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Identifying brain connectivity patterns linked to placebo response could guide more personalized approaches to depression treatment.
Ketamine (fast-acting antidepressant) is commonly used for patients with treatment-resistant depression (TRD). But, as TRD varies significantly among patients, identifying biobehavioral markers is vital to tailoring intravenous Ketamine therapy more effectively. One promising approach is analyzing brain connectivity patterns in networks like the default mode, ventral affective, and cognitive control systems.
In a new randomized controlled trial by Shabnam Hossein and colleagues, neuroimaging was used to map functional connectivity during positive mood processing in 152 patients with TRD. Participants were then randomly allocated to either Ketamine or a placebo (saline). The directed connectivity maps were obtained using the Subgroup-Group Iterative Multiple Model Estimation approach. Data-driven subgroups were detected using the Walktrap algorithm (a widely used community-detection method in psychology). The severity of depression was noted before and 24 hours following Ketamine infusion.
The data-driven analysis revealed two distinct brain connectivity subgroups (Subgroup A with 110 patients and Subgroup B with 42 patients). As found, the treatment response was influenced by the interaction between infusion type and subgroup (p = .040). While the subset did not predict response to Ketamine, it did for placebo. Patients in Subgroup B were more likely than those in the other group to respond to a placebo at 24 hours post-infusion. While Ketamine improved depressive symptoms across both groups, the study suggests that certain brain connectivity patterns may anticipate the placebo response.
Functional connectivity subtypes during a positive mood induction: Predicting clinical response in a randomized controlled trial of ketamine for treatment-resistant depression.
Shabnam Hossein et al.
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