Cell loss and impaired neuroplasticity in prefrontal cortex and hippocampus in major depressive disorder (MDD)

Studies in postmortem brain reveal changes in the density and size of neurons and glia in cerebral cortex and the hippocampus. Molecular mechanisms may underlie these changes and volume decreases in depression. In situ hybridization and immunohistochemistry were used to estimate expression of mRNA for tyrosine kinase B (TrkB), length of axons expressing the serotonin transporter (SERT) and expression of polysialylated neural cell adhesion molecule (PSA-NCAM) in the hippocampus of subjects with MDD and control subjects. In MDD, there was a signifi cant decrease in expression of mRNA for TrkB, the receptor for brain-derived neurotrophic factor, in CA2/3, and in the mean total length of axons expressing SERT-immunoreactivity (IR) in CA1. Area fraction of PSA-NCAM-IR was signifi cantly increased in the hilus only in MDD with an antidepressant prescription.Decreased expression of TrkB receptor mRNA may affect cell survival and synaptic plasticity in depression. The decrease in length of axons expressing the serotonin transporter suggests a decrease in neuropil or in serotonergic innervation of CA1 in depression. The role of PSA-NCAM in establishing synaptic contacts and regulating neurite growth may be increased in subjects treated for depression. Cellular changes at the microscopic level plus neuroimaging changes detected in vivo provides an integration of clinical and basic research for disentangling the pathophysiology of depression.