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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.

We aimed to compare processing speed (PS) and its subcomponents in schizophrenia (SC) and schizoaffective disorder (SA). Thirty-five patients were divided into two groups (SC=18; SA=17). PS tasks from the MATRICS Consensus Cognitive Battery Central/South America version were used. Additional PS subcomponents were analyzed (i.e., behavioral execution, response processing, and accuracy). SA obtained significant higher scores than SC in response processing, verbal fluency and the PS general domain. Our results indicate that PS is a potential cognitive marker to differentiate between SC and SA. Further research with larger samples must be conducted.

Background: Facial affect recognition is the ability of all individuals to recognize basic forms of affective expression reflected on people’s faces. These expressions are happiness, sadness, fear, disgust, surprise, anger, and the absence of emotion, also called neutral expression. Patients with schizophrenia present difficulty in recognizing these expressions in themselves and/or in other people. Objective: The objective was to determinate which emotions were confused and for what other emotion they were taken for (misattribution). Method: We included three groups: 34 schizophrenic patients, 34 siblings, and 34 control subjects. All patients attend the schizophrenia clinic, their siblings were those closest in age and gender, and subjects without mental illness were paired by age and gender. We used SCID-I and SCL-90 scales to discard mental illness in siblings and controls. PANSS, CDSS, and CGI were used to measure the severity of the disease in schizophrenic patients. We used the Pictures of Facial Affect developed by Ekman (1976), to evaluate facial affect recognition. Results: Across all groups, the least recognized emotion was fear; in the patients and siblings groups, the most recognized emotion was surprise. In the patient group happiness was mistaken for the neutral face in 13%. The patients mistook anger for neutral face in 5.6%, fear in 5.2%, surprise in 5.0%, and disgust in 4.9 %. Neutral face: only the patients group mistook the neutral face for sadness in 4.6%. Fear was the least recognized emotion; the patient group mistook it for surprise in 42.6% and anger in 6.9 %. The siblings mistook it for surprise in 41.3 %, and the control group also for surprise in 25.4%. Disgust: It was mistaken for anger by patients in 25.6%, siblings in 23.3%, and control subjects in 11.5%. Sadness: it was mistaken for fear in 15.6%, and for neutral faces in 10.9% in the patients group. In the siblings group the sadness was mistaken for fear in 14.1%, and the controls group sadness was mistaken for fear in 11.1%.

Introducción. La esquizofrenia es un trastorno mental que posee múltiples dimensiones sintomáticas y las alteraciones cognitivas son características cardinales en la evolución del trastorno. El uso de clinimetría para evaluar dichas deficiencias puede aportar información en la investigación en este campo. Objetivo. Determinar la validez y confiabilidad de la Escala de Evaluación Cognitiva Montreal (MoCA) para la evaluación del déficit cognitivo en pacientes con el diagnóstico de esquizofrenia. Material y métodos. Se evaluaron cien pacientes con diagnóstico de esquizofrenia reclutados en la Clínica de Esquizofrenia del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Se aplicaron las escalas de MoCA, MMSE y PANSS para la valoración de las funciones cognitivas. Se estableció la confiabilidad del MoCA con el Alfa de Cronbach y se estableció su validez concurrente con el MMSE y la subescala cognitiva de la PANSS. Resultados. De acuerdo al MMSE (con ajuste de escolaridad) el 8% de los pacientes fueron clasificados con deterioro cognitivo en contraste con el puntaje total del MoCA que reporto 69% de la muestra con deterioro cognitivo. La escala MoCA obtuvo una confiabilidad (Alfa de Cronbach=0.71) similar a la observada por el MMSE (?=0.70) y adecuada validez concurrente. Conclusiones. La MoCA es un instrumento confiable y válido para establecer la presencia de deterioro cognitivo leve en pacientes con esquizofrenia, sencillo y de fácil aplicación en la práctica clínica psiquiátrica cotidiana.

espanolIntroduccion Diversos estudios han explorado la relacion entre los niveles de prolactina serica, la sintomatologia y la disfuncion cognitiva en individuos con alto riesgo de psicosis y pacientes con un primer episodio psicotico. Sin embargo, la relacion entre tales variables es poco comprendida en el caso de los pacientes cronicos con esquizofrenia. Objetivo Evaluar la relacion entre los niveles de prolactina, el deterioro neuropsicologico y la severidad de los sintomas en pacientes cronicos. Metodo Se evaluo un total de 31 pacientes. El rango de edad fue de 18 a 60 anos, quienes recibieron tratamiento antipsicotico durante un mes como minimo. Los datos se obtuvieron de entrevistas y de la aplicacion de la PANSS y la MCCB. La medicion de la prolactina se realizo con una muestra de 500 microlitros de suero, con una tecnica de quimioluminiscencia. Resultados La muestra estuvo compuesta en su mayoria por hombres (77.4%), con una edad media de 37.65 anos, 13.29 anos de escolaridad y una duracion de la enfermedad de 11.58 anos. No se observaron correlaciones entre los niveles de prolactina y los componentes y subescalas del PANSS. Solo en los pacientes varones se da una correlacion negativa entre los niveles de prolactina con la puntuacion global combinada de la bateria de MCCB y los dominios cognitivos de razonamiento y aprendizaje verbal. Discusion y conclusiones Los hombres diagnosticados con esquizofrenia pueden ser particularmente vulnerables a los efectos negativos de la hiperprolactinemia sobre la cognicion. Teoricamente, estos datos sugieren un efecto protector de las hormonas en las mujeres con esta enfermedad. EnglishIntroduction: several studies have explored the relationship between serum prolactin levels, symptomatology, and cognitive dysfunction in individuals at high risk for psychosis and patients with a first psychotic episode. However, the relationship between such variables is poorly understood in the case of chronic patients. Objective: to assess the relationship between prolactin levels, neuropsychological impairment, and symptom severity in patients with chronic schizophrenia. Method: a total of 31 patients with diagnosis of schizophrenia were evaluated between May and December 2018. The age range was 18 to 60 years, with patients receiving antipsychotic treatment during a month at least. Data was obtained from clinical records, interviews, clinimetry, and with the application of the PANSS and the MCCB battery. For the prolactin measurement, the analysis was performed on a sample of 500 microliters of serum, with a chemiluminescence technique. Results: the sample was comprised mostly by men (77.4%), with a mean age of 37.65 years, 13.29 years of formal education, and disease duration of 11.58 years. No correlations were observed between prolactin levels and PANSS components and subscales. Only in male patients is there a negative correlation was found between prolactin levels with the overall combined score of the MCCB battery and cognitive domains of reasoning and verbal learning. Discussion and conclusions: men diagnosed with schizophrenia may be particularly vulnerable to the negative effects of hyperprolactinemia on cognition. These preliminary data have clinical implications for close monitoring of prolactin and cognitive decline in males with schizophrenia. Theoretically, these data are suggestive of a protective effect of hormones in women with this condition.