Ketamine produces wide variety of responses in the brain, researchers find

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"Since Yale researchers first observed the ability of the anesthetic ketamine to dramatically improve symptoms in many patients with treatment-resistant depression more than two decades ago, the drug has provided a powerful new therapeutic option for mental health professionals.

However, only 65% of patients treated with ketamine respond to therapy and a new Yale-led study published April 17 in the journal eLife helps explain why.

Using functional magnetic resonance imaging (fMRI), researchers found that ketamine produces a variety of different response patterns in the brains of individuals, an observation that challenges the widely held assumption that treatments for mental health conditions produce the same effect in all people. ...
the different ways that ketamine affects the brain can be related to patterns of gene expression, a finding that might one day help predict who is most likely to respond to ketamine treatment. ...
In fact, they found that ketamine produced many more individually distinct “functional connectivity signatures” than has been observed in studies on the effects of psilocybin and LSD, the researchers report. ..."

From the abstract:

"Background:

Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine’s molecular mechanisms connect to its neural and behavioral effects.

Methods:

We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets.

Results:

We found that:

(i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability;

(ii) ketamine’s data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and

(iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level.

Conclusions:

These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry."

Ketamine produces wide variety of responses in the brain, researchers find | YaleNews A new Yale-led study explains why only 65% of patients treated with ketamine respond to therapy.

Ketamine induces multiple individually distinct whole-brain functional connectivity signatures (open access)

Figure 6 with 4 supplements. Individual variation in ketamine-induced neuro-behavioral changes.