Suicidal attempt among patients with schizophrenia: A cross-sectional study from Morocco

Suicide constitutes the greatest risk factor for mortality in individuals with schizophrenia. Although numerous risk factors have been suggested as important predictors of suicidality in schizophrenia, most studies have focused on Caucasian and Chinese patients. This study aimed to examine the prevalence of suicide attempts in schizophrenia patients in Rabat-Sale-Kenitra, Morocco, and to identify associated clinical and sociodemographic characteristics. A cross-sectional study was conducted at the Ar-RAZI Psychiatric Center of Ibn Sina Hospital in Rabat. We examined 175 Moroccan schizophrenic patients. The sociodemographic and clinical variables were analyzed based on the presence or absence of suicide attempts. The prevalence of suicide attempts among patients was 32%. 43% of them had reported multiple suicide attempts. The majority of those who attempted suicide were single, younger, and with a lower economic status. Visual hallucinations were significantly prevalent among attempter patients compared to non-attempters (p =0.032). Consequently, visual hallucinations could be a risk factor for suicide attempts in the Moroccan population. Understanding sociodemographic and clinical characteristics associated with suicide attempts can help identify patients at higher risk and provide appropriate support and interventions to prevent suicide among the Moroccan population

The HLA-B*57:01 allele corresponds to a very large MHC haploblock likely explaining its massive effect for HIV-1 elite control

IntroductionWe have reanalyzed the genomic data of the International Collaboration for the Genomics of HIV (ICGH), centering on HIV-1 Elite Controllers.MethodsWe performed a genome-wide Association Study comparing 543 HIV Elite Controllers with 3,272 uninfected controls of European descent. Using the latest database for imputation, we analyzed 35,552 Single Nucleotide Polymorphisms (SNPs) within the Major Histocompatibility Complex (MHC) region.ResultsOur analysis identified 2,626 SNPs significantly associated (p<5. 10-8) with elite control of HIV-1 infection, including well-established MHC signals such as the rs2395029-G allele which tags HLA-B*57:01. A thorough investigation of SNPs in linkage disequilibrium with rs2395029 revealed an extensive haploblock spanning 1.9 megabases in the MHC region tagging HLA-B*57:01, comprising 379 SNP alleles impacting 72 genes. This haploblock contains damaging variations in proteins like NOTCH4 and DXO and is also associated with a strong differential pattern of expression of multiple MHC genes such as HLA-B, MICB, and ZBTB12. The study was expanded to include two cohorts of seropositive African-American individuals, where a haploblock tagging the HLA-B*57:03 allele was similarly associated with control of viral load. The mRNA expression profile of this haploblock in African Americans closely mirrored that in the European cohort.DiscussionThese findings suggest that additional molecular mechanisms beyond the conventional antigen-presenting role of class I HLA molecules may contribute to the observed influence of HLA-B*57:01/B*57:03 alleles on HIV-1 elite control. Overall, this study has uncovered a large haploblock associated with HLA-B*57 alleles, providing novel insights into their massive effect on HIV-1 elite control

Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.: HERV-W in schizophrenia and bipolar disorder

International audienceEpidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P<10-4) and in SZ (P=0.012) as compared with HC, but with higher values in BD than in SZ group (P<0.01). The corresponding DNA copy number was paradoxically lower in the genome of patients with BD (P=0.0016) or SZ (P<0.0003) than in HC. Differences in nucleotide sequence of HERV-W env were found between patients with SZ and BD as compared with HC, as well as between SZ and BD. The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ. The seroprevalence for Toxoplasma gondii yielded low but significant association with HERV-W transcriptional level in a subgroup of BD and SZ, suggesting a potential role in particular patients. A global hypothesis of mechanisms inducing such major psychoses is discussed, placing HERV-W at the crossroads between environmental, genetic and immunological factors. Thus, particular infections would act as activators of HERV-W elements in earliest life, resulting in the production of an HERV-W envelope protein, which then stimulates pro-inflammatory and neurotoxic cascades. This hypothesis needs to be further explored as it may yield major changes in our understanding and treatment of severe psychotic disorders

Schizophrenia Bulletin Open

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte

HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10-3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response

Immunity and Gilles de la Tourette syndrome: A systematic review and meta-analysis of evidence for immune implications in Tourette syndrome

Background and purpose: The neurobiology of Gilles de la Tourette syndrome (GTS) is known to involve corticostriatal loops possibly under genetic control. Less is known about possible environmental triggers of GTS. Specifically, immune-related events following possible environmental inducers have been evoked, but important controversies still exist. In this systematic review and meta-analysis, we looked for evidence in favor of such possibilities. Methods: We performed a systematic review and meta-analysis of all immunological data in PubMed. Results: We found large discrepancies concerning immune dysfunctions in GTS, and meta-analyzing cytokines data did not allow us to conclude there is an involvement of specific cytokines in GTS neurobiology. When looking specifically at pediatric autoimmune neuropsychiatric disorder associated with streptococcus/pediatric acute onset neuropsychiatric syndrome, we found some important evidence of a possible infectious involvement but in a limited number of studies. Our meta-analysis found an increased level of anti-streptolysin O antibodies in GTS patients, but the level of anti-DNase B antibodies was not increased. Conclusions: Too many questions still exist to allow us to definitively reach the conclusion that there is an infectious and immunological etiology in GTS. Much work is still needed to elucidate the possible role of immunology in GTS neurobiology and to favor immunological treatment rather than classical treatment.</p