# Relationship between hippocampal volume and treatment response before and after escitalopram administration in patients with depression

**Authors:** Toshiharu kamishikiryo, Eri itai, Yuki mitsuyama, Yoshikazu masuda, Osamu yamamoto, Tatsuji tamura, Hiroaki jitsuiki, Akio mantani, Norio yokota, Go okada

PMC · DOI: 10.1038/s41398-025-03796-4 · Translational Psychiatry · 2025-12-30

## TL;DR

This study found that people with depression who responded to escitalopram had specific changes in their hippocampal volume and structure before and after treatment.

## Contribution

The study identifies baseline hippocampal volume and laterality as potential predictors of escitalopram treatment response in depression.

## Key findings

- Responders had larger left hippocampal volume and leftward laterality at baseline compared to nonresponders.
- Escitalopram increased right hippocampal and right hippocampal head volume in responders.
- Volume changes in the right hippocampus correlated with improvements in core depressive symptoms.

## Abstract

The hippocampus plays a crucial role in memory formation and emotional regulation, and is closely related to the pathology of depression. Escitalopram, a selective serotonin reuptake inhibitor, promotes neurogenesis in the dentate gyrus of the hippocampus and alters its structure. This study examined the relationship between these escitalopram-induced structural changes and treatment response in 107 patients with moderate to severe depression, of whom 56 were female (52.3%), with a mean age of 41.5 years (range: 25–73 years). Follow-up data were available for 71 patients (66.4%). Changes in the volume and laterality of hippocampal subregions were compared before and after escitalopram treatment between Responders to escitalopram (n = 53) and Nonresponders (n = 54). The results indicated that Responders had a larger left hippocampal volume (β = 189.3, 95% CI [71.4, 307.2], Cohen’s f² ≈ 0.094) and greater leftward laterality (β = 0.012, 95% CI [2.2 × 10⁻⁴, 0.024], Cohen’s f² ≈ 0.04) than Nonresponders at baseline. Additionally, the right hippocampus and right hippocampal head exhibited increased volume (β = 80.6, 95% CI [28.5, 132.8], Cohen’s f² ≈ 0.005; β = 50.4, 95% CI [22.2, 78.5], Cohen’s f² ≈ 0.006) and altered laterality (β = −0.011, 95% CI [−0.022, −4.1 × 10⁻⁴], Cohen’s f² ≈ 0.003; β = −3.3 × 10⁻⁴, 95% CI [−5.7 × 10⁻⁴, −8.3 × 10⁻⁵], Cohen’s f² ≈ 0.006) in response to escitalopram in Responders compared to Nonresponders. Furthermore, the volume changes in the right hippocampus and right hippocampal head correlated with core depressive symptoms. It is suggested that these volume changes play an important role in the improvement of core symptoms of depression by escitalopram treatment. These findings can help to reveal the mechanisms of action of selective serotonin reuptake inhibitors and have the potential to facilitate the early identification of patients who will respond to treatment.

## Linked entities

- **Chemicals:** escitalopram (PubChem CID 146570)
- **Diseases:** depression (MONDO:0002050)

## Full-text entities

- **Diseases:** depression (MESH:D003866)
- **Chemicals:** Escitalopram (MESH:D000089983), serotonin (MESH:D012701)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC12783789/full.md

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Source: https://tomesphere.com/paper/PMC12783789