Gene expression alterations in bipolar disorder postmortem brains
Open accessAbstract
Objectives: Bipolar disorder (BD) is a mental illness of unknown neuropathology and has several genetic associations. Antipsychotics are effective for the treatment of acute mania, psychosis, or mixed states in individuals with BD. We aimed to identify gene transcripts differentially expressed in postmortem brains from antipsychotics‐exposed individuals with BD (hereafter the ‘exposed’ group), non‐exposed individuals with BD (hereafter the ‘non‐exposed’ group), and controls. Methods: We quantified the abundance of gene transcripts in postmortem brains from seven exposed individuals, seven non‐exposed individuals, and 12 controls with the Affymetrix U133P2 GeneChip microarrays and technologies. We applied a q‐value of ≤0.005 to identify statistically significant transcripts with mean abundance differences between the exposed, non‐exposed and control groups. Results: We identified 2191 unique genes with significantly altered expression levels in non‐exposed brains compared to those in the control and exposed groups. The expression levels of these genes were not significantly different between exposed brains and controls, suggesting a normalization effect of antipsychotics on the expression of these genes. Gene ontology (GO) enrichment analysis showed significant (Bonferroni p ≤ 0.05) clustering of subgroups of the 2191 genes under many GO terms; notably, the protein products of genes enriched are critical to the function of synapses, affecting, for example, intracellular trafficking and synaptic vesicle biogenesis, transport, release and recycling, as well as organization and stabilization of the node of Ranvier. Conclusions: These results support a hypothesis of synaptic and intercellular communication impairment in BD. The apparent normalization of expression patterns with exposure to antipsychotic medication may represent a physiological process that relates both to etiology and improvement patterns of the disorder.
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FKBP5 was associated with MDD, bipolar disorder, schizophrenia, PTSD, ADHD, chronic pain, and metabolic dysfunction, insulin resistance and obesity.
“In addition, FKBP5 was associated with MDD [111], bipolar disorder [112], schizophrenia [113], posttraumatic stress disorder [114, 115], attention deficit hyperactivity disorder (ADHD) [116], chronic pain [117, 118] and metabolic dysfunction, insulin resistance and obesity [119, 120].”
From The HPA Axis as Target for Depression (2024) · cites this paper as [112]
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“In addition, FKBP5 was associated with MDD [111], bipolar disorder [112], schizophrenia [113], posttraumatic stress disorder [114, 115], attention deficit hyperactivity disorder (ADHD) [116], chronic pain [117, 118] and metabolic dysfunction, insulin resistance and obesity [119, 120].”
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- Authors
- Chen, H., Wang, N., Zhao, X., Ross, C. A., O’Shea, K. S., & McInnis, M. G.
- Affiliations
- University of Michigan (US)
- Johns Hopkins University (US)
- Corresponding author
- McInnis, Melvin G
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2013-01-30
- Volume
- 15
- Issue
- 2
- Pages
- 177-187
- ISSN
- 1398-5647 (ISSN-L)
- 1399-5618
- PMC
- PMC3582727
- OpenAlex
- W1837914225
- Cited by
- 46
- References
- 52
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 2 · 2013: 3
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- University of Michigan
- Johns Hopkins University
- National Institutes of Health
- Medical School, University of Michigan
- National Institute of Mental Health (MH070775, R01MH070775, K01MH064596)
- National Institute on Drug Abuse (U54DA021519)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- bipolar disorder, gene expression, postmortem brain, antipsychotic drugs, transcriptome, synaptic function, synaptic vesicle biogenesis, nodes of Ranvier, gene ontology enrichment
- MeSH terms
- Adult, Bipolar Disorder, Brain, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Nerve Tissue Proteins, Postmortem Changes, Antipsychotic Agents, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Adaptor Proteins, Vesicular Transport, Eukaryotic Initiation Factors
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