Rebuilding the atrophied brain: 6-month nasal esketamine therapy expands key frontal and hippocampal regions and reduces serum neurofilament levels in patients with major depressive disorder. A proof-of-concept study of the depTesk (DEPression treatment with ESKetamine) study
Ana Rodríguez Lorente, María Pilar Campos-Navarro, Ángela Gil Montoya, Celia Marín Pérez, María Luisa Maso Navarro, Tomás Orgaz Morales, Nuria López Ramirez, Juan Antonio García-Carmona
CNS Spectrums 2025 DOI: 10.1017/s1092852925100631 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Proof-of-concept study Peer reviewed |
|---|---|
| Sample size | 7 |
| Population | Patients with treatment-resistant depression |
| Interventions | Intranasal esketamine oral antidepressants |
| Duration | 6 months |
| Measures | VolBrain2, DSI studio, neurofilament light chain (sNfL) |
| Topics | Depression Esketamine |
| Key points | In seven patients with treatment-resistant depression, six months of intranasal esketamine alongside oral antidepressants was associated with increased brain volume in the frontal cortex, anterior cingulate, and hippocampus, and in fiber tracts linked to emotional regulation, while neurofilament light chain levels decreased. The authors suggest these changes may reflect structural remodeling and potential neuroprotective effects. |
Abstract
Abstract Objectives This proof-of-concept study aimed to assess the impact of intranasal esketamine (ESK-IN) in brain volume and neurofilament light chain (sNfL) over 6-months in patients with treatment resistant depression (TDR).
Methods: Seven TRD patients received ESK-IN while continuing oral antidepressants. Clinical evaluations were conducted at baseline, 1, 3, and 6 months, with MRI scans and blood samples taken at baseline and 6 months. Brain volume was assessed using VolBrain2 and DSI studio.
Results: Compared to controls, TRD patients initially showed lower volumes (mm 3 ) in key cortical regions such as the insula (p = 0.0156), the frontal lobe (p = 0.0228) the superior parietal lobe (p = 0.0402), both superior (p = 0.0216) and inferior (p = 0.0437) temporal lobes and subcortical regions such as the nucleus accumbens (p = 0.0056), putamen (p = 0.0083), thalamus (p = 0.0102) and the hippocampus (p = 0.0001). Brain volume increased in the frontal cortex (p = 0.0295), the anterior cingulate (p = 0.0496), and hippocampus (p = 0.0015), as well as in the volume and fiber tracts associated with emotional regulation, such as the frontoparahippocampal (p = 0.0156 and p = 0.0313, respectively), the frontoparietal (p = 0.0496 and p = 0.0156, respectively) and the frontal aslant tract after 6 months on treatment with ESK-IN. In parallel, sNfL levels decreased post-treatment, indicating potential neuroprotective effects.
Conclusions: ESK-IN may promote structural changes in regions associated with mood regulation and neuroplasticity, while also reducing neuronal damage in TRD patients.