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Response of the μ-opioid system to social rejection and acceptance.

Hsu DT, Sanford BJ, Meyers KK, Love TM, Hazlett KE, Wang H, Ni L, Walker SJ, Mickey BJ, Korycinski ST, Koeppe RA, Crocker JK, Langenecker SA, Zubieta JK - Mol. Psychiatry (2013)

Bottom Line: Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus and periaqueductal gray (PAG).In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection.In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, The Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.

ABSTRACT
The endogenous opioid system, which alleviates physical pain, is also known to regulate social distress and reward in animal models. To test this hypothesis in humans (n=18), we used an μ-opioid receptor (MOR) radiotracer to measure changes in MOR availability in vivo with positron emission tomography during social rejection (not being liked by others) and acceptance (being liked by others). Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus and periaqueductal gray (PAG). This pattern of activation is consistent with the hypothesis that the endogenous opioids have a role in reducing the experience of social pain. Greater trait resiliency was positively correlated with MOR activation during rejection in the amygdala, PAG and subgenual anterior cingulate cortex (sgACC), suggesting that MOR activation in these areas is protective or adaptive. In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection. In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC. In the left ventral striatum, MOR activation during acceptance predicted a greater desire for social interaction, suggesting a role for the MOR system in social reward. The ventral striatum, amygdala, midline thalamus, PAG, anterior insula and ACC are rich in MORs and comprise a pathway by which social cues may influence mood and motivation. MOR regulation of this pathway may preserve and promote emotional well being in the social environment.

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Study design and behavioral results. (a) During the scan, the subject is presented with self-selected profiles (left) along with her own profile (right), viewed on a personal computer. The following information is presented in succession: the first line reminds the subject how much she liked this person, the second line reminds the subject that she believed this person would like her, the last line provides feedback that this person did not like her (Rejection shown here) or did like her (Acceptance). After each trial, subjects rate how they feel. (b) Each subject received an intravenous injection of [11C]-labeled carfentanil and completed two scans for examining Rejection and Acceptance blocks, compared with Baseline blocks from the same post-injection time frame. The order of scans 1 and 2, and Rejection and Acceptance, were counterbalanced between subjects using the Latin Squares design to control for potential order effects. (c) Subjects reported feeling more “sad and rejected” during the Rejection block, and (d) more “happy and accepted” during the Acceptance block, compared to matched Baseline blocks (mean ± s.e.m). Consent was obtained by DT Hsu to publish the likenesses in this image.
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Figure 1: Study design and behavioral results. (a) During the scan, the subject is presented with self-selected profiles (left) along with her own profile (right), viewed on a personal computer. The following information is presented in succession: the first line reminds the subject how much she liked this person, the second line reminds the subject that she believed this person would like her, the last line provides feedback that this person did not like her (Rejection shown here) or did like her (Acceptance). After each trial, subjects rate how they feel. (b) Each subject received an intravenous injection of [11C]-labeled carfentanil and completed two scans for examining Rejection and Acceptance blocks, compared with Baseline blocks from the same post-injection time frame. The order of scans 1 and 2, and Rejection and Acceptance, were counterbalanced between subjects using the Latin Squares design to control for potential order effects. (c) Subjects reported feeling more “sad and rejected” during the Rejection block, and (d) more “happy and accepted” during the Acceptance block, compared to matched Baseline blocks (mean ± s.e.m). Consent was obtained by DT Hsu to publish the likenesses in this image.

Mentions: During the PET scan, subjects were presented with their highest-rated profiles along with feedback that they were not liked (Rejection), or liked (Acceptance) (Fig. 1a). Rejection and Acceptance blocks were 24 minutes each and contained 12 unique trials of equal length with varying levels of rejection/acceptance (7 trials “definitely no/yes”, 4 trials “very likely no/yes,” and 1 trial “likely no/yes”). Baseline scans were included to compare MOR BP during the same post-injection time frame (Fig. 1b). Baseline trials contained a similar visual presentation, with grayscale blocks in place of the pictures, and profile information and feedback presented as “N/A”. This task did not involve deception, but subjects were asked to imagine that the profiles and feedback were real (see Supplementary Methods). During each trial subjects reported on a 5-point Likert scale how much they felt sad, rejected, happy, and accepted (order randomized in each trial). Following each block, subjects were given a 4-item questionnaire measuring their current desire for social interaction (see Supplementary Methods). All behavioral responses were obtained using a five-button response box.


