Brain Gene Expression Profiling of Individuals With Dual Diagnosis Who Died by Suicide
Por:
Cabrera-Mendoza, Brenda, Fresno, Cristobal, Monroy-Jaramillo, Nancy, Fries, Gabriel Rodrigo, Walss-Bass, Consuelo, Glahn, David C., Ostrosky-Wegman, Patricia, Genis-Mendoza A.D., Martínez-Magaña J.J., Romero-Pimentel A.L., Díaz-Otañez C.E., Garcia-Dolores, Fernando, González-Sáenz E.E., Mendoza-Morales R.C., Flores, Gonzalo, Vazquez-Roque, Ruben, Nicolini, Humberto
Publicada:
2 abr 2020
Ahead of Print:
1 nov 2019
Categoría:
Psychiatry and mental health
Resumen:
Objective: Dual diagnosis (DD) is the co-occurrence of at least one
substance use disorder and one or more mental disorders in a given
individual. Despite this comorbidity being highly prevalent and
associated with adverse clinical outcomes, its neurobiology remains
unclear. Furthermore, patients with DD are at higher risk for suicidal
behavior in comparison with single disorder patients. Our objective was
to evaluate brain gene expression patterns in individuals with DD who
died by suicide. Methods: We compared the gene expression profile in the
dorsolateral prefrontal cortex of suicides with DD (n = 10) to the
transcriptome of suicides with substance use disorder alone (n = 10),
suicides with mood disorders (MD) alone (n = 13), and suicides without
mental comorbidities (n = 5). Gene expression profiles were assessed by
microarrays. In addition, we performed a brain cell type enrichment to
evaluate whether the gene expression profiles could reflect differences
in cell type compositions among the groups. Results: When comparing the
transcriptome of suicides with DD to suicides with substance use
disorder alone and suicides with MD alone, we identified 255 and 172
differentially expressed genes (DEG), respectively. The overlap of DEG
between both comparisons (112 genes) highlighted the presence of common
disrupted pathways in substance use disorder and MD. When comparing
suicides with DD to suicides without mental comorbidities, we identified
330 DEG, mainly enriched in neurogenesis. Cell type enrichment indicated
higher levels of glial markers in suicides with DD compared to the other
groups. Conclusions: Suicides with DD exhibited a gene expression
profile distinct from that of suicides with a single disorder, being
substance use disorder or MD, and suicides without mental disorders. Our
results suggest alteration in the expression of genes involved in glial
specific markers, glutamatergic and GABAergic neurotransmission in
suicides with DD compared to suicides with a single disorder and
suicides without mental comorbidities. Alterations in the expression of
synaptic genes at different levels were found in substance use disorder
and MD.
Filiaciones:
Cabrera-Mendoza, Brenda:
Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico
PECEM, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
Fresno, Cristobal:
Computational Genomics Department, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico
Monroy-Jaramillo, Nancy:
Department of Genetics, National Institute of Neurology and Neurosurgery, Mexico City, Mexico
Fries, Gabriel Rodrigo:
Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, United States
Walss-Bass, Consuelo:
Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, United States
Glahn, David C.:
Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, United States
Department of Psychiatry, Harvard Medical School, Boston, MA, United States
Ostrosky-Wegman, Patricia:
Biomedical Research Institute, National Autonomous University of Mexico, Mexico City, Mexico
Genis-Mendoza A.D.:
Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico
Martínez-Magaña J.J.:
Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico
Romero-Pimentel A.L.:
Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico
Díaz-Otañez C.E.:
Department of Pathology, Institute of Forensic Sciences (INCIFO), Mexico City, Mexico
Garcia-Dolores, Fernando:
Department of Pathology, Institute of Forensic Sciences (INCIFO), Mexico City, Mexico
González-Sáenz E.E.:
High Specialty Program in Legal and Forensic Psychiatry, Psychiatric Hospital Fray Bernardino Álvarez, Mexico City, Mexico
Mendoza-Morales R.C.:
Department of Pathology, Institute of Forensic Sciences (INCIFO), Mexico City, Mexico
Flores, Gonzalo:
Neuropsychiatry Laboratory, Institute of Physiology, Meritorious Autonomous University of Puebla, Puebla, Mexico
Vazquez-Roque, Ruben:
Neuropsychiatry Laboratory, Institute of Physiology, Meritorious Autonomous University of Puebla, Puebla, Mexico
Nicolini, Humberto:
Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City, Mexico
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