BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10-6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10-7; rs73033497, p = 8.8 × 10-7; rs7914279, p = 6.4 × 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

• Klíčová slova
• Bipolar disorder, Genome-wide association study, Genotype-by-sex interaction, Major depressive disorder, Schizophrenia, Sex differences,
• MeSH
• bipolární porucha genetika   MeSH
• celogenomová asociační studie MeSH
• depresivní porucha unipolární * genetika   MeSH
• endoteliální buňky MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• pohlavní dimorfismus * MeSH
• psychotické poruchy * genetika   MeSH
• receptory vaskulárního endoteliálního růstového faktoru MeSH
• schizofrenie genetika   MeSH
• sulfurtransferasy MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• MOCOS protein, human MeSH Prohlížeč
• receptory vaskulárního endoteliálního růstového faktoru MeSH
• sulfurtransferasy MeSH

INTRODUCTION: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. METHODS: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. RESULTS: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. DISCUSSION: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.

• Klíčová slova
• illness course, outcome, schizophrenia, staging,
• MeSH
• dospělí MeSH
• faktorová analýza statistická MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• progrese nemoci * MeSH
• psychiatrické posuzovací škály statistika a číselné údaje   MeSH
• schizofrenie klasifikace   diagnóza   patofyziologie   MeSH
• Sotosův syndrom MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Nigérie MeSH

BACKGROUND: Despite the recent increase of research interest in involuntary treatment and the use of coercive measures, gender differences among coerced schizophrenia patients still remain understudied. It is well recognized that there are gender differences both in biological correlates and clinical presentations in schizophrenia, which is one of the most common diagnoses among patients who are treated against their will. The extent to which these differences may result in a difference in the use of coercive measures for men and women during the acute phase of the disease has not been studied. METHODS: 291 male and 231 female coerced patients with schizophrenia were included in this study, which utilized data gathered by the EUNOMIA project (European Evaluation of Coercion in Psychiatry and Harmonization of Best Clinical Practice) and was carried out as a multi-centre prospective cohort study at 13 centers in 12 European countries. Sociodemographic and clinical characteristics, social functioning and aggressive behavior in patients who received any form of coercive measure (seclusion and/or forced medication and/or physical restraint) during their hospital stay were assessed. RESULTS: When compared to the non-coerced inpatient population, there was no difference in sociodemographic or clinical characteristics across either gender. However coerced female patients did show a worse social functioning than their coerced male counterparts, a finding which contrasts with the non-coerced inpatient population. Moreover, patterns of aggressive behavior were different between men and women, such that women exhibited aggressive behavior more frequently, but men committed severe aggressive acts more frequently. Staff used forced medication in women more frequently and physical restraint and seclusion more frequently with men. CONCLUSIONS: Results of this study point towards a higher threshold of aggressive behavior the treatment of women with coercive measures. This may be because less serious aggressive actions trigger the application of coercive measures in men. Moreover coerced women showed diminished social functioning, and more importantly more severe symptoms from the "excitement/hostile" cluster in contrast to coerced men. National and international recommendation on coercive treatment practices should include appropriate consideration of the evidence of gender differences in clinical presentation and aggressive behaviors found in inpatient populations.

• MeSH
• agrese psychologie   MeSH
• dospělí MeSH
• hospitalizovaní pacienti psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pohlavní dimorfismus * MeSH
• prospektivní studie MeSH
• schizofrenie (psychologie) * MeSH
• schizofrenie terapie   MeSH
• stupeň závažnosti nemoci MeSH
• ústavy pro duševně nemocné MeSH
• zodpovědnost duševně nemocného * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

There is accumulating evidence that disturbances in N-methyl-D: -aspartate receptor (NMDA-R) functioning are associated with the pathogenesis of schizophrenia. To assess actual changes in the expression of the GluN1 subunit and its isoforms, we measured absolute differences in the levels of mRNA/protein for panGluN1 (eight isoforms altogether) as well as the mRNA individual isoforms in the postmortem left/right hippocampus of patients with schizophrenia in comparison with non-psychiatric subjects. There were no significant differences in the panGluN1 subunit mRNA expression, but the absolute left/right differences were much more pronounced in the patients with schizophrenia. Protein levels of the GluN1 subunit in the left hippocampus in male schizophrenic patients were lower than controls. The expression of the NR1-4b isoform was attenuated in the left, whereas the NR1-2b was reduced in the right hippocampus of schizophrenic patients. Isoforms associated with the efficiency of NMDA-induced gene expression and with phosphorylation occurred more commonly in schizophrenic hippocampi. In summary, our study suggests that NMDA-R hypofunction in schizophrenia might be selectively dependent on the dysregulation of GluN1 subunit expression, which exhibits a somewhat different expression in the left/right hippocampus of psychotic patients.

• MeSH
• alternativní sestřih MeSH
• lidé MeSH
• messenger RNA biosyntéza   genetika   MeSH
• podjednotky proteinů biosyntéza   genetika   MeSH
• protein - isoformy biosyntéza   genetika   MeSH
• receptory N-methyl-D-aspartátu biosyntéza   genetika   MeSH
• schizofrenie metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH
• podjednotky proteinů MeSH
• protein - isoformy MeSH
• receptory N-methyl-D-aspartátu MeSH