Through the looking glass: examining neuroanatomical evidence for cellular alterations in major depression

Alterations in brain plasticity are increasingly thought to play important roles in major depressive disorder (MDD) and suicide. To gain a better understanding of the gross structural changes observed in the brains of major depressed and suicide subjects, a number of recent investigations have scrutinized the cellular integrity of brain regions implicated in mood disorders. The purpose of this review is to summarize the current knowledge on the microscopic features of neuronal and glial cell populations in these different brain regions, namely the prefrontal cortex, hippocampus, amygdala, raphe nucleus and locus coeruleus. In general, evidence from this burgeoning field supports the hypothesis of altered cell plasticity in MDD and suicide occurring mainly in key fronto-limbic areas. Interestingly, reported morphometric and cell density alterations are generally region-specific and implicate several neuromodulatory systems, notably GABAergic, serotonergic, noradrenergic and glutamatergic pathways. Cell-specific changes involve reductions in densities of astrocytes and oligodendrocytes, while increases in microglial densities have also been reported. Furthermore, increases in neuronal densities have been found in subcortical regions. The implication of such findings for our understanding of the cellular and molecular underpinnings of MDD and suicide are discussed, and the strengths and weaknesses of morphological approaches used to analyse human postmortem brain tissues are evaluated.