Why sex differences in schizophrenia?
Ontology highlight
ABSTRACT:
SUBMITTER: Li R
PROVIDER: S-EPMC5688947 | biostudies-literature | 2016 Sep
REPOSITORIES: biostudies-literature
Publications
Why sex differences in schizophrenia?
Li Rena R Ma Xin X Wang Gang G Yang Jian J Wang Chuanyue C
Journal of translational neuroscience 20160901 1
Clinical observation shows that men and women are different in prevalence, symptoms, and responses to treatment of several psychiatric disorders, including schizophrenia. While the etiology of gender differences in schizophrenia is only partially understood, recent genetic studies suggest significant sex-specific pathways in the schizophrenia between men and women. More research is needed to understand the causal roles of sex differences in schizophrenia in order to ultimately develop sex-specif ...[more]
Similar Datasets
Project description:Schizophrenia is a severe psychiatric disorder which influences around 1% of the worldwide population. Differences between male and female patients with schizophrenia have been noted. There is an earlier age of onset in males compared with females with this diagnosis, and in addition, there are differences in symptom profiles between the sexes. The underlying molecular mechanism of sex difference remains unclear. Here we present a comprehensive analysis to reveal the sex differences in gene expression in schizophrenia with stringent statistics criteria. We compiled a data set consisting of 89 male controls, 90 male schizophrenia patients, 35 female controls and 32 female schizophrenia patients from six independent studies of the prefrontal cortex (PFC) in postmortem brain. When we tested for a sex by diagnosis interaction on gene expression, 23 genes were up-regulated and 23 genes were down-regulated in the male group (q-value?<?0.05), several genes are related to energy metabolism, while 4 genes are located on sex chromosome. No genes were statistically significant in the female group when multiple testing correction were conducted (q-value <0.05), most likely due to the small sample size. Our protocol and results from the male group provide a starting point for identifying the underlying different mechanism between male and female schizophrenia patients.
| S-EPMC4895727 | biostudies-literature
Project description:Patients with schizophrenia (SZ) display moderate reductions in brainstem volumes, including the midbrain, pons, superior cerebellar peduncle, and medulla oblongata. Here, we investigated alterations in brainstem volumes between SZ patients and healthy controls (HCs) stratified by sex. T1-weighted MRI brain scans were processed with FreeSurfer v6.0 in 156 SZ patients (61 males/95 females) and 205 HCs (133/72). Of the brainstem structures, pons volumes were significantly reduced, particularly in male SZ patients. The decreased pons volumes were correlated with lower levels of education but not duration of illness in male patients. These findings suggest that the reduction in pons volume in male patients might be occurred before or around the onset of the disorder.
| S-EPMC10024760 | biostudies-literature
Project description:ObjectivesPersons with schizophrenia, and women in particular, are at high risk for sleep disturbances and inflammatory activation. The sleep-inflammation link has been reported to be stronger in women within the general population. This study sought to examine the sleep-inflammation link in persons with schizophrenia and its relationship with demographic, clinical and cognitive variables.DesignCross-sectional case-control study.ParticipantsCommunity-dwelling outpatients with schizophrenia (N=144, 46% women) and non-psychiatric comparison (NC) participants (N=134, 52% women), age 26-65 years.MeasurementsReported sleep disturbances (sleep quality and duration), and mental and physical health were assessed. Cognitive assessments included executive functioning (Delis-Kaplan Executive Function System) and global cognitive functioning (Telephone Interview for Cognitive Status - modified.) Inflammatory biomarkers included pro-inflammatory cytokines [high sensitivity C-Reactive Protein (hs-CRP), Interleukin (IL)-6, Tumor Necrosis Factor-α (TNF-α)] and an anti-inflammatory cytokine (IL-10).ResultsThe schizophrenia group had longer sleep duration, worse sleep quality, and increased levels of hs-CRP, IL-6, and TNF-α compared to NCs. Women with schizophrenia were less likely to have good sleep quality and had elevated levels of hs-CRP and IL-6 compared to men with schizophrenia. In the schizophrenia group, worse sleep quality and global cognitive functioning were associated with higher hs-CRP and IL-6 levels. Female sex and younger age were also associated with higher hs-CRP levels.ConclusionsSleep disturbances and increased inflammation, which were common in schizophrenia, were associated in persons with schizophrenia. Moreover, women with schizophrenia had worse sleep quality and inflammation than men. Further examination of the sleep-inflammation links, their contribution to clinical outcomes, and sex-specific factors is warranted.
