Association of FAAH p.Pro129Thr and COMT p.Ala72Ser with schizophrenia and comorbid substance use through next-generation sequencing: an exploratory analysis

Objective: Individuals with schizophrenia and substance use disorders have a poor prognosis and increased psychiatric symptoms. The present study aimed to explore the association of 106 genes in individuals with schizophrenia and comorbid substance use through a next-generation sequencing (NGS) analysis and different in silico algorithms. Methods: We included 105 individuals diagnosed with schizophrenia and a family history of schizophrenia, of whom 49 (46.67%) presented comorbid substance use. Using NGS, we sequenced 106 genes previously associated with schizophrenia. Logistic regression models were used to assess differences in allele frequencies, and a generalized gene-set analysis was performed at the gene level. Functional annotations were performed using different algorithms and databases. Results: We identified a total of 3,109 variants, of which 25 were associated with schizophrenia and comorbid substance use and were located in regulatory and coding regions. We found low-frequency variants in COMT p.Ala72Ser, independently of p.Val158Met, that were associated with substance use. The endocannabinoid functional variant FAAH p.Pro129Thr was also associated with substance use. Conclusions: Genetic variants of genes related to dopaminergic and cannabinoid neurotransmitter systems were associated with comorbid substance use in schizophrenia. Nevertheless, more studies with larger sample sizes are needed to confirm our findings.

Riesgo de sindemia de COVID-19 y fiebre del dengue en el sur de México / Risk of a syndemic between COVID-19 and dengue fever in southern Mexico

Resumen Una sindemia es la convergencia de dos o más enfermedades en un mismo espacio y tiempo. En México, la epidemia de dengue está activa y predomina en zonas del Pacífico y Golfo de México; por su parte, la epidemia de COVID-19 afecta severamente las mismas zonas que el dengue. Dado que estas enfermedades comparten numerosas manifestaciones clínicas, en zonas endémicas de enfermedades tropicales es importante la evaluación minuciosa del paciente que consulta por fiebre, para establecer oportunamente un diagnóstico correcto. Las pruebas de laboratorio son necesarias para llevar a cabo las medidas pertinentes en cada paciente. En México, el riesgo de sindemia de COVID-19 y dengue es alto, por lo que puede colapsar los sistemas de salud. Los estados del sureste y los colindantes con el Pacífico requieren especial atención ya que presentan condiciones geográficas, ambientales y climáticas que favorecen la rápida propagación del dengue y COVID-19. La infección simultánea empeorará la situación epidemiológica, complicará el diagnóstico, control y tratamiento de ambas enfermedades.

Abstract A syndemic is the convergence of two or more diseases in the same space and time. In Mexico, the dengue epidemic is active and predominates in areas of the Pacific and the Gulf of Mexico; in turn, the COVID-19 epidemic severely affects the same areas as dengue fever. Given that both these diseases share many clinical manifestations, in areas where tropical diseases are endemic, it is important to make careful evaluations of the patient who consults for fever in order to establish a timely diagnosis. Laboratory diagnostic tests are necessary to take the pertinent measures for each patient. In Mexico, the risk of a syndemic between COVID-19 and dengue fever is high, and thus it that can collapse health systems. The states of southeastern Mexico and the Pacific region require special attention, since they have geographic, environmental and climatic conditions that favor the rapid spread of dengue and COVID-19. Simultaneous infection will worsen the epidemiological situation, and complicate the diagnosis, control and treatment of both diseases.

Exploratory analysis of polygenic risk scores for psychiatric disorders: Applied to dual diagnosis

Background Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). Methods We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. Results We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. Conclusions Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations.

Association study between the MDR1 gene and clinical characteristics in schizophrenia

Objective: Schizophrenia is a complex psychiatric disorder, characterized by disturbed patterns of thought and affecting 0.3-2.0% of the world population. Previously, the multidrug resistance 1 (MDR1) gene has been associated with schizophrenia in treatment response studies in psychotic patients. The aim of this study was to determine the association between MDR1 gene polymorphisms and clinical characteristics in patients with schizophrenia. Methods: Positive and negative symptoms of schizophrenia were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) in 158 Mexican patients with schizophrenia. Analyses of MDR1 gene polymorphisms were performed using TaqMan technology. A multivariate ANOVA was performed with MDR1 polymorphisms and gender as independent variables. Results: Males with the G/G genotype of MDR1 rs2032582 presented significantly higher levels of delusions (p = 0.02). When comparing female vs. male groups, the difference was statistically significant (p = 0.0003). Analyses of the MDR1 gene rs1045642 variant showed no significant differences. Conclusion: Our findings suggest that male carriers of the G allele of variant rs2032582 exhibit greater severity of delusions; however, these results should be taken as preliminary, and replication studies in other populations of different ethnic origins are required to confirm these findings. .