Changes in neural reward processing following Amplification of Positivity treatment for depression and anxiety: Preliminary findings from a randomized waitlist controlled trial

Abstract

Positive valence system (PVS) deficits are increasingly recognized as important treatment targets for depression and anxiety. Emerging behavioral treatments designed to upregulate the PVS show initial promise; however, neural mechanisms underlying these approaches remain unknown. This study investigated neural reward-processing-related changes following Amplification of Positivity (AMP)-a treatment designed to enhance positive thinking, emotions and behaviors through positive activity interventions (Clinicaltrials.gov: NCT02330627). Individuals with depression and/or anxiety (N = 29) were randomized to 10 sessions of AMP (n = 16) or waitlist (WL; n = 13). Participants completed a monetary incentive delay task during fMRI at baseline and post-assessment. Hypothesis-driven region of interest (ventral striatum, insula, anterior cingulate) and exploratory whole-brain activation and connectivity analyses evaluated pre-to-post changes for AMP vs. WL when anticipating potential monetary gain or loss. No between-group brain activation changes emerged in regions of interest or whole-brain analyses. Increased neural connectivity from pre-to-post-treatment was observed in AMP vs. WL, including ventral striatum, anterior insula, and anterior cingulate connectivity with prefrontal, limbic, occipital and parietal regions-predominantly during loss anticipation. This preliminary study is the first to examine neural mechanisms of positive activity interventions in depression and anxiety and suggests that AMP may strengthen brain connectivity in reward processing, attention, and emotion regulation networks.

Keywords: Anxiety; Clinical trial; Depression; Positive affect; Reward processing; fMRI.

Conflict of interest statement

Conflict of Interest: Maria Kryza-Lacombe, Nana Pearson, and Jillian Lee Wiggins declare that they have no conflicts of interest. Charles T. Taylor declares that in the past 3 years he has been a paid consultant for Homewood Health, and receives payment for editorial work for UpToDate. Murray B. Stein declares that in the past 3 years he has been a paid consultant for Acadia Pharmaceuticals, Aptinyx, Bionomics, Genentech/Roche, GW Pharma, and Janssen, and receives payment for editorial work for UpToDate and the journals Biological Psychiatry and Depression and Anxiety. Sonja Lyubomirsky declares that in the past 3 years she has been a paid lecturer for the University of Arizona Center for Integrative Medicine and the Laureate Institute for Brain Research.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Figures

Figure 1.. Ventral Striatum Connectivity.

A) Group × Time × Gain vs. Loss interaction predicts left ventral striatum connectivity with the right middle occipital gyrus. B) Group × Time × Loss vs. No Incentive interaction predicts right ventral striatum connectivity with the left cuneus. *p<0.05, ** p<0.01, ^p<0.1, corrected. Error bars represent 95% confidence interval. AMP=treatment group that underwent Amplification of Positivity, WL=waitlist control group that did not undergo an intervention. For this and all figures, brain images represent axial sections (left=left) with threshold set at whole-brain-corrected p<.05.

Figure 2.. Anterior Insula Connectivity.

A) Group × Time × Gain vs. No Incentive interaction predicts left anterior insula connectivity with the right middle frontal gyrus. B) Group × Time × Loss vs. No Incentive interaction predicts right anterior insula connectivity with the right middle occipital gyrus. *p<0.05, ***p<0.001, corrected. Error bars represent 95% confidence interval. AMP=treatment group that underwent Amplification of Positivity, WL=waitlist control group that did not undergo an intervention.

Figure 3.. Anterior Cingulate Cortex Connectivity.

A) Group × Time × Loss vs. No Incentive interaction predicts left anterior cingulate connectivity with the left ventral striatum. B) Group × Time × Loss vs. No Incentive interaction predicts right anterior cingulate connectivity with the right middle frontal gyrus. *p<0.05, ***p<0.001, corrected. Error bars represent 95% confidence interval. AMP=treatment group that underwent Amplification of Positivity, WL=waitlist control group that did not undergo an intervention.