Effects of Early-Life Stress on Serotonin1A Receptors in Juvenile Rhesus Monkeys Measured by Positron Emission Tomography

Spinelli, Simona; Chefer, Svetlana; Carson, Richard E.; Jagoda, Elaine; Lang, Lixin; Heilig, Markus; Barr, Christina S.; Suomi, Stephen J.; Higley, J. Dee; Stein, Elliot A.

doi:10.1016/j.biopsych.2009.12.030

« Previous Next »Biological Psychiatry
Volume 67, Issue 12 , Pages 1146-1153, 15 June 2010

Effects of Early-Life Stress on Serotonin_1A Receptors in Juvenile Rhesus Monkeys Measured by Positron Emission Tomography

Simona Spinelli
- Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Poolesville, Maryland
- Address correspondence to Simona Spinelli, Ph.D., Laboratory for Neurocognitive and Imaging Research, Kennedy Krieger Institute, Johns Hopkins School of Medicine, 716 North Broadway, Baltimore, MD 21205
Svetlana Chefer
- Neuroimaging Research Branch, National Institute on Drug Abuse, Baltimore, Maryland
Richard E. Carson
- PET Center, Department of Radiology, Yale University, New Haven, Connecticut
Elaine Jagoda
- National Institute of Biomedical Imaging and Bioengineering, Bethesda, Maryland
Lixin Lang
- National Institute of Biomedical Imaging and Bioengineering, Bethesda, Maryland
Markus Heilig
- National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
Christina S. Barr
- Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Poolesville, Maryland
Stephen J. Suomi
- Laboratory of Comparative Ethology, National Institute of Child Health and Human Development, Poolesville, Maryland
J. Dee Higley
- Department of Psychology, Brigham Young University, Provo, Utah
Elliot A. Stein
- Neuroimaging Research Branch, National Institute on Drug Abuse, Baltimore, Maryland

Received 31 July 2009; received in revised form 14 December 2009; accepted 26 December 2009. published online 22 February 2010.

Background

Traumatic experiences in early childhood are associated with increased risk for developing mood and anxiety disorders later in life. Low serotonin_1A receptor (5-HT_1AR) density during development has been proposed as a trait-like characteristic leading to increased vulnerability of stress-related neuropsychiatric disorders.

Methods

To assess the relationship between early-life stress and alterations in the serotonin system during development, we used positron emission tomography to measure in vivo 5-HT_1AR density and apparent dissociation constant (K_D^app) in the brain of juvenile Rhesus monkeys exposed to the early-life stress of peer-rearing.

Results

In general, 5-HT_1AR density and K_D^app were decreased in peer-reared compared with control mother-reared animals. However, increase in receptor density was found in the dorsomedial prefrontal cortex of peer-reared females.

Conclusions

These findings suggest that exposure to an adverse early-life environment during infancy is associated with long-term alterations in the serotonin system and support previous studies suggesting that reduced 5-HT_1AR density during development might be a factor increasing vulnerability to stress-related neuropsychiatric disorders. Furthermore, alterations in the serotonin system seemed to be gender- and region-specific, providing a biological basis for the higher prevalence of affective disorders in women.

Key Words: Development, early-life stress, nonhuman primate, PET, serotonin_1A receptor