1. ¹Department of Psychiatry, Columbia University, New York, NY, USA
2. ²Division of Molecular Imaging and Neuropathology, Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA
3. ³Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy
4. ⁴Department of Neuroscience, Columbia University, New York, NY, USA
5. ⁵Department of Pharmacology, Columbia University, New York, NY, USA
6. ⁶Division of Integrative Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA
7. ⁷Macedonian Academy of Sciences & Arts, Skopje, Republic of Macedonia
8. ⁸Department of Pathology and Cell Biology, Columbia University, New York, NY, USA

Correspondence: Dr M Boldrini, Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University College of Physicians & Surgeons, New York State Psychiatric Institute, 1051 Riverside Drive, Box 42, New York, NY 10032 USA, Tel: +212 543 5440, Fax: +212 543 6017, E-mail: mb928@columbia.edu

Received 29 April 2009; Revised 9 June 2009; Accepted 10 June 2009; Published online 15 July 2009.

Abstract

Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) increase neurogenesis in the dentate gyrus (DG) of rodents and nonhuman primates. We determined whether SSRIs or TCAs increase neural progenitor (NPCs) and dividing cells in the human DG in major depressive disorder (MDD). Whole frozen hippocampi from untreated subjects with MDD (N=5), antidepressant-treated MDD (MDDT, N=7), and controls (C, N=7) were fixed, sectioned, and immunostained for NPCs and dividing cell markers (nestin and Ki-67, respectively), NeuN and GFAP, in single and double labeling. NPC and dividing cell numbers in the DG were estimated by stereology. Clinical data were obtained by psychological autopsy, and by toxicological and neuropathological examination performed on all subjects. NPCs decreased with age (p=0.034). Females had more NPCs than males (p=0.023). Correcting for age and sex, MDDT receiving SSRIs had more NPCs than untreated MDD (p0.001) and controls (p0.001), NPCs were not different in SSRI- and TCA-treated MDDT (p=0.169). Dividing cell number, unaffected by age or sex, was greater in MDDT receiving TCAs than in untreated MDD (p0.001), SSRI-treated MDD (p=0.001), and controls (p0.001). The increase of NPCs and dividing cells in MDDT was localized to the rostral DG. MDDT had a larger DG volume compared with untreated MDD or controls (p=0.009). Antidepressants increase NPC number in the anterior human DG. Whether this finding is critical or necessary for the antidepressants effect remains to be determined.