| S-EPMC6489497 | biostudies-literature
Project description:The adverse metabolic risks associated with second generation antipsychotics (SGAs) are well known, and likely contribute to the high rate of premature mortality due to cardiovascular disease in schizophrenia. Female schizophrenia patients appear to be diagnosed with metabolic diseases at higher rates than males, which may reflect disparate adverse responses to SGAs. However, the relationship between sex, metabolic risk, and drug use is less developed. We aimed to explore this relationship further by identifying rates of metabolic disease in community dwelling schizophrenia patients by sex and SGA risk. Schizophrenia participants (N = 287, 40.4% female) were included in this analysis. Oneway-ANOVA and Fisher's Exact Test were used to compare groups, as appropriate, and Cohen's d was employed to estimate the effect size of sex. In the group as a whole, the rate of metabolic syndrome was higher than previously reported, but did not differ by sex. For females, greater metabolic disturbances across all medication risk groups were seen in BMI and waist circumference (p < 0.005) but most commonly in those receiving high risk medication (clozapine or olanzapine). Additionally, the number of participants receiving medications for these metabolic disturbances was extremely low (<30%). These results suggest that female schizophrenia patients taking clozapine or olanzapine represent a group at uniquely high risk for metabolic dysfunction and future adverse cardiovascular outcomes, and warrant close monitoring by clinicians to prevent worsening of metabolic risk through proper monitoring and interventions.
| S-EPMC5472174 | biostudies-literature
Project description:BackgroundWhile schizophrenia differs between males and females in the age of onset, symptomatology, and disease course, the molecular mechanisms underlying these differences remain uncharacterized.MethodsTo address questions about the sex-specific effects of schizophrenia, we performed a large-scale transcriptome analysis of RNA sequencing data from 437 controls and 341 cases from two distinct cohorts from the CommonMind Consortium.ResultsAnalysis across the cohorts identified a reproducible gene expression signature of schizophrenia that was highly concordant with previous work. Differential expression across sex was reproducible across cohorts and identified X- and Y-linked genes, as well as those involved in dosage compensation. Intriguingly, the sex expression signature was also enriched for genes involved in neurexin family protein binding and synaptic organization. Differential expression analysis testing a sex-by-diagnosis interaction effect did not identify any genome-wide signature after multiple testing corrections. Gene coexpression network analysis was performed to reduce dimensionality from thousands of genes to dozens of modules and elucidate interactions among genes. We found enrichment of coexpression modules for sex-by-diagnosis differential expression signatures, which were highly reproducible across the two cohorts and involved a number of diverse pathways, including neural nucleus development, neuron projection morphogenesis, and regulation of neural precursor cell proliferation.ConclusionsOverall, our results indicate that the effect size of sex differences in schizophrenia gene expression signatures is small and underscore the challenge of identifying robust sex-by-diagnosis signatures, which will require future analyses in larger cohorts.
| S-EPMC8463632 | biostudies-literature
Project description:BackgroundCognitive deficits are common in patients with schizophrenia (SCZ). Abnormal serum total bilirubin (TBIL) levels have been involved in cognitive deficits associated with neuropsychiatric diseases such as mild cognitive impairment and subcortical ischemic vascular disease. However, this relationship has not yet been fully investigated in patients with SCZ. Therefore, the aim of this study was to investigate the association between the serum TBIL concentration and cognitive deficits in SCZ patients and to determine whether a sex difference exists in the association.MethodsA total of 455 participants were eligible and included in this cross-sectional study. Cognition was evaluated using the Montreal Cognitive Assessment. Serum TBIL concentration was measured with an automatic biochemistry analyzer according to the routine protocol in the hospital medical laboratory.ResultsSerum TBIL levels were lower in the cognition impairment group than in the cognition normal group in male patients. In contrast, serum TBIL levels tended to be increased in the cognition impairment group in female patients, although the difference was not significant. Further stepwise multiple regression analysis stratified by sex showed that serum TBIL was independently and positively associated with cognitive function in male patients but not in female patients. Moreover, the association between serum TBIL level and cognitive function was also identified by the propensity score matching (PSM) method in male patients, but not in female patients.ConclusionThese findings suggest that lower serum TBIL levels may be associated with cognitive impairment in male SCZ patients.
