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

Peter P. Zandi; Andrew E. Jaffe; Fernando S. Goes; Emily E. Burke; Leonardo Collado-Torres; Louise Huuki-Myers; Arta Seyedian; Yian Lin; Fayaz Seifuddin; Mehdi Pirooznia; Christopher A. Ross; Joel E. Kleinman; Daniel R. Weinberger; Thomas M. Hyde

doi:10.1038/s41593-022-01024-6

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

Peter P. Zandi, Andrew E. Jaffe, Fernando S. Goes, Emily E. Burke, Leonardo Collado-Torres, Louise Huuki-Myers, Arta Seyedian, Yian Lin, Fayaz Seifuddin, Mehdi Pirooznia, Christopher A. Ross, Joel E. Kleinman, Daniel R. Weinberger, Thomas M. Hyde

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Abstract

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 BP.

Original language	English (US)
Pages (from-to)	381-389
Number of pages	9
Journal	Nature neuroscience
Volume	25
Issue number	3
DOIs	https://doi.org/10.1038/s41593-022-01024-6
State	Published - Mar 2022

ASJC Scopus subject areas

General Neuroscience

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Zandi, P. P., Jaffe, A. E., Goes, F. S., Burke, E. E., Collado-Torres, L., Huuki-Myers, L., Seyedian, A., Lin, Y., Seifuddin, F., Pirooznia, M., Ross, C. A., Kleinman, J. E., Weinberger, D. R., & Hyde, T. M. (2022). Amygdala and anterior cingulate transcriptomes from individuals with bipolar disorder reveal downregulated neuroimmune and synaptic pathways. Nature neuroscience, 25(3), 381-389. https://doi.org/10.1038/s41593-022-01024-6

Zandi, PP, Jaffe, AE, Goes, FS, Burke, EE, Collado-Torres, L, Huuki-Myers, L, Seyedian, A, Lin, Y, Seifuddin, F, Pirooznia, M, Ross, CA , Kleinman, JE , Weinberger, DR & Hyde, TM 2022, 'Amygdala and anterior cingulate transcriptomes from individuals with bipolar disorder reveal downregulated neuroimmune and synaptic pathways', Nature neuroscience, vol. 25, no. 3, pp. 381-389. https://doi.org/10.1038/s41593-022-01024-6

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title = "Amygdala and anterior cingulate transcriptomes from individuals with bipolar disorder reveal downregulated neuroimmune and synaptic pathways",

abstract = "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 BP.",

author = "Zandi, {Peter P.} and Jaffe, {Andrew E.} and Goes, {Fernando S.} and Burke, {Emily E.} and Leonardo Collado-Torres and Louise Huuki-Myers and Arta Seyedian and Yian Lin and Fayaz Seifuddin and Mehdi Pirooznia and Ross, {Christopher A.} and Kleinman, {Joel E.} and Weinberger, {Daniel R.} and Hyde, {Thomas M.}",

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doi = "10.1038/s41593-022-01024-6",

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AU - Zandi, Peter P.

AU - Jaffe, Andrew E.

AU - Goes, Fernando S.

AU - Burke, Emily E.

AU - Collado-Torres, Leonardo

AU - Huuki-Myers, Louise

AU - Seyedian, Arta

AU - Lin, Yian

AU - Seifuddin, Fayaz

AU - Pirooznia, Mehdi

AU - Ross, Christopher A.

AU - Kleinman, Joel E.

AU - Weinberger, Daniel R.

AU - Hyde, Thomas M.

PY - 2022/3

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N2 - 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 BP.

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

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