Oral ketamine effects on dynamics of functional network connectivity in patients treated for chronic suicidality.

Ketamine treatment for chronic suicidality alters how brain networks synchronize and transition over time. In a 6-week open-label trial with 29 patients, those who received ketamine showed significantly more transitions among whole-brain connectivity states after treatment. At a 10-week follow-up, patients spent more time in and more frequently visited a highly synchronized brain state, and these changes correlated with reduced suicidal ideation scores. Patients who persistently responded to ketamine had a higher baseline fraction of a cognitive control network state with strong connections, suggesting that pre-treatment brain connectivity patterns may help predict who will benefit from ketamine therapy. These findings point to a biological mechanism for ketamine's suicide-prevention effects.

Study at a glance

Abstract

The underlying brain mechanisms of ketamine in treating chronic suicidality and the characteristics of patients who will benefit from ketamine treatment remain unclear. To address these gaps, we investigated temporal variations of brain functional synchronisation in patients with suicidality treated with ketamine in a 6-week open-label oral ketamine trial. The trial's primary endpoint was the Beck Scale for Suicide Ideation (BSS). Patients who experienced greater than 50% improvement in BSS scores or had a BSS score less than 6 at the post-treatment and follow-up (10 weeks) visits were considered responders and persistent responders, respectively. The reoccurring and transient connectivity pattern (termed brain state) from 29 patients (45.6 years ± 14.5, 15 females) were investigated by dynamic functional connectivity analysis of resting-state functional MRI at the baseline, post-treatment, and follow-up. Post-treatment patients showed significantly more (FDR-Q = 0.03) transitions among whole brain states than at baseline. We also observed increased dwelling time (FDR-Q = 0.04) and frequency (FDR-Q = 0.04) of highly synchronised brain state at follow-up, which were significantly correlated with BSS scores (both FDR-Q = 0.008). At baseline, persistent responders had higher fractions (FDR-Q = 0.03, Cohen's d = 1.39) of a cognitive control network state with high connectivities than non-responders. These findings suggested that ketamine enhanced brain changes among different synchronisation patterns and enabled high synchronisation patterns in the long term, providing a possible biological pathway for its suicide-prevention effects. Moreover, differences in cognitive control states at baseline may be used for precise ketamine treatment planning.