Abstract
Background
Dual diagnosis is the co-occurrence of at least one substance use disorder (SUD) and one or more mental disorders in a given individual. Despite this comorbidity is highly prevalent and associated with adverse clinical outcomes, its neurobiology remains unclear. Furthermore, patients with dual diagnosis 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 dual diagnosis 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 SUD alone (n=10), suicides with mood disorders alone (n=13), and suicides without mental comorbidities (n=5). Gene expression profiles were assessed by microarrays. Microarray data quality control was performed. Then, microarray data were background corrected and quantile normalized. Differentially expressed genes among the conditions were identified by a linear model implemented in the limma package.
Results
When comparing the transcriptome of suicides with dual diagnosis to suicides with SUD alone and suicides with mood disorders alone, we identified 255 and 172 differentially expressed genes, respectively. When comparing suicides with DD to suicides without mental comorbidities, we identified 330 differentially expressed genes, mainly enriched in neurogenesis.
Discussion
Our results suggest that suicides with dual diagnosis present a gene expression profile distinct from that of suicides with a single disorder and suicides without mental disorders. Also, suicides with dual diagnosis, SUD and mood disorders exhibited alterations in the expression of synaptic genes. However, suicides with each condition (dual diagnosis, SUD or mood disorders) exhibited unique gene expression changes at different levels within synaptic signaling. These gene expression differences might contribute to the phenotypical and clinical discrepancies observed in patients with dual diagnosis and patients with a single disorder