Response of the μ-opioid system to social rejection and acceptance.

Hsu DT, Sanford BJ, Meyers KK, Love TM, Hazlett KE, Wang H, Ni L, Walker SJ, Mickey BJ, Korycinski ST, Koeppe RA, Crocker JK, Langenecker SA, Zubieta JK - Mol. Psychiatry (2013)

Study design and behavioral results. (a) During the scan, the subject is presented with self-selected profiles (left) along with her own profile (right), viewed on a personal computer. The following information is presented in succession: the first line reminds the subject how much she liked this person, the second line reminds the subject that she believed this person would like her, the last line provides feedback that this person did not like her (Rejection shown here) or did like her (Acceptance). After each trial, subjects rate how they feel. (b) Each subject received an intravenous injection of [11C]-labeled carfentanil and completed two scans for examining Rejection and Acceptance blocks, compared with Baseline blocks from the same post-injection time frame. The order of scans 1 and 2, and Rejection and Acceptance, were counterbalanced between subjects using the Latin Squares design to control for potential order effects. (c) Subjects reported feeling more “sad and rejected” during the Rejection block, and (d) more “happy and accepted” during the Acceptance block, compared to matched Baseline blocks (mean ± s.e.m). Consent was obtained by DT Hsu to publish the likenesses in this image.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3814222&req=5

Figure 1: Study design and behavioral results. (a) During the scan, the subject is presented with self-selected profiles (left) along with her own profile (right), viewed on a personal computer. The following information is presented in succession: the first line reminds the subject how much she liked this person, the second line reminds the subject that she believed this person would like her, the last line provides feedback that this person did not like her (Rejection shown here) or did like her (Acceptance). After each trial, subjects rate how they feel. (b) Each subject received an intravenous injection of [11C]-labeled carfentanil and completed two scans for examining Rejection and Acceptance blocks, compared with Baseline blocks from the same post-injection time frame. The order of scans 1 and 2, and Rejection and Acceptance, were counterbalanced between subjects using the Latin Squares design to control for potential order effects. (c) Subjects reported feeling more “sad and rejected” during the Rejection block, and (d) more “happy and accepted” during the Acceptance block, compared to matched Baseline blocks (mean ± s.e.m). Consent was obtained by DT Hsu to publish the likenesses in this image.
Mentions: During the PET scan, subjects were presented with their highest-rated profiles along with feedback that they were not liked (Rejection), or liked (Acceptance) (Fig. 1a). Rejection and Acceptance blocks were 24 minutes each and contained 12 unique trials of equal length with varying levels of rejection/acceptance (7 trials “definitely no/yes”, 4 trials “very likely no/yes,” and 1 trial “likely no/yes”). Baseline scans were included to compare MOR BP during the same post-injection time frame (Fig. 1b). Baseline trials contained a similar visual presentation, with grayscale blocks in place of the pictures, and profile information and feedback presented as “N/A”. This task did not involve deception, but subjects were asked to imagine that the profiles and feedback were real (see Supplementary Methods). During each trial subjects reported on a 5-point Likert scale how much they felt sad, rejected, happy, and accepted (order randomized in each trial). Following each block, subjects were given a 4-item questionnaire measuring their current desire for social interaction (see Supplementary Methods). All behavioral responses were obtained using a five-button response box.

Bottom Line: Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus and periaqueductal gray (PAG).In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection.In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, The Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.

ABSTRACT
The endogenous opioid system, which alleviates physical pain, is also known to regulate social distress and reward in animal models. To test this hypothesis in humans (n=18), we used an μ-opioid receptor (MOR) radiotracer to measure changes in MOR availability in vivo with positron emission tomography during social rejection (not being liked by others) and acceptance (being liked by others). Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus and periaqueductal gray (PAG). This pattern of activation is consistent with the hypothesis that the endogenous opioids have a role in reducing the experience of social pain. Greater trait resiliency was positively correlated with MOR activation during rejection in the amygdala, PAG and subgenual anterior cingulate cortex (sgACC), suggesting that MOR activation in these areas is protective or adaptive. In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection. In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC. In the left ventral striatum, MOR activation during acceptance predicted a greater desire for social interaction, suggesting a role for the MOR system in social reward. The ventral striatum, amygdala, midline thalamus, PAG, anterior insula and ACC are rich in MORs and comprise a pathway by which social cues may influence mood and motivation. MOR regulation of this pathway may preserve and promote emotional well being in the social environment.

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