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Cortisol awakening response and cerebral serotonin transporter binding
NRM2010 Abstracts – Oral Presentations
S46
Oral Presentation No.: 31
Synaptic Imaging 3
Cortisol awakening response and cerebral serotonin transporter binding Vibe G. Frokjaera, David Erritzoea, Peter Jensena, Jacob Madsenb, William Baaréc, Gitte M. Knudsena a
Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit, Copenhagen University Hospital, Denmark b PET and Cyclotron Unit, Copenhagen University Hospital, Denmark c Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark
Background: Stress sensitivity and serotonergic neurotransmission seem to interact, e.g. in relation to vulnerability for mood disorders. In particular, an increased physiological stress response is genetically linked to the serotonin system through the low expressing s-variant of the 5-HTLPR polymorphism in the promoter region of the serotonin transporter (SERT) gene. Physiological stress activates the hypothalamic– pituitary–adrenal (HPA) axis and leads to cortisol excretion. The HPA-axis activity can be characterized by the cortisol rise following wakening; the cortisol awakening response. In this study we investigated whether HPA-axis activity is associated with cerebral serotonin transporter binding and whether this association might be modified by the s and l genotype of the SERT promoter. Methods: Thirty-two healthy volunteers (mean age 35 ± 20, range 19–81 years, 7 women) underwent serotonin transporter imaging with C[DASB]-PET (positron emission tomography) and performed home-sampling of the cortisol awakening response (CAR) by collecting serial saliva cortisol measures at wakening and every 15 min for the subsequent hour (5 samples). CAR was described by two variables: 1) area under the curve (AUC) with respect to ground (AUCg) that emphasizes the magnitude and thus primarily represents the total hormonal output, and 2) AUC with respect to increase (AUCi) that emphasizes changes over time and thus represents more the HPA-axis reactivity. We tested whether CAR predicted neocortical, pallidostriatal, or frontal SERT binding in a multiple linear regression model with adjustment for age. Interactions between CAR measures and s-allele carrier/non-carrier status were tested by entering AUCg × status and AUCi × status, respectively, in the regression model. Further, we tested if correction for seasonality, s-allele carrier/non-carrier status and Openness personality score contributed significantly in predicting SERT binding or changed the association between CAR and SERT binding. 11
Results: We found, that the stress reactivity component of CAR (AUCi) correlated positively with frontal SERT, when correcting for age (p = 0.02) and also tended to correlate positively with pallidostriatal SERT (p = 0.07). On the other hand, the total cortisol output component (AUCg) correlated positively with pallidostriatal SERT when correcting for age (p = 0.04), whereas it did not correlate significantly with frontal SERT (p = 0.10). No significant interaction between CAR variables and the s-allele carrier/non-carrier status in predicting SERT binding was present. Also, no significant main effect of s-allele carrier/non-carrier status on SERT binding could be demonstrated. When adjusting for insignificant effects of seasonality, s-allele carrier/non-carrier status, or Openness personality score the correlation between frontal SERT binding and AUCi remained practically unchanged while the correlation between pallidostriatal SERT and AUCg became borderline significant. Conclusion: Our findings support, that high SERT binding in frontal regions is associated with larger HPA-axis reactivity in mentally healthy individuals. Also, pallidostriatal SERT seemed to be positively associated with both total cortisol output and reactivity of the HPA-axis. Even though an association between CAR and the low-expressing variant of the SERT promoter gene is well documented, our data suggests that this genotype does not modify the association between cerebral SERT binding and CAR in mentally healthy individuals. doi:10.1016/j.neuroimage.2010.04.227
S46
Oral Presentation No.: 31
Synaptic Imaging 3
Cortisol awakening response and cerebral serotonin transporter binding Vibe G. Frokjaera, David Erritzoea, Peter Jensena, Jacob Madsenb, William Baaréc, Gitte M. Knudsena a
Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit, Copenhagen University Hospital, Denmark b PET and Cyclotron Unit, Copenhagen University Hospital, Denmark c Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark
Background: Stress sensitivity and serotonergic neurotransmission seem to interact, e.g. in relation to vulnerability for mood disorders. In particular, an increased physiological stress response is genetically linked to the serotonin system through the low expressing s-variant of the 5-HTLPR polymorphism in the promoter region of the serotonin transporter (SERT) gene. Physiological stress activates the hypothalamic– pituitary–adrenal (HPA) axis and leads to cortisol excretion. The HPA-axis activity can be characterized by the cortisol rise following wakening; the cortisol awakening response. In this study we investigated whether HPA-axis activity is associated with cerebral serotonin transporter binding and whether this association might be modified by the s and l genotype of the SERT promoter. Methods: Thirty-two healthy volunteers (mean age 35 ± 20, range 19–81 years, 7 women) underwent serotonin transporter imaging with C[DASB]-PET (positron emission tomography) and performed home-sampling of the cortisol awakening response (CAR) by collecting serial saliva cortisol measures at wakening and every 15 min for the subsequent hour (5 samples). CAR was described by two variables: 1) area under the curve (AUC) with respect to ground (AUCg) that emphasizes the magnitude and thus primarily represents the total hormonal output, and 2) AUC with respect to increase (AUCi) that emphasizes changes over time and thus represents more the HPA-axis reactivity. We tested whether CAR predicted neocortical, pallidostriatal, or frontal SERT binding in a multiple linear regression model with adjustment for age. Interactions between CAR measures and s-allele carrier/non-carrier status were tested by entering AUCg × status and AUCi × status, respectively, in the regression model. Further, we tested if correction for seasonality, s-allele carrier/non-carrier status and Openness personality score contributed significantly in predicting SERT binding or changed the association between CAR and SERT binding. 11
Results: We found, that the stress reactivity component of CAR (AUCi) correlated positively with frontal SERT, when correcting for age (p = 0.02) and also tended to correlate positively with pallidostriatal SERT (p = 0.07). On the other hand, the total cortisol output component (AUCg) correlated positively with pallidostriatal SERT when correcting for age (p = 0.04), whereas it did not correlate significantly with frontal SERT (p = 0.10). No significant interaction between CAR variables and the s-allele carrier/non-carrier status in predicting SERT binding was present. Also, no significant main effect of s-allele carrier/non-carrier status on SERT binding could be demonstrated. When adjusting for insignificant effects of seasonality, s-allele carrier/non-carrier status, or Openness personality score the correlation between frontal SERT binding and AUCi remained practically unchanged while the correlation between pallidostriatal SERT and AUCg became borderline significant. Conclusion: Our findings support, that high SERT binding in frontal regions is associated with larger HPA-axis reactivity in mentally healthy individuals. Also, pallidostriatal SERT seemed to be positively associated with both total cortisol output and reactivity of the HPA-axis. Even though an association between CAR and the low-expressing variant of the SERT promoter gene is well documented, our data suggests that this genotype does not modify the association between cerebral SERT binding and CAR in mentally healthy individuals. doi:10.1016/j.neuroimage.2010.04.227