Gene expression alterations in bipolar disorder postmortem brains.
OBJECTIVE
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.
Department of Psychiatry and Comprehensive Depression Center Molecular and Behavioral Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Haiming
H
Chen
Nulang
N
Wang
Xin
X
Zhao
Christopher A
CA
Ross
K Sue
KS
O'Shea
Melvin G
MG
McInnis
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000473:pathology*; D001921:Brain / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011180:Postmortem Changes
D033942:Adaptor Proteins, Vesicular Transport; D014150:Antipsychotic Agents; D039642:Eukaryotic Initiation Factors; D009419:Nerve Tissue Proteins