Brain opioid responses altered in major depressive disorder

NEW YORK - The brain's endogenous opioid activity in response to social acceptance and rejection is altered in individuals with major depressive disorder (MDD), according to results of a PET study.

"These findings suggest that the recurrence and maintenance of MDD may be influenced by the brain's opioid response (or lack thereof) to positive and negative social events," Dr. David T. Hsu from Stony Brook University in Stony Brook, New York, told Reuters Health by email. "Further research is needed to discover what current or novel treatments may help boost the response of the brain's natural opioid system during these types of events."

Recent studies in healthy volunteers have shown that social rejection activates the mu-opioid receptor system in a pattern similar to that during physical pain, suggesting that emotional "hurt" during rejection is regulated by opioid pathways for physical pain.

Dr. Hsu and colleagues examined the function of the mu-opioid receptor (MOR) system in response to social rejection and acceptance in 17 patients with MDD, compared with a matched sample of 18 healthy controls.

During rejection, both controls and patients reported feeling sadder and more rejected, and during acceptance, both groups reported feeling happier and more accepted, the team reports online January 20 in Molecular Psychiatry.

During rejection, healthy controls showed activation of the MOR in the right nucleus accumbens, left and right amygdala, midline thalamus, and periaqueductal gray, but MDD patients showed no such activation. In fact, MDD patients showed MOR deactivation in the left and right amygdala that was not present in controls.

During acceptance, healthy controls had significant MOR activation in the right anterior insula and left amygdala, and MDD patients had significant MOR activation in the midline thalamus. Healthy controls also had significant MOR deactivation in the midline thalamus and subgenual anterior cingulate cortex (sgACC), whereas MDD patients had significant deactivation in the left nucleus accumbens.

Ego Resiliency ratings were higher in healthy controls than in MDD patients and were positively correlated with MOR activation during rejection, but the two groups showed no correlation between Ego Resiliency and MOR activation during acceptance.

"The positive relationship between Ego Resiliency and MOR activation in healthy controls suggests that MOR activation during rejection is protective or adaptive," the researchers say.

"Sad and rejected" ratings correlated negatively with MOR activation in the pregenual anterior cingulate cortex in healthy controls, but not in MDD patients. Similarly, increased desire for social interaction correlated positively with MOR activation in the left nucleus accumbens following acceptance in healthy controls, but not in MDD patients.

"Perhaps the most surprising result was that patients with MDD were still able to feel 'happy' and 'accepted' during social acceptance in the laboratory setting," Dr. Hsu said. "This was unexpected since MDD patients typically display anhedonia. However, we found that this positive feeling was short-lived, which may be explained by differences in opioid release during acceptance compared to healthy controls."

"The brain's opioid system may help an individual feel better after negative social interactions, and sustain good feelings after positive social interactions," Dr. Hsu concluded. "Of course everyone responds differently to their social environment, which is why I am currently investigating how individual personality traits and gene variations influence the brain's ability to release opioids during rejection and acceptance."

Dr. Niall Murphy from the University of California, Los Angeles, who has studied the significance of opioid activity in rewarded behaviors, said research by other groups is "identifying polymorphisms in the mu opioid receptor linked to sensitivity to social rejection and the studies in the current paper lend an important and complimentary perspective to this area of research."

"There is a growing consensus that changes in endogenous opioid transmission underlie sophisticated cognitive-affective states, behaviors, and psychological constructs," Dr. Murphy, who was not involved in the new research, told Reuters Health by email.

"These opioid fluxes share much with more basic affective states such as pleasure and pain. This field is moving at a good clip, and we are drawing closer to understanding how sophisticated psychological constructs such as rejection and acceptance are coded neurochemically in the brain."


Mol Psychiatry 2015.

References: Reuters Health
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