Brain iron-sensitive markers (magnetic susceptibility and R2*) predict antidepressant response to ketamine in treatment-resistant depression.
Kengo Yonezawa, Shinichiro Nakajima, Shuhei Shibukawa, Hirohito Kan, Yohei Ohtani, Kie Nomoto-Takahashi, Taisuke Yatomi, Sota Tomiyama, Nobuhiro Nagai, Keisuke Kusudo, Shiori Honda, Nobuaki Hondo, Koki Takahashi, Sotaro Moriyama, Takashige Yamada, Shinsuke Koike, Hiroyuki Uchida, Hideaki Tani
Psychiatry research. Neuroimaging August 1, 2026 Peer reviewed DOI: 10.1016/j.pscychresns.2026.112229 via PubMed
Summary
Baseline magnetic susceptibility in the right nucleus accumbens and R2* in the left amygdala may serve as biomarkers to predict the antidepressant effects of repeated ketamine infusions in patients with treatment-resistant depression (TRD). In a study involving 17 participants, a negative correlation was found between magnetic susceptibility and changes in MADRS retardation symptom scores, as well as between R2* and changes in MADRS vegetative symptom scores.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 17 |
| Population | Japanese patients with treatment-resistant depression |
| Key finding | Baseline magnetic substances in the right nucleus accumbens and the left amygdala may be biomarkers to predict the effect of repeated ketamine infusions in patients with TRD. |
Abstract
Ketamine may alleviate treatment-resistant depression (TRD) primarily through glutamatergic modulation, with downstream dopaminergic activation. Iron plays an important role in monoaminergic metabolism, that is also implicated in the pathophysiology of TRD. Both Quantitative Susceptibility Mapping (QSM) and Effective Transverse Relaxation Rate (R2*) mapping can determine the extent of iron deposition in the brain. Given that abnormal iron accumulation may reflect dopamine dysfunction, we hypothesized that baseline magnetic substances could predict ketamine's antidepressant effects in patients with TRD. We used data from a double-blind, randomized placebo-controlled trial followed by an extended single-arm open-label study to assess the efficacy of repeated intravenous ketamine in Japanese patients with TRD (jRCTs031210124). This study analyzed the data from the participants who underwent QSM and R2* mapping before receiving ketamine in either phase. Multivariable regression analyses were conducted to explore the association between baseline magnetic susceptibility and R2* with change in MADRS total and subdomain scores. This study included 17 patients with TRD (7 women; mean ± standard deviation age, 42.9 ± 10.6 years). Baseline magnetic susceptibility in the right nucleus accumbens negatively correlated with the change in MADRS retardation symptom scores (β = -0.73, p = 0.003). Moreover, baseline R2* in the left amygdala was negatively associated with the change in MADRS vegetative symptom scores (β = -0.71, p = 0.004). Baseline magnetic substances in the right nucleus accumbens and the left amygdala may be biomarkers to predict the effect of repeated ketamine infusions in patients with TRD.