Functional Brain Imaging and Antidepressant Response

Peter ForsterBasic Science, Testing, Treatments of Depression

One of the most exciting initiatives currently in the important area of  the treatment of depression is the International Study to Predict Optimized Treatment in Depression (iSPOT-D). This large multi-center initiative is based on a private industry and academic partnership that is designed to both identify best practices in the treatment of depression and also commercialize them.

The most recent publication from this group looks at the use of functional magnetic resonance imaging to predict treatment response in patients with major depression.

The study looked at 80 patients with major depression and 34 matched controls and performed functional magnetic resonance imaging during the completion of three tasks that assessed separate core cognitive functions: response inhibition, selective attention, and selective working memory updating. After the initial imaging, the patients were randomized to either citalopram, sertraline, or venlafaxine (two serotonin specific reuptake inhibitors and one serotonin and norepinephrine reuptake inhibitor). Functional magnetic resonance imaging scans were repeated after eight weeks of treatment.

The study found that there was an overall predictor of response to any of the antidepressants: greater dorsolateral prefrontal cortex activation during tasks designed to test the ability of the patient to inhibit responses.

Recall that the prefrontal cortex plays a largely inhibitory response. In other words it is designed to reduce reflexive action. In this study greater activation of the prefrontal cortex when patients were tasked with something that required inhibiting action was associated with a better response to an antidepressant.

You may recall that the dorsolateral prefrontal cortex is the same area that is stimulated with transcranial magnetic stimulation. This study then showed that medications work best in those patients whose dorsolateral prefrontal cortex was more active, by implication those patients with less activation might’ve responded better to TMS.

An additional finding was that inferior parietal activation distinguished those who would be more likely to respond to SSRIs and SNRIs. Those responding to SSRIs showed greater activation prior to treatment in the inferior parietal region than those who did not respond to an SSRI and the SNRI group showed the opposite pattern. This finding adds to an interesting literature suggesting that we may soon be able to predict who is more likely to respond to one class of antidepressant or another.


Gyurak A, Patenaude B, Korgaonkar MS, Grieve SM, Williams LM, Etkin A. Frontoparietal Activation During Response Inhibition Predicts Remission to Antidepressants in Patients With Major Depression. Biol Psychiatry. 2016 Feb 15;79(4):274-81. doi: 10.1016/j.biopsych.2015.02.037. Epub 2015 Mar 27. PubMed PMID: 25891220.