Anterior default mode network and posterior insular connectivity is predictive of depressive symptom reduction following serial ketamine infusion.
Benjamin S C Wade, Joana Loureiro, Ashish Sahib, Antoni Kubicki, Shantanu H Joshi, Gerhard Hellemann, Randall T Espinoza, Roger P Woods, Eliza Congdon, Katherine L Narr
Psychological medicine September 1, 2022 Peer reviewed DOI: 10.1017/s0033291722001313 via PubMed
Summary
In patients with depression, pretreatment neuroimaging measures can predict changes in depressive symptoms following serial ketamine infusion. Specifically, increased connectivity in certain brain regions and lower kurtosis in the superior longitudinal fasciculus were associated with reduced symptoms on the HDRS-6 and core mood and anhedonia scales. The study involved 60 patients who underwent multimodal neuroimaging before treatment and were assessed for symptom changes after receiving four ketamine infusions.
Study at a glance
| Design | observational cohort |
|---|---|
| Sample size | 60 |
| Population | patients with major depressive disorder |
| Key finding | Increased connectivity in the right medial prefrontal cortex/anterior cingulate and posterior insula predicted reduced depressive symptoms following ketamine treatment. |
Abstract
Ketamine is a rapidly-acting antidepressant treatment with robust response rates. Previous studies have reported that serial ketamine therapy modulates resting state functional connectivity in several large-scale networks, though it remains unknown whether variations in brain structure, function, and connectivity impact subsequent treatment success. We used a data-driven approach to determine whether pretreatment multimodal neuroimaging measures predict changes along symptom dimensions of depression following serial ketamine infusion. Patients with depression (n = 60) received structural, resting state functional, and diffusion MRI scans before treatment. Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17), the Inventory of Depressive Symptomatology (IDS-C), and the Rumination Response Scale (RRS) before and 24 h after patients received four (0.5 mg/kg) infusions of racemic ketamine over 2 weeks. Nineteen unaffected controls were assessed at similar timepoints. Random forest regression models predicted symptom changes using pretreatment multimodal neuroimaging and demographic measures. Two HDRS-17 subscales, the HDRS-6 and core mood and anhedonia (CMA) symptoms, and the RRS: reflection (RRSR) scale were predicted significantly with 19, 27, and 1% variance explained, respectively. Increased right medial prefrontal cortex/anterior cingulate and posterior insula (PoI) and lower kurtosis of the superior longitudinal fasciculus predicted reduced HDRS-6 and CMA symptoms following treatment. RRSR change was predicted by global connectivity of the left posterior cingulate, left insula, and right superior parietal lobule. Our findings support that connectivity of the anterior default mode network and PoI may serve as potential biomarkers of antidepressant outcomes for core depressive symptoms.