Relationships between changes in sustained fronto-striatal connectivity and positive affect in major depression resulting from antidepressant treatment.

Objective: Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity. or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. Method: Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients before and after 2 months of antidepressant treatment. Over the same interval, 14 healthy comparison. subjects underwent scanning as well. Results: After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those Who demonstrated the largest increases in positive affect when controlling for negative affect. None of these associations were observed in healthy comparison subjects. Conclusions: Treatment-induced change in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect. (Am J Psychiatry 2073; 170:197-206)