Antidepressants increase neural progenitor cells in the human hippocampus

By M. Boldrini, M. Underwood, R. Hen, G. Rosoklija, A. Dwork, J. Mann, V. Arango. 2009

696 citations recorded by the source corpus.

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 (p⩽0.001) and controls (p⩽0.001), 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 (p⩽0.001), SSRI-treated MDD (p=0.001), and controls (p⩽0.001). 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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Developmental Neuroscience

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. R. Hen
2. G. Agam
3. R. Belmaker
4. Amar Sahay
5. Robin L. Carhart-Harris
6. B. R. Miller
7. A. Dwork
8. G. Rosoklija

In Cognitive Neuroscience

1. Robin L. Carhart-Harris
2. R. Hen
3. G. Agam
4. David J. Nutt
5. Amar Sahay
6. R. Belmaker

In Developmental Neuroscience

1. R. Hen
2. G. Agam
3. R. Belmaker
4. Amar Sahay
5. B. R. Miller
6. V. Arango
7. A. Dwork
8. G. Rosoklija

Citations in the corpus

• Human Hippocampal Neurogenesis Persists throughout Aging (2018, neutral): “We estimated the volume of the anterior, mid, and posterior DG, including the volumes of GCL, molecular layer (ML), and SGZ, using the Cavalieri method (Simić et al., 1997), as previously reported (Boldrini et al., 2009, 2013).”
• Early maternal deprivation affects dentate gyrus structure and emotional learning in adult female rats (2010, neutral): “2001), cytogenesis (Boldrini et al. 2009; Lucassen et al. 2010b) and neuron (Stockmeier et al.”
• The current state of the neurogenic theory of depression and anxiety. (2015, background): “A second study that included confirmation of medication adherence, found a significant increase in neuronal progenitor cells and dividing cells in the dentate gyrus [26].”
• Benzodiazepines And The Potential Trophic Effect Of Antidepressants On Dentate Gyrus Cells In Mood Disorders (2014, positive): “Immunohistochemistry and stereology were performed as previously described (Boldrini et al., 2009, 2012, 2013).”
• Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors (2015, background): “This disparity, along with the findings that antidepressants increase the number of adult-born neurons (Boldrini et al, 2009; Malberg et al, 2000), which take about 4 weeks to form synaptic connections (Toni et al, 2007) and contribute to behavior in rodents (Denny et al, 2012; Kee et al, 2007),…”
• Major depressive disorder. (2008, positive): “pal neurogenesis in rodents [58,62,63].”
• Serotonin and brain function: a tale of two receptors (2017, background): “Chronic treatment with SSRIs has been associated with increased neurogenesis (Boldrini et al., 2009), particularly in the hippocampus (Boldrini et al., 2009, 2012) and some improvements in learning and cognition (Bui et al., 2013), albeit with some contradictory findings (Deakin et al., 2004).”