Laboratorio de Genética y Genómica de Enfermedades Neuropsiquíatricas

About the lab

Objetivo: El foco del laboratorio es contribuir a entender la genética de las enfermedades neurológicas y psiquiátricas. La etiología de estas enfermedades involucra diversos mecanismos genéticos, los cuales explican la heterogeneidad clínica y la interacción genes-ambiente. Nosotros estamos especialmente interesados en analizar la heterogeneidad como vía para entender la arquitectura genética de las enfermedades, por lo que nosotros usamos diversos modelos y estrategias metodológicas. Las nuevas tecnologías de secuenciación han permitido que el diagnostico y el descubrimiento de nuevas enfermedades sean complementarios permitiendo su aplicación clínica y en investigación.

Featured research (2)

Background Approximately 30% of individuals with schizophrenia (SZ) are resistant to conventional antipsychotic drug therapy (AP). Of these, one third are also resistant to the second-line treatment, clozapine. Treatment resistance and refractoriness are associated with increased morbidity and disability, making timely detection of these issues critical. Variability in treatment responsiveness is partly genetic, but research has yet to identify variants suitable for personalizing antipsychotic prescriptions. Methods We evaluated potential associations between response to AP and candidate gene variants previously linked to schizophrenia or treatment response. Two groups of patients with SZ were evaluated; one receiving clozapine (n=135) and the other receiving another second-generation AP (n=61). Single-nucleotide polymorphisms (SNPs) in the genes OXT, OXTR, CNR1, DDC, and DRD2 were analyzed. Results Several SNPs were associated with response vs. resistance to AP or clozapine. Conclusions This is the first study of its kind in our admixed Chilean population to address the complete treatment response spectrum. We identified SNPs predictive of treatment-resistant schizophrenia in the genes OXT, CNR1, DDC, and DRD2.
Objective: Genetic factors underlying different personality traits are not entirely understood, particularly how genes interact to modulate their effect. We studied 76 patients diagnosed with borderline personality disorder (BPD), characterized by extreme levels of personality traits, especially neuroticism (N), in which we genotyped two polymorphisms, the 5HTTLPR of the Serotonin transporter (SERT) gene, and the Val66Met of the Brain-derived neurotrophic factor (BDNF) gene. Results: We found an association with SERT, where S-allele carriers had significantly higher levels of N than L-homozygous. Furthermore, we found that the protective effect of L-homozygosity is only evident on A-allele carriers of the BDNF Val66Met polymorphism. Genetic constitution in SERT and BDNF seems to be important in neuroticism, the most relevant personality trait on BPD.

Lab head

M Leonor Bustamante
  • Program of Human Genetics and Biomedical Sciences Institute and Universitary Psychiatric Clinic
About M Leonor Bustamante
  • M Leonor Bustamante is an Assistant Professor at the Program of Human Genetics of the Biomedical Sciences Institute and at the University Psychiatric Clinic, Faculty of Medicine University of Chile.

Members (1)

Javier Deneken
  • University of Chile

Alumni (1)

Valeria Salinas
  • Hospital General de Agudos JM Ramos Mejía