Amygdala and anterior cingulate transcriptomes from individuals with bipolar disorder reveal downregulated neuroimmune and synaptic pathways

• Published in: Nature neuroscience Vol. 25; no. 3; pp. 381 - 389
• Main Authors: Zandi, Peter P., Jaffe, Andrew E., Goes, Fernando S., Burke, Emily E., Collado-Torres, Leonardo, Huuki-Myers, Louise, Seyedian, Arta, Lin, Yian, Seifuddin, Fayaz, Pirooznia, Mehdi, Ross, Christopher A., Kleinman, Joel E., Weinberger, Daniel R., Hyde, Thomas M.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2022; Nature Publishing Group
• Subjects: 631/208/191/2018; 692/699/476/1333; Amygdala; Amygdala - metabolism; Animal Genetics and Genomics; Autopsy; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Bipolar disorder; Bipolar Disorder - genetics; Bipolar Disorder - metabolism; Brain - metabolism; Cortex (cingulate); Gene expression; Gene mapping; Genes; Genetic diversity; Genetic variance; Genomes; Gyrus Cinguli - metabolism; Humans; Inflammation; Neurobiology; Neurosciences; Quantitative trait loci; Resource; Transcription; Transcriptome; Transcriptomes
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/s41593-022-01024-6

Recent genetic studies have identified variants associated with bipolar disorder (BD), but it remains unclear how brain gene expression is altered in BD and how genetic risk for BD may contribute to these alterations. Here, we obtained transcriptomes from subgenual anterior cingulate cortex and amygdala samples from post-mortem brains of individuals with BD and neurotypical controls, including 511 total samples from 295 unique donors. We examined differential gene expression between cases and controls and the transcriptional effects of BD-associated genetic variants. We found two coexpressed modules that were associated with transcriptional changes in BD: one enriched for immune and inflammatory genes and the other with genes related to the postsynaptic membrane. Over 50% of BD genome-wide significant loci contained significant expression quantitative trait loci (QTL) (eQTL), and these data converged on several individual genes, including SCN2A and GRIN2A . Thus, these data implicate specific genes and pathways that may contribute to the pathology of BD. The authors obtained transcriptomes from anterior cingulate cortex and amygdala samples from post-mortem brains of individuals with bipolar disorder and neurotypical controls. They observed decreased expression of neuroimmune and synaptic pathways.