Relationships Between Changes in Sustained Fronto-Striatal Connectivity and Positive Affect in Major Depression Resulting From Antidepressant Treatment

Abstract

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 over time of this network is unknown. Accordingly, we 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, we 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 prior to, and after 2 months of antidepressant treatment. 14 healthy control subjects were scanned over the same interval. Results After 2 months of treatment, self-reported positive affect increased. Those patients demonstrating the largest increases in sustained nucleus accumbens activity over the 2 months were those demonstrating the largest increases in positive affect. In addition, those patients demonstrating the largest increases in sustained fronto-striatal connectivity were also those demonstrating the largest increases in positive affect when controlling for negative affect. Healthy controls showed none of these associations. Conclusions Treatment induced changes 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.

Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties

“…Therefore, we can only speculate that a more normative pattern of pre-treatment caudate-dACC connectivity may be associated with larger and global clinical improvement. Further highlighting the role of these neural pathways in clinical course, treatment-induced normalization of fronto-striatal functional connectivity was found to positively correlate with increases in positive affect (Heller et al 2013). Critically, clinical improvement was achieved through either Venlafaxine or Fluoxetine, suggesting that the mechanism of action fostering improvements in positive affect and fronto-striatal connectivity did not differ between the two antidepressants (Heller et al 2013).…”

“…Further highlighting the role of these neural pathways in clinical course, treatment-induced normalization of fronto-striatal functional connectivity was found to positively correlate with increases in positive affect (Heller et al 2013). Critically, clinical improvement was achieved through either Venlafaxine or Fluoxetine, suggesting that the mechanism of action fostering improvements in positive affect and fronto-striatal connectivity did not differ between the two antidepressants (Heller et al 2013). Similarly, a recent meta-analysis indicated that increased pre-treatment ACC and striatum activation is a robust predictor of positive response to both pharmacological and behavioral treatment in MDD (Fu et al 2013).…”

Axonal myelin increase in the callosal genu in depression but not schizophrenia

“…SZ, Schizophrenia; MDD, major depressive disorder. subcortical structures in MDD (Heller et al 2013;Strigo et al 2013). While these increased levels of connectivity are observed in detailed studies, it is possible that the dominant negative symptoms of MDD mask clinical indications of greater inter-hemispheric connectivity.…”

Neural predictors of depression symptom course

“…Among others, these include age of onset of initial depressive episode, number of previous depressive episodes [62], duration of depressive illness [63,64], existence of early childhood trauma [65], and features of emotional dynamics [66][67][68][69], etc. While some studies have indeed controlled for (or specifically examined) such features, it is possible that such individual differences will account for variability (and lack of replication) across studies and help the field better understand the course of the illness.…”