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Ketamine induces multiple individually distinct whole-brain functional connectivity signatures

Summary

This study examined how ketamine, a promising depression treatment, affects different people’s brains in different ways. Rather than averaging brain scans across all participants, researchers looked at individual differences and found that each person showed unique patterns of brain activity changes. The research suggests that personalized approaches to ketamine treatment, based on individual brain responses, could help identify which patients would benefit most from the therapy.

Background

Ketamine has emerged as a promising therapy for treatment-resistant depression, but inter-individual variability in response to ketamine is not well understood. Previous studies have typically averaged brain responses across individuals, potentially masking important individual differences in how ketamine affects the brain.

Objective

To investigate whether individuals show distinct behavioral and neural responses to acute ketamine administration using a multi-dimensional data-driven approach, and to relate these responses to ketamine’s molecular mechanisms involving SST and PVALB GABAergic interneurons.

Results

Ketamine produced multi-dimensional neural and behavioral effects reflecting robust inter-individual variability. The principal neural gradient matched somatostatin and parvalbumin cortical gene expression patterns, while the mean effect did not. Individual symptom variation mapped onto distinct neural gradients resolvable at the single-subject level.

Conclusion

Individual behavioral and neural variation in response to ketamine is substantial and should be considered in treatment selection. These findings support the development of individually precise pharmacological biomarkers for psychiatric treatment.
  • Published in:eLife,
  • Study Type:Clinical Trial,
  • Source: PMC11023699, PMID: 38629811
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