairments, especially attention, as well as with the carbon monoxide concentrations. Our findings suggest that smoking is associated with cognitive impairment in a male Chinese Han population. The association between higher BDNF levels and cognitive impairment, mainly attention in smokers appears to be dependent on the BDNF Val66Met polymorphism.
Project description:Background Alcohol dependence (AD) patients have a high prevalence of aggressive behavior (AB). The frontal cortex and amygdala contains various neurotransmitter systems and plays an important role in AB, which is also associated with cognitive deficits. However, to date, no study has addressed the association of metabolites in the frontal cortex and amygdala with cognitive deficits in Chinese aggressive behavior-alcohol dependent patients(AB-ADs). Methods We recruited 80 male AD and 40 male healthy controls (HCs), who completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Modified Overt Aggression Scale (MOAS), and the proton magnetic resonance spectroscopy (¹H MRS) scan using 3.0T Siemens. The ¹H MRS data were automatically fitted with a linear combination model for quantification of metabolite levels of n-acetyl-aspartate (NAA), glutamate (Glu), Choline (Cho) and creatine (Cr). Metabolite levels were reported as ratios to Cr. Results The AB-ADs group scored significantly lower than the non-aggression-alcohol dependent patients (NA-ADs) on these two RBANS subscales (immediate memory and attention function indices). The AB-ADs group showed a significant reduction in NAA/CR ratio in the left frontal cortex and Cho/Cr ratio in the left amygdala, and elevation in Glu/Cr ratio in the bilateral amygdala, compared with the NA-ADs group. The NAA/Cr ratio in the left frontal cortex was positively associated with immediate memory (r=0.60, P<0.05), and the Glu/Cr ratio in the right amygdala was negatively associated with delayed memory (r=-0.44,P<0.05) in AB-ADs group. Conclusions Metabolite alterations in the frontal cortex and amygdala may be involved in the pathophysiology of AB in AD and its associated cognitive impairment, especially immediate memory and delayed memory.