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Intrinsic functional connectivity in late-life depression: Trajectories over the course of pharmacotherapy in remitters and non-remitters
Karim HT, Andreescu C, Tudorascu D, Smagula SF, Butters MA, Karp JF, Reynolds C and Aizenstein HJ
Molecular Psychiatry, Published online 2016

Previous studies in late-life depression (LLD) have found that patients have altered intrinsic functional connectivity in the dorsal default mode network (DMN) and executive control network (ECN). Researchers in the Department of Psychiatry's late life depression program investigate connectivity differences across a treatment trial among LLD patients as a function of remission status. 

A total of 37 patients with late life depression were enrolled into a 12-week trial of venlafaxine and underwent five functional magnetic resonance imaging resting state scans during treatment. Research participants had no history of drug abuse, psychosis, dementia/neurodegenerative diseases or medical conditions with known effects on mood. The researchers investigated whether there were differences in three networks: DMN, ECN and anterior salience network connectivity, as well as a whole brain centrality measure (eigenvector centrality). 

Drs. Howard Aizenstein, Carmen Andreescu and Bioengineering PhD candidate, Helmet Karim, along with their colleagues found that remitters showed increases in ECN connectivity in the right precentral gyrus and decreases in DMN connectivity in the right inferior frontal gyrus and supramarginal gyrus. The ECN and DMN had regions (middle temporal gyrus and bilateral middle/inferior temporal/fusiform gyrus, respectively) that showed reversed effects (decreased ECN and increased DMN, respectively). Early changes in functional connectivity can occur after initial medication exposure. In this case the changes were seen 12-hours after initial exposure to the antidepressant, suggesting an early marker of antidepressant (monoaminergic) engagement.

This study offers new data indicating that functional connectivity changes differ depending on treatment response, and can occur shortly after exposure to antidepressant medication. The investigators are currently conducting a randomized clinical trial to investigate how this functional signal of monoaminergic engagement can predict treatment response, and ultimately guide personalized treatment of older adults with late-life depression.

Contributors:
Helmet T. Karim, PhD (Department of Bioengineering, University of Pittsburgh)

Carmen Andreescu, MD, S F Smagula, Meryl A. Butters, PhD, Jordan F. Karp, MD, Charles F. Reynolds, III, MD and Howard J. Aizenstein, MD, PhD (Department of Psychiatry, University of Pittsburgh School of Medicine)

Dana L. Tudorascu, PhD (Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh)

This article appears in the journal Molecular Psychiatry.  Click here to view the abstract.