Last week I discussed two reviews of neuroimaging studies attempting to untangle the biology of depression by studying activity of specific brain regions and neurotransmitter-associated proteins as well as at the prospect of identifying biomarkers to predict treatment response.
In addition to identifying patients who would respond to specific treatments, biomarkers have been sought to diagnose depression, to identify those at risk for whom prophylactic treatment might be appropriate, and to identify biological components or dimensions of depression.
Three weeks ago I looked at neuropharmacological aspects of the neurobiology of depression. It’s time to fill in the picture with a discussion of neuroimaging research from two recent reviews. Manpreet Singh and Ian Gotlib of Stanford summarize findings from structural and functional MRI studies, and Jeffrey Meyer from the University of Toronto discusses PET, SPECT, and proton MRI studies, all of which use radiolabeled molecules to look at particular neurotransmitters or receptors. Unsurprisingly, the results are very complex and sometimes contradictory, with no clear picture emerging, but, as we know, depression is a clinical syndrome which may have multiple, possibly overlapping, biologies.
When I wrote two weeks agoabout depression, two genes stood out--theserotonin transporter gene and two associated with catecholamine metabolism. Interestingly, variants in these and related genes turn out to be associated with placebo responses. Thatled me to wonder if an overlap between the mechanisms antidepressant effects and the biology of placebo responses might account for the high placebo response rates in clinical trials of antidepressant medication and the notorious difficulty of demonstrating efficacy of antidepressants in randomized controlled trials.
For a first take on the question, I will look at fascinating review of genetics and placebo effects byKathyrn Hall, Joseph Loscalzo, and Ted Kaptchuk of the Program in Placebo Studies and Therapeutic Encounter at Beth Israel Deaconess Medical Center in Boston. I will focus mainly on antidepressant placebo responses.
The authors note that almost all modern randomized controlled trials lack a no-treatment control, which makes it d...
These academic pieces pull together research from several disciplines to generate a picture of what goes on in patients’—and more sketchily, doctors’—brains. The science encompasses neurophysiology, pharmacology, experimental psychology, and neuroimaging, and includes several neural circuits and transmitter systems—pain pathways involving endogenous opioids, the dopamine reward system, the amygdala, and descending cholecystokinin tracts which antagonize the analgesic effects of µ-opiods. (A side note: cholecystokinin can also induce panic-like symptoms and is used to screen potential anti-anxiety drugs.)