Hippocampal subfield analysis to compare the depression and neurodegeneration spectrum

Hippocampal volume (HV) deficits in stress related disorders, particularly recurrent MDD, is supported by a large literature. Lower HV has been associated with poorer short and long term treatment outcome in depression which in turn predisposes to recurrent episodes. Epidemiologically, an association exists between recurrent depressive episodes and dementia, and here we investigate hippocampal subfield profiles between controls, the MDD (first episode [FE], N = 101; recurrent MDD, N = 266) and neurodegeneration spectrum (MCI, N = 29; AD N = 26). To probe disease specificity, 37 patients with schizophrenia were included. FE patients showed no significant deficit; recurrent MDD patients showed total HV (THV) and subregional deficits (CA2/3, CA1). Schizophrenia showed was global brain volume (GBV) and non-localized hippocampal deficits. MCI showed THV and CA-subfield deficits. AD, expectedly, showed gross GBV, THV and subregional deficit, about 10 times stronger (HV: ~ 20% deficit) compared with recurrent MDD (~ 2%). As 2nd approach volume, deficits were estimated by multiple regression on the control sample, revealing stronger effects and unmasking (pre-)subiculum deficits in recurrent MDD. Notably, recurrent MDD and MCI did not differ at the hippocampal, but only the GBV level (p = 0.005). No subfield differences were found between schizophrenia, recurrent MDD and MCI. We mainly conclude that recurrent MDD exhibits total and subfield hippocampal structural deficits in the range of MCI.