Blunted Neurogenesis in Major Depression and Normal Levels in High Functioning Antidepressant-Treated Subjects

Abstract

Adult hippocampal neurogenesis is implicated in antidepressant action in rodents and primates, yet relationships to human major depression (MDD) and antidepressant effects are unclear. In postmortem human hippocampus, we found doublecortin (DCX) protein and mRNA+ cells co-expressing neuronal but not astroglial or microglial markers. We defined neuroblasts as DCX+ cells located in the subgranular zone that co-expressed neuron-specific beta-tubulin (TUJ1) or lacked co-expression with neuronal nuclear marker (NeuN). Untreated MDD, regardless of clinical state, had fewer DCX-positive cells and neuroblasts in the rostral dentate gyrus compared with non-psychiatric controls. High-functioning, but not low-functioning, antidepressant-treated MDD, exhibited more DCX/TUJ1+ neuroblasts than untreated MDD. Groups did not differ in number of immature neurons, defined as DCX/NeuN+ cells in the inner granule cell layer. Deficient neuroblasts may be linked to hippocampal-dependent cognitive deficits in MDD. Similar neuroblast number between controls and higher-functioning antidepressant treated subjects warrants evaluation of neuroblasts as a treatment target.