"Expectancy-Mood Neural Dynamics Predict Mechanisms of Short- and Long-Term Antidepressant Placebo Effects".

Objective: Acute experimental models of antidepressant placebo effects suggest that expectancies, encoded within the salience network (SN), are reinforced by sensory evidence and mood fluctuations. However, whether these dynamics extend to longer timescales remains unknown. To answer this question, we investigated how SN and default mode network (DMN) functional connectivity during the processing of antidepressant expectancies facilitates the shift from salience attribution to contextual cues in the SN to belief-induced mood responses in the DMN, both acutely and long-term.

μ Opioid Antagonist Naltrexone Partially Abolishes the Antidepressant Placebo Effect and Reduces Orbitofrontal Cortex Encoding of Reinforcement.

Background: Like placebo analgesia, the antidepressant placebo effect appears to involve cortical and subcortical endogenous opioid signaling, yet the mechanism through which opioid release affects mood remains unclear. The orbitofrontal cortex (OFC)-which integrates various attributes of a stimulus to predict associated outcomes-has been implicated in placebo effects and is rich in μ opioid receptors. We hypothesized that naltrexone blockade of μ opioid receptors would blunt OFC-dependent antidepressant placebo effects.

Expectancy Modulation of Opioid Neurotransmission.

Expectancies are powerful modulators of cognitive and emotional experiences, as well as the neurobiological responses linked to these processes. In medicine, placebo effects are a clear example of how expectancies activate opioid neurotransmission in a treatment context, leading to the experience of analgesia and the improvement of emotional states, among other symptoms. Molecular neuroimaging techniques using positron emission tomography (PET) and the selective μ-opioid receptor tracer [C]carfentanil have significantly contributed to our understanding of the neurobiological systems involved in the formation of placebo effects.

Striatal dopamine D2/3 receptor-mediated neurotransmission in major depression: Implications for anhedonia, anxiety and treatment response.

Dopamine (DA) neurotransmission within the brain's reward circuit has been implicated in the pathophysiology of depression and in both, cognitive and pharmacological mechanisms of treatment response. Still, a direct relationship between measures of DA neurotransmission and reward-related deficits in patients with depression has not been demonstrated. To gain insight into the symptom-specific alterations in the DA system in patients with depression, we used positron emission tomography (PET) and the D receptor-selective radiotracer [C]raclopride in twenty-three non-smoking un-medicated Major Depressive Disorder (MDD) patients and sixteen healthy controls (HC).