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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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Extracted data from VOIs (red outlines) correlated with trait resiliency and state changes. MOR activation during Rejection correlated with Ego Resiliency in the (a) amygdala (b) PAG, and (c) sgACC, suggesting that high-resilient individuals are more capable of MOR activation in these regions during rejection. (d) Increased ratings for “sad and rejected” were negatively correlated with MOR activation in the pgACC (i.e., subjects who felt less “sad and rejected” had greater MOR activation during Rejection). (e) During Acceptance, increased ratings in the desire for social interaction were positively correlated with MOR activation in the left ventral striatum.
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Figure 3: Extracted data from VOIs (red outlines) correlated with trait resiliency and state changes. MOR activation during Rejection correlated with Ego Resiliency in the (a) amygdala (b) PAG, and (c) sgACC, suggesting that high-resilient individuals are more capable of MOR activation in these regions during rejection. (d) Increased ratings for “sad and rejected” were negatively correlated with MOR activation in the pgACC (i.e., subjects who felt less “sad and rejected” had greater MOR activation during Rejection). (e) During Acceptance, increased ratings in the desire for social interaction were positively correlated with MOR activation in the left ventral striatum.

Mentions: During Rejection compared to matched Baseline block, subjects reported feeling more “sad and rejected” (t16 = 5.11, p < 0.001) and less “happy and accepted” (t16 = 6.03, p < 0.001, Fig. 1c). Significant MOR activation was found in the left and right amygdala, right ventral striatum, midline thalamus, and PAG (Fig. 2a, Table 1). No significant MOR deactivations were found. The trait Ego Resiliency was positively correlated with MOR activation during Rejection in the amygdala (left, r = 0.48, p = 0.04; right, r = 0.54, p = 0.02), PAG (r = 0.66, p = 0.003), and sgACC (r = 0.65, p = 0.003) (Fig. 3a–c). Increased ratings for “sad and rejected” was negatively correlated with MOR activation in the pgACC (r = −0.73, p < 0.001, Fig. 3d). Subjects reported a decreased desire for social interaction following Rejection compared to Baseline (t16 = 2.14, p = 0.048), however this change was not significantly correlated with MOR activation in the VOIs. During Acceptance compared to matched Baseline block, subjects reported feeling more “happy and accepted” (t16 = 3.71, p = 0.002), with no change in “sad and rejected” (t16 = 0.87, p = 0.40) (Fig. 1d). Significant MOR activation was found in the right anterior insula and left amygdala (Fig 2b, Table 1), whereas significant deactivation was found in the midline thalamus and sgACC (Fig. 2b, Table 1). Neither Ego Resiliency nor scores for “happy and accepted” were significantly correlated with MOR activation in the VOIs. Subjects reported an increased desire for social interaction following Acceptance compared to Baseline (t15 = 2.91, p = 0.01), and this change was positively correlated with MOR activation in the left ventral striatum (r = 0.60, p = 0.01, Fig. 3e).


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)

Extracted data from VOIs (red outlines) correlated with trait resiliency and state changes. MOR activation during Rejection correlated with Ego Resiliency in the (a) amygdala (b) PAG, and (c) sgACC, suggesting that high-resilient individuals are more capable of MOR activation in these regions during rejection. (d) Increased ratings for “sad and rejected” were negatively correlated with MOR activation in the pgACC (i.e., subjects who felt less “sad and rejected” had greater MOR activation during Rejection). (e) During Acceptance, increased ratings in the desire for social interaction were positively correlated with MOR activation in the left ventral striatum.
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Related In: Results  -  Collection

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Figure 3: Extracted data from VOIs (red outlines) correlated with trait resiliency and state changes. MOR activation during Rejection correlated with Ego Resiliency in the (a) amygdala (b) PAG, and (c) sgACC, suggesting that high-resilient individuals are more capable of MOR activation in these regions during rejection. (d) Increased ratings for “sad and rejected” were negatively correlated with MOR activation in the pgACC (i.e., subjects who felt less “sad and rejected” had greater MOR activation during Rejection). (e) During Acceptance, increased ratings in the desire for social interaction were positively correlated with MOR activation in the left ventral striatum.
Mentions: During Rejection compared to matched Baseline block, subjects reported feeling more “sad and rejected” (t16 = 5.11, p < 0.001) and less “happy and accepted” (t16 = 6.03, p < 0.001, Fig. 1c). Significant MOR activation was found in the left and right amygdala, right ventral striatum, midline thalamus, and PAG (Fig. 2a, Table 1). No significant MOR deactivations were found. The trait Ego Resiliency was positively correlated with MOR activation during Rejection in the amygdala (left, r = 0.48, p = 0.04; right, r = 0.54, p = 0.02), PAG (r = 0.66, p = 0.003), and sgACC (r = 0.65, p = 0.003) (Fig. 3a–c). Increased ratings for “sad and rejected” was negatively correlated with MOR activation in the pgACC (r = −0.73, p < 0.001, Fig. 3d). Subjects reported a decreased desire for social interaction following Rejection compared to Baseline (t16 = 2.14, p = 0.048), however this change was not significantly correlated with MOR activation in the VOIs. During Acceptance compared to matched Baseline block, subjects reported feeling more “happy and accepted” (t16 = 3.71, p = 0.002), with no change in “sad and rejected” (t16 = 0.87, p = 0.40) (Fig. 1d). Significant MOR activation was found in the right anterior insula and left amygdala (Fig 2b, Table 1), whereas significant deactivation was found in the midline thalamus and sgACC (Fig. 2b, Table 1). Neither Ego Resiliency nor scores for “happy and accepted” were significantly correlated with MOR activation in the VOIs. Subjects reported an increased desire for social interaction following Acceptance compared to Baseline (t15 = 2.91, p = 0.01), and this change was positively correlated with MOR activation in the left ventral striatum (r = 0.60, p = 0.01, Fig. 3e).

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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