| S-EPMC8353745 | biostudies-literature
Project description:Although previous findings identified an association between C-reactive protein (CRP) levels, and impaired cognitive functions in patients with schizophrenia (SZ), little is currently known about the relationship between inflammation, cognition, and sex in SZ. The current study aimed to explore the association between peripheral inflammation and cognitive impairment in SZ as a function of sex. The sample included 132 clinically stable patients with SZ, of whom 82 were males (62.1%) and 50 females (37.9%). Sociodemographic data were collected, an accurate assessment was performed using the Positive and Negative Syndrome (PANSS), Clinical Assessment Interview for Negative Symptoms (CAINS), and Calgary Depression (CDS) scales, and the MATRICS Consensus Cognitive Battery (MCCB), and CRP levels were tested. A Pearson correlation and multiple regression analyses, including potential confounding factors, were performed. We found an inverse association between CRP levels and performance on visual learning (r?=?? 0.386, p?=?0.006) domain in female patients only, whereas no correlations were found in males. The regression model for women retained age (??=?? 0.319, p?=?0.017), the CAINS-MAP score (??=?? 0.247, p?=?0.070), and the CRP (??=?? 0.321, p?=?0.013) as predictors of visual learning. Our results suggest the possible existence of sex-specific modulation of the association between systemic inflammation and the cognitive features of the illness.
| S-EPMC7524709 | biostudies-literature
Project description:There are studies showing that gene polymorphisms within the transforming growth factor-? (TGF-?) signaling constitute schizophrenia risk variants. However, the association between TGFB1 gene polymorphisms (+869T/C and +915G/C), TGF-? level with schizophrenia course, and its symptomatology together with cognitive functioning has not been investigated so far. We included 151 patients with schizophrenia and 279 healthy controls. Cognitive functioning was assessed using Rey Auditory Verbal Learning Test, Trail Making Test (TMT)-A and TMT-B, Verbal Fluency task, Stroop test, as well as selected subtests from the Wechsler Adults Intelligence Scale - Revised, Polish adaptation (WAIS-R-Pl): Digit Symbol Coding, Digit Span Forward and Backward, and Similarities. Additionally, serum TGF-? levels were measured in 88 schizophrenia patients and 88 healthy controls. Serum TGF-? level was significantly higher among patients with schizophrenia in comparison with healthy controls; however, the studied polymorphisms were not associated with TGF-? level in schizophrenia patients. Subjects carrying the +869T allele performed significantly worse in comparison with +869CC homozygotes on Stroop task, Verbal Fluency task and Digit Symbol Coding task. There was a significant difference in age of psychosis onset in female schizophrenia patients with respect to the TGFB1 +869T/C polymorphism. Additionally, adjustment for possible confounders revealed that there was a significant difference in cognitive performance on Digit Symbol Coding task with respect to the TGFB1 +869T/C polymorphism among female schizophrenia patients. Our results suggest that TGF-? signaling might be a valid link contributing to observed differences in age of onset and the level of cognitive decline between male and female schizophrenia patients.
| S-EPMC4356692 | biostudies-literature
Project description:The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.
| S-EPMC5696105 | biostudies-literature
Project description:Schizophrenia (SZ) is a serious mental disorder that is typically treated with antipsychotic medication. Treatment-resistant schizophrenia (TRS) is the condition where symptoms remain after pharmacological intervention, resulting in long-lasting functional and social impairments. As the identification and treatment of a TRS patient requires previous failed treatments, early mechanisms of detection are needed in order to quicken the access to effective therapy, as well as improve treatment adherence. In this study, we aim to find a microRNA (miRNA) signature for TRS, as well as to shed some light on the molecular pathways potentially involved in this severe condition. To do this, we compared the blood miRNAs of schizophrenia patients that respond to medication and TRS patients, thus obtaining a 16-miRNA TRS profile. Then, we assessed the ability of this signature to separate responders and TRS patients using hierarchical clustering, observing that most of them are grouped correctly (~70% accuracy). We also conducted a network, pathway analysis, and bibliography search to spot molecular pathways potentially altered in TRS. We found that the response to stress seems to be a key factor in TRS and that proteins p53, SIRT1, MDM2, and TRIM28 could be the potential mediators of such responses. Finally, we suggest a molecular pathway potentially regulated by the miRNAs of the TRS profile.
2023-01-18 | GSE223043 | GEO