Ketamine induces multiple individually distinct whole-brain functional connectivity signatures

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Ketamine shows promise for treatment-resistant depression.
• Individual response variability to ketamine remains poorly understood.
• The link between ketamine's molecular mechanisms and its neural/behavioral effects is unclear.

Purpose of the Study:

• To investigate inter-individual variability in ketamine's neural and behavioral effects.
• To explore the relationship between ketamine's effects, gene expression, and neural connectivity.
• To identify potential biomarkers for predicting ketamine response.

Main Methods:

• Single-blind, placebo-controlled study with 40 healthy participants.
• Administered acute ketamine via bolus and continuous infusion.
• Quantified resting-state functional connectivity and related it to symptom variation and gene expression.

Main Results:

• Ketamine's neural and behavioral effects are multi-dimensional with significant individual variability.
• Data-driven neural gradients correlated with somatostatin (SST) and parvalbumin (PVALB) gene expression.
• Individual symptom variations mapped to distinct, subject-level neural gradients.

Conclusions:

• Individual neural and behavioral variations are crucial for understanding ketamine response.
• Findings support the development of personalized pharmacological biomarkers for psychiatric treatment selection.