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Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression.

ABSTRACT: Buprenorphine is currently being studied for treatment-resistant depression because of its rapid effect, relative safety, and unique pharmacodynamics. To understand the neural impact of buprenorphine in depression, we examined acute limbic and reward circuit changes during an intervention with low-dose buprenorphine augmentation pharmacotherapy. Mid and late-life adults with major depression (N?=?31) who did not completely respond to an adequate trial of venlafaxine were randomized to augmentation with low-dose buprenorphine or matching placebo. We investigated early neural changes using functional magnetic resonance imaging (fMRI) from pre-randomization to 3?weeks using both an emotional reactivity task and a gambling task. We tested if: 1) there were significant neural changes acutely per intervention group, and 2) if acute neural changes were associated with depressive symptom change over 8?weeks using both the total score and the dysphoria subscale of the Montgomery Asberg Depression Rating Scale. Participants in both the buprenorphine and placebo groups showed similar changes in depressive symptoms. Neither the emotional reactivity nor gambling task resulted in significant neural activation changes from pre-randomization to 3-weeks. In both groups, increases in rostral anterior cingulate (rACC) and ventromedial prefrontal cortex (vmPFC) activation during the emotional reactivity task were associated with overall symptom improvement. In the buprenorphine but not the placebo group, increased activation in left anterior insula (aINS) and bilateral middle frontal gyrus (MFG) was associated with improvement on the dysphoria subscale. Activation changes in the reward task were not associated with buprenorphine. This is the first study to show an association between acute neural changes during emotion reactivity and changes in depression severity with buprenorphine treatment.

SUBMITTER: Lin C

PROVIDER: S-EPMC6356006 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression.

Lin Chemin C Karim Helmet T HT Pecina Marta M Aizenstein Howard J HJ Lenze Eric J EJ Blumberger Daniel M DM Mulsant Benoit H BH Kharasch Evan D ED Reynolds Iii Charles F CF Karp Jordan F JF

NeuroImage. Clinical 20190122

Buprenorphine is currently being studied for treatment-resistant depression because of its rapid effect, relative safety, and unique pharmacodynamics. To understand the neural impact of buprenorphine in depression, we examined acute limbic and reward circuit changes during an intervention with low-dose buprenorphine augmentation pharmacotherapy. Mid and late-life adults with major depression (N = 31) who did not completely respond to an adequate trial of venlafaxine were randomized to augmentati ...[more]

PMID: 30685701

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Project description:ImportanceMajor depressive disorder (MDD) is associated with deficits in representing reward prediction errors (RPEs), which are the difference between experienced and predicted reward. Reward prediction errors underlie learning of values in reinforcement learning models, are represented by phasic dopamine release, and are known to affect momentary mood.ObjectiveTo combine functional neuroimaging, computational modeling, and smartphone-based large-scale data collection to test, in the absence of learning-related concerns, the hypothesis that depression attenuates the impact of RPEs.Design, setting, and participantsFunctional magnetic resonance imaging (fMRI) data were collected on 32 individuals with moderate MDD and 20 control participants who performed a probabilistic reward task. A risky decision task with repeated happiness ratings as a measure of momentary mood was also tested in the laboratory in 74 participants and with a smartphone-based platform in 1833 participants. The study was conducted from November 20, 2012, to February 17, 2015.Main outcomes and measuresBlood oxygen level-dependent activity was measured in ventral striatum, a dopamine target area known to represent RPEs. Momentary mood was measured during risky decision making.ResultsOf the 52 fMRI participants (mean [SD] age, 34.0 [9.1] years), 30 (58%) were women and 32 had MDD. Of the 74 participants in the laboratory risky decision task (mean age, 34.2 [10.3] years), 44 (59%) were women and 54 had MDD. Of the smartphone group, 543 (30%) had a depression history and 1290 (70%) had no depression history; 918 (50%) were women, and 593 (32%) were younger than 30 years. Contrary to previous results in reinforcement learning tasks, individuals with moderate depression showed intact RPE signals in ventral striatum (z = 3.16; P = .002) that did not differ significantly from controls (z = 0.91; P = .36). Symptom severity correlated with baseline mood parameters in laboratory (ρ = -0.54; P < 1 × 10-6) and smartphone (ρ = -0.30; P < 1 × 10-39) data. However, participants with depression showed an intact association between RPEs and happiness in a computational model of momentary mood dynamics (z = 4.55; P < .001) that was not attenuated compared with controls (z = -0.42; P = .67).Conclusions and relevanceThe neural and emotional impact of RPEs is intact in major depression. These results suggest that depression does not affect the expression of dopaminergic RPEs and that attenuated RPEs in previous reports may reflect downstream effects more closely related to aberrant behavior. The correlation between symptom severity and baseline mood parameters supports an association between depression and momentary mood fluctuations during cognitive tasks. These results demonstrate a potential for smartphones in large-scale computational phenotyping, which is a goal for computational psychiatry.

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Dataset Information

Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression.

Publications

Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression.

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