Recent findings published in the Journal of Psychopharmacology have shown a link between the size of the hippocampus and the rapid antidepressant effects of ketamine, a glutamate-based anesthetic drug.

Previous studies suggest a relationship between depression and abnormal functioning of glutamate, a neurotransmitter in the brain. However, the research team noted that many traditional antidepressants are not glutamate-based.

According to Chadi G. Abdallah, corresponding author, treatment-resistant depression is associated with shrinking of the hippocampus—a brain structure critical to learning and memory.

“Smaller hippocampal volume is found in treatment-resistant depression (TRD) patients and has been consistently associated with a poor response to traditional antidepressants,” said Abdallah.

The study, conducted at the Baylor College of Medicine, is believed to be the first of its kind. The use of ketamine as an antidepressant is a fairly recent phenomenon, and research has not previously explored the relationship between ketamine and hippocampal volume.

Conducted at the Baylor College of Medicine, the study examined 24 patients with Major Depressive Disorder (MDD) who were at the time free of medication and experiencing a major depressive episode as defined by the DSM-IV TR. Participants received an infusion of either ketamine or midazolam, another glutamate-based anesthetic drug. 24 hours prior to the infusion, each participant was given an MRI to determine hippocampal volume.

The team found that participants with smaller hippocampal volume, particularly in the left hippocampus, tended to respond better to the ketamine treatment than those with larger hippocampal volume. No significant link was found regarding midazolam, the other drug examined.

Though this type of research is in its infancy, the findings may be significant for individuals with treatment-resistant depression. Previous research has shown that patients with smaller hippocampal volume respond poorly to traditional antidepressants, but scientists may be able to find a new solution in glutamate-based medications.

“While the reader should interpret these preliminary data with extreme caution, it is an intriguing observation that . . . raise[s] an important question regarding . . . ketamine and . . . hippocampal volume,” said Abdallah.