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 DOI: 10.1016/j.pscychresns.2026.112229 via PubMed
Summary
AI-generated from the abstractIn patients with treatment-resistant depression, higher baseline levels of magnetic substances in the right nucleus accumbens and the left amygdala, measured by brain imaging, predicted a greater reduction in specific depressive symptoms after repeated ketamine infusions. The study included 17 Japanese patients and used a double-blind, randomized placebo-controlled design followed by an open-label phase. Baseline magnetic susceptibility in the right nucleus accumbens correlated with improvement in retardation symptoms, while baseline R2* in the left amygdala correlated with improvement in vegetative symptoms. These brain markers may help predict which patients will benefit from ketamine treatment.
Study at a glance
| Characteristics | Double-blind, randomized placebo-controlled trial followed by an extended single-arm open-label study Peer reviewed |
|---|---|
| Sample size | 17 |
| Population | Japanese patients with treatment-resistant depression |
| Topics | Depression Ketamine |
| Keywords | Amygdala Double-blind Magnetic resonance imaging Placebo-controlled trial |
| Key finding | Baseline magnetic substances in the right nucleus accumbens and left amygdala predicted antidepressant effects of repeated ketamine infusions in patients with treatment-resistant depression. |
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.