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Low BDNF levels at the onset of psychosis suggest that it may contribute to the pathogenesis of schizophrenia and perhaps, could be a candidate biological marker for positive symptoms.

Our findings suggest that BDNF may be involved in the pathophysiology of schizophrenia, and its associated cognitive impairment, especially immediate memory.

Schizophrenic patients have cognitive impairments, but gender differences in these cognitive deficits have had limited study. This study assessed cognitive functioning in 471 subjects including 122 male and 78 female schizophrenic patients and 141 male and 130 female healthy controls. We found that immediate memory, language, delayed memory and total RBANS scores were significantly decreased in schizophrenia compared with healthy controls for both genders. Male patients had significant lower immediate memory, delayed memory and total RBANS scores than female patients, and healthy controls showed a similar gender difference. The RBANS showed modest correlations with PANSS scores, duration of illness and antipsychotic dose (chlorpromazine equivalents). Almost all RBANS scores in the schizophrenics and healthy controls showed significant positive correlations with education. Thus, patients of both sexes with schizophrenia experienced more deteriorated performance than healthy controls on cognitive domains of immediate memory, language and delayed memory. Furthermore, male schizophrenic patients had more serious cognitive deficits than female patients in immediate and delayed memory, but not in language, visuospatial and attention indices. AbstractSchizophrenic patients have cognitive impairments, but gender differences in these cognitive deficits have had limited study. This study assessed cognitive functioning in 471 subjects including 172 male and 78 female schizophrenic patients and 141 male and 130 female healthy controls. We found that immediate memory, language, delayed memory and total RBANS scores were significantly decreased in schizophrenia compared with healthy controls for both genders. Male patients had significant lower immediate memory, delayed memory and total RBANS scores than female patients, and healthy controls showed a similar gender difference. The RBANS showed modest correlations with PANSS scores, duration of illness and antipsychotic dose (chlorpromazine equivalents). Almost all RBANS scores in the schizophrenics and healthy controls showed significant positive correlations with education. Thus, patients of both sexes with schizophrenia experienced more deteriorated performance than healthy controls on cognitive domains of immediate memory, language and delayed memory.Furthermore, male schizophrenic patients had more serious cognitive deficits than female patients in immediate and delayed memory, but not in language, visuospatial and attention indices.

Background 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. Methods 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 (PANSS). Results 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 significant a 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. Conclusions 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.

The improvement of cognition with tropisetron appeared to be associated with normalization in P50 deficits. Thus, α7 nAChR agonists appear to be a promising therapeutic approach for the treatment of cognitive deficits that are related to abnormal P50 suppression in schizophrenia.

Several studies have linked the production of reactive oxygen species (ROS) by the NADPH oxidase to cellular growth control. In many cases, activation of the NADPH oxidase and subsequent ROS generation is required for growth factor signaling and mitogenesis in nonimmune cells. In this study, we demonstrate that the transcriptional repressor HBP1 (HMG box-containing protein 1) regulates the gene for the p47phox regulatory subunit of the NADPH oxidase. HBP1 represses growth regulatory genes (e.g., N-Myc, c-Myc, and cyclin D1) and is an inhibitor of G 1 progression. The promoter of the p47phox gene contains six tandem high-affinity HBP1 DNA-binding elements at positions ؊1243 to ؊1318 bp from the transcriptional start site which were required for repression. Furthermore, HBP1 repressed the expression of the endogenous p47phox gene through sequence-specific binding. With HBP1 expression and the subsequent reduction in p47phox gene expression, intracellular superoxide production was correspondingly reduced. Using both the wild type and a dominant-negative mutant of HBP1, we demonstrated that the repression of superoxide production through the NADPH oxidase contributed to the observed cell cycle inhibition by HBP1. Together, these results indicate that HBP1 may contribute to the regulation of NADPH oxidase-dependent superoxide production through transcriptional repression of the p47phox gene. This study defines a transcriptional mechanism for regulating intracellular ROS levels and has implications in cell cycle regulation.The production of reactive oxygen species (ROS) has various consequences, depending on the ROS concentration and the cellular environment. For example, high levels of ROS production by the NADPH oxidase complex are essential for microbial killing by phagocytic cells. In contrast, lower ROS levels that are generated by the NADPH oxidase are essential for mitogenic signaling in many cell types (e.g., see references 9 and 10). For example, both epidermal growth factor and platelet-derived growth factor require ROS for stimulated mitogenesis (reviewed in reference 26). Recent studies have highlighted a key role for ROS in modulating signaling networks through reversible cysteine oxidation and tyrosine phosphatase regulation (22, 23; reviewed in reference 37). In this paper, we provide evidence for a transcriptional mechanism for regulating intracellular ROS levels through the repression of the NADPH oxidase. Our data indicate that the transcriptional repressor and G 1 inhibitor HBP1 (HMG box-containing protein 1) (e.g., see references 28, 29, and 32) represses the gene for the p47phox regulatory subunit of the NADPH oxidase. This mechanism has functional consequences for intracellular ROS homeostasis and growth regulation.HBP1 is a transcriptional repressor and a member of the sequence-specific HMG box family of transcription factors (reviewed in reference 38). We and others originally isolated HBP1 as a binding partner of the retinoblastoma tumor suppressor and its family member p130 (13,32). With the ...

Chronic schizophrenia patients have notable gender differences in the age at onset, smoking, symptom severity, and cognitive function favoring women, but first-episode schizophrenia patients show few gender differences.