The role of serotonin in the neurocircuitry of negative affective bias: serotonergic modulation of the dorsal medial prefrontal-amygdala 'aversive amplification' circuit - PubMed (original) (raw)

Randomized Controlled Trial

The role of serotonin in the neurocircuitry of negative affective bias: serotonergic modulation of the dorsal medial prefrontal-amygdala 'aversive amplification' circuit

Oliver J Robinson et al. Neuroimage. 2013 Sep.

Abstract

Serotonergic medications can mitigate the negative affective biases in disorders such as depression or anxiety, but the neural mechanism by which this occurs is largely unknown. In line with recent advances demonstrating that negative affective biases may be driven by specific medial prefrontal-amygdala circuitry, we asked whether serotonin manipulation can alter affective processing within a key dorsal medial prefrontal-amygdala circuit: the putative human homologue of the rodent prelimbic-amygdala circuit or 'aversive amplification' circuit. In a double-blind, placebo-controlled crossover pharmaco-fMRI design, subjects (N=19) performed a forced-choice face identification task with word distractors in an fMRI scanner over two separate sessions. On one session subjects received dietary depletion of the serotonin precursor tryptophan while on the other session they received a balanced placebo control diet. Results showed that dorsal medial prefrontal responding was elevated in response to fearful relative to happy faces under depletion but not placebo. This negative bias under depletion was accompanied by a corresponding increase in positive dorsal medial prefrontal-amygdala functional connectivity. We therefore conclude that serotonin depletion engages a prefrontal-amygdala circuit during the processing of fearful relative to happy face stimuli. This same 'aversive amplification' circuit is also engaged during anxiety induced by shock anticipation. As such, serotonergic projections may inhibit engagement of the 'aversive amplification' circuit and dysfunction in this projection may contribute to the negative affective bias in mood and anxiety disorders. These findings thus provide a promising explanation for the role of serotonin and serotonergic medications in the neurocircuitry of negative affective bias.

Published by Elsevier Inc.

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Conflict of interest statement

CONFLICT OF INTEREST

The author(s) declare that, except for income received from the primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. Dr Pine has received compensation for activities related to teaching, editing, and clinical care that pose no conflicts of interest.

Figures

Figure 1

Figure 1. Functional Imaging effects

a) The threat-potentiated dMPFC-amygdala connectivity seen in our prior study (Fear threat vs safe contrast t=3–3.5) (Robinson et al. 2012) shows overlap with the b) treatment × valence interaction in event related activity (t=1.5–2) in our current study. This interaction was driven by c) increased activity in dMPFC for fearful faces under ATD (extracted betas averaged across region of interest for illustration). This was also associated with d) increased dmPFC-amygdala connectivity in the same region for fearful (fear ATD vs BAL PPI contrast t=0.5–1.5) but not e) happy faces (extracted betas averaged across region of interest for illustration). Crosshairs on all images point to peak threat potentiated dMPFC-amygdala coupling from Robinson 2012, numbers represent slices. ATD = acute tryptophan depletion; BAL= balanced placebo; L= left; R=right; dMPFC = dorsal medial prefrontal cortex.

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