Although there is growing evidence for continuities in adolescent and adult depression, with similarities in clinical presentation and natural history, maturational differences also have been highlighted. Specifically, several studies reported greater variations in electroencephalographic (EEG) sleep changes, hypothalamic- pituitary-adrenal (HPA) activity and antidepressant (AD) response in depressed adolescents compared with the findings in adults. This proposal aims to understand the mechanism(s) underlying these developmental differences and to develop a strategy for use in identifying those patients, both youngsters and adults, who might benefit from AD treatment in general, and from bupropion treatment in particular. Based on the results of preliminary studies conducted in our laboratory, this investigation proposes to predict AD response to sustained-release bupropion in depressed adolescents and adults by assessing rapid eye movement (REM) sleep and HPA activity responses to single-dose bupropion administration prior to initiating treatment. Following completion of the sleep and neuroendrocrine assessments, subjects will receive clinical treatment with sustained-release bupropion for 8 weeks. In addition to examining the strength of association between REM sleep (and HPA) response to the bupropion challenge and clinical response to the drug, psychosocial measures (specifically stressful life experiences and social support) will be obtained in order to assess their contribution to AD response, both singly and in combination with the neurobiological measures. Bupropion was selected specifcally because of its relatively subtle effects on REM sleep compared with the other AD compounds (tricyclic agents and selective serotonin reuptake inhibitors, in particular). The robust REM sleep suppression induced by the other AD compounds might mask inter-individual variability;inherent differences in sensitivity that relate to treatment response could be lost due to a """"""""ceiling effect"""""""". Adolescent depression is a major public health problem that not only relates to the younger population, but also for the long-term mental health and social functioning of adults. Because depression in youngsters is associated with serious morbidity and mortality, and since it marks the gateway into recurrent mood disorders in a large proportion of adults, the early identification and effective treatment of depression in youngsters is of utmost importance. Because the long-term effects of AD agents on the developing human brain are not known, and because initial treatment can influence subsequent treatment compliance and clinical course, the identification of depressed youth who would (or would not) benefit from treatment with AD drugs is crucial. Results of the proposed study should not only be helpful in developing novel and more effective AD drugs and treatment strategies for youngsters, but also will enhance our understanding of the neurobiology of inadequate AD response in some adult patients with depression.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Avenevoli, Shelli A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Meharry Medical College
Schools of Medicine
United States
Zip Code
Clauss, Jacqueline Alexandra; Benningfield, Margaret M; Rao, Uma et al. (2016) Altered Prefrontal Cortex Function Marks Heightened Anxiety Risk in Children. J Am Acad Child Adolesc Psychiatry 55:809-16
Morris, Matthew C; Mielock, Alyssa S; Rao, Uma (2016) Salivary stress biomarkers of recent nicotine use and dependence. Am J Drug Alcohol Abuse 42:640-648
Adinoff, Bryon; Leonard, David; Price, Julianne et al. (2016) Adrenocortical sensitivity, moderated by ongoing stress, predicts drinking intