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No large-scale genome-wide association studies (GWASs) of psychosis have been conducted in Mexico or Latin America to date. Schizophrenia and bipolar disorder in particular have been found to be highly heritable and genetically influenced. However, understanding of the biological basis of psychosis in Latin American populations is limited as previous genomic studies have almost exclusively relied on participants of Northern European ancestry. With the goal of expanding knowledge on the genomic basis of psychotic disorders within the Mexican population, the National Institute of Psychiatry Ramón de la Fuente Muñiz (INPRFM), the Harvard T.H. Chan School of Public Health, and the Broad Institute’s Stanley Center for Psychiatric Research launched the Neuropsychiatric Genetics Research of Psychosis in Mexican Populations (NeuroMex) project to collect and analyze case-control psychosis samples from 5 states across Mexico. This article describes the planned sample collection and GWAS protocol for the NeuroMex study. The 4-year study will span from April 2018 to 2022 and aims to recruit 9,208 participants: 4,604 cases and 4,604 controls. Study sites across Mexico were selected to ensure collected samples capture the genomic diversity within the Mexican population. Blood samples and phenotypic data will be collected during the participant interview process and will contribute to the development of a local biobank in Mexico. DNA extraction will be done locally and genetic analysis will take place at the Broad Institute in Cambridge, MA. We will collect extensive phenotypic information using several clinical scales. All study materials including phenotypic instruments utilized are openly available in Spanish and English. The described study represents a long-term collaboration of a number of institutions from across Mexico and the Boston area, including clinical psychiatrists, clinical researchers, computational biologists, and managers at the 3 collaborating institutions. The development of relevant data management, quality assurance, and analysis plans are the primary considerations in this protocol article. Extensive management and analysis processes were developed for both the phenotypic and genetic data collected. Capacity building, partnerships, and training between and among the collaborating institutions are intrinsic components to this study and its long-term success.

Evidence suggests that schizophrenia (SCZ), schizoaffective disorder (SAD) and bipolar disorder (BPD) share genetic risk variants. ZNF804A gene has been associated with these disorders in different populations. GWAS and candidate gene studies have reported association between the rs1344706 A allele with SCZ, SAD and BPD in European and Asian populations. In Mexican patients, no studies have specifically analyzed ZNF804A gene variants with these disorders. The aim of the study was to analyze the rs1344706 and identify common and rare variants in a targeted region of the ZNF804A gene in Mexican patients with SCZ, BPD and SAD compared with a control group.We genotyped the rs1344706 in 228 Mexican patients diagnosed with SCZ, SAD and BPD, and 295 controls. Also, an additional sample of 167 patients with these disorders and 170 controls was analyzed to identify rare and common variants using the Sanger-sequence analysis of a targeted region of ZNF804A gene.Association analysis of rs1344706 observed a higher frequency of A allele in the patients compared with the control group; however, did not show statistical differences after Bonferronís correction (χ2 = 5.3, p = 0.0208). In the sequence analysis, we did not identify rare variants; however, we identified three common variants: rs3046266, rs1366842 and rs12477430. A comparison of the three identified variants between patients and controls did not show statistical differences (p 0.0125). Finally, haplotype analysis did not show statistical differences between SCZ, SAD and BPD and controls.Our findings did not support the evidence suggesting that ZNF804A gene participates in the etiology of SCZ, SAD and BPD. Future studies are needed in a larger sample size to identify the effect of this gene in psychiatric disorders.

Background: Evidence suggests that Schizophrenia (SCZ), Schizoaffective Disorder (SAD) and Bipolar Disorder (BPD) share genetic risk variants. ZNF804A gene has been associated with these disorders in different populations. The aim was to analyze the rs1344706 SNP and identify common and rare variants in a targeted region of the ZNF804A gene in SCZ, BPD and SAD Mexican patients compared with a control group.Methods: We genotyped the rs1344706 in 228 Mexican patients diagnosed with SCZ, SAD and BPD, and 295 controls. An additional sample of 167 patients and 170 controls was analyzed to identify rare and common variants using the Sanger-sequence analysis of a targeted region of ZNF804A gene. Results: We replicated the association between the rs1344706 and SCZ, SAD and BPD. In the sequence analysis, we did not identify rare variants; however, we identified three common variants: rs3046266, rs1366842 and rs12477430. A comparison of the three identified variants between SCZ, SAD and BPD did not show statistical differences. Conclusions: Our findings support the evidence suggesting that ZNF804A gene is involved in the etiology of SZC, SAD and BPD. Future studies are needed to identify the pleiotropic effect of this gene in psychiatric disorders.

Introduction: Schizoaffective disorder (SA) is classified into bipolar (bSA) and depressive (dSA) subtypes. Although clinical differences between both have been reported, there is no clear information regarding their specific cognitive profile. Objective: To compare neurocognition between SA subtypes and schizophrenia (SC). Methods: A total of 61 patients were assessed and divided into 3 groups: 35 SC, 16 bSA, and 10 dSA. All participants signed an informed consent letter. The MATRICS Consensus Cognitive Battery, Central and South American version was used to assess neurocognition. The study was performed at the Instituto Nacional de Psiquiatría “Ramón de la Fuente”. Participants were identified by specialized psychiatrists. Trained neuropsychologists carried out the clinical and cognitive assessment, which lasted 2 h approximately. Results: The cognitive assessment showed a significant difference in Trail Making Test part A subtest (F[2,58] = 4.043; p = 0.023]. Post hoc analyses indicated that dSA obtained a significantly higher score than SC (MD = –11.523; p = 0.018). The f test showed a large effect size (f = 0.401). No statistical differences were observed regarding other cognitive variables. Conclusions: The cognitive profile of SA subtypes and SC is similar since no differences were found in most subtests. However, dSA may be less impaired than SC in measures of processing speed. Further research with larger samples must be conducted.