TY - JOUR
T1 - Changes in hippocampal volume, 5-HT4 receptor binding, and verbal memory over the course of antidepressant treatment in major depressive disorder
AU - Jensen, Kristian H.Reveles
AU - Dam, Vibeke H.
AU - Köhler-Forsberg, Kristin
AU - Ozenne, Brice
AU - Stenbæk, Dea S.
AU - Ganz, Melanie
AU - Fisher, Patrick Mac Donald
AU - Frokjaer, Vibe Gedsoe
AU - Knudsen, Gitte M.
AU - Jørgensen, Martin Balslev
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2025
Y1 - 2025
N2 - Serotonin reuptake inhibitors have been reported to increase hippocampal volume and improve memory function in patients with Major depressive disorder (MDD). The postsynaptic 5-HT4 receptor (5-HT4R) is involved in hippocampal development, familial risk for depression and depressive pathology. In an open-label trial with 91 patients (72% female, mean 27.2 years) with MDD, we investigated the relation between changes in hippocampal volume, 5-HT4R, and verbal memory during 12 weeks treatment with 10–20 mg escitalopram. Depression severity, verbal memory, MRI-determined hippocampus volume and PET-determined 5-HT4R were measured pretreatment. Forty-three patients were rescanned at week 8. HAMD17 was reassessed at week 8 and together with verbal memory at week 12. We used mixed-effects models and linear regressions. We estimated a 27 mm3 (p = 0.086) reduction in mean hippocampus volume over the course of eight weeks. In patients clinically responding to treatment, we estimated a 45 mm3 reduction (p = 0.019), 8 mm3 increase in non-responders (p = 0.78), and a 52 mm3 group difference (p = 0.12). Hippocampal 5-HT4 receptor binding before treatment and at week eight was negatively associated with hippocampal volume in females, regardless of treatment response (p-values≤0.006). However, no clear evidence for an association in males or sex interaction could be established (p-values≥0.16). Although the hippocampus volume did not increase with treatment, we found a decrease in clinically responsive patients. Our findings suggest an association between 5-HT4R signalling and changes in hippocampal volume in females with MDD during antidepressant treatment, highlighting the need for further investigation into the role of serotonergic mechanisms in hippocampal plasticity.
AB - Serotonin reuptake inhibitors have been reported to increase hippocampal volume and improve memory function in patients with Major depressive disorder (MDD). The postsynaptic 5-HT4 receptor (5-HT4R) is involved in hippocampal development, familial risk for depression and depressive pathology. In an open-label trial with 91 patients (72% female, mean 27.2 years) with MDD, we investigated the relation between changes in hippocampal volume, 5-HT4R, and verbal memory during 12 weeks treatment with 10–20 mg escitalopram. Depression severity, verbal memory, MRI-determined hippocampus volume and PET-determined 5-HT4R were measured pretreatment. Forty-three patients were rescanned at week 8. HAMD17 was reassessed at week 8 and together with verbal memory at week 12. We used mixed-effects models and linear regressions. We estimated a 27 mm3 (p = 0.086) reduction in mean hippocampus volume over the course of eight weeks. In patients clinically responding to treatment, we estimated a 45 mm3 reduction (p = 0.019), 8 mm3 increase in non-responders (p = 0.78), and a 52 mm3 group difference (p = 0.12). Hippocampal 5-HT4 receptor binding before treatment and at week eight was negatively associated with hippocampal volume in females, regardless of treatment response (p-values≤0.006). However, no clear evidence for an association in males or sex interaction could be established (p-values≥0.16). Although the hippocampus volume did not increase with treatment, we found a decrease in clinically responsive patients. Our findings suggest an association between 5-HT4R signalling and changes in hippocampal volume in females with MDD during antidepressant treatment, highlighting the need for further investigation into the role of serotonergic mechanisms in hippocampal plasticity.
KW - Escitalopram
KW - Hippocampus
KW - Hippocampus volume
KW - Major depressive disorder
KW - SSRI
KW - Verbal memory
U2 - 10.1016/j.jpsychires.2024.11.043
DO - 10.1016/j.jpsychires.2024.11.043
M3 - Journal article
C2 - 39616866
AN - SCOPUS:85210390275
VL - 181
SP - 197
EP - 205
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
SN - 0022-3956
ER -