title: Neuropathology of bipolar disorder.
abstract: The literature on the neuropathology of bipolar disorder (BD) is reviewed. Postmortem findings in the areas of pathomorphology, signal transduction, neuropeptides, neurotransmitters, cell adhesion molecules, and synaptic proteins are considered. Decreased glial numbers and density in both BD and major depressive disorder (MDD) have been reported, whereas cortical neuron counts were not different in BD (in Brodmann's areas [BAs] 9 and 24). In contrast, MDD patients showed reductions in neuronal size and density (BA 9, BA 47). There are a number of findings of alterations in neuropeptides and monoamines in BD brains. Norepinephrine turnover was increased in several cortical regions and thalamus, whereas the serotonin metabolite, 5-hydroxyindoleacetic acid, and the serotonin transporter were reduced in the cortex. Several reports further implicated both cyclic adenosine monophosphate and phosphatidylinositol (PI) cascade abnormalities. G protein concentrations and activity increases were found in the occipital, prefrontal, and temporal cortices in BD. In the PI signal cascade, alterations in PKC activity were found in the prefrontal cortex. In the occipital cortex, PI hydrolysis was decreased. Two isoforms of the neural cell adhesion molecules were increased in the hippocampus of BD, whereas the synaptic protein marker, synaptophysin, was not changed. The findings of glial reduction, excess signal activity, neuropeptide abnormalities, and monoamine alterations suggest distinct imbalances in neurochemical regulation. Possible alterations in pathways involving ascending projections from the brain stem are considered. Larger numbers of BD brains are needed to further refine the conceptual models that have been proposed, and to develop coherent models of the pathophysiology of BD.
authors.affiliation: National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Vawter
authors.forename: W J
authors.initials: WJ
authors.lastname: Freed
authors.forename: J E
authors.initials: JE
authors.lastname: Kleinman
mesh_terms: D001344:Autopsy; D001714:Bipolar Disorder / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D001923:Brain Chemistry; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D015398:Signal Transduction
chemical_list: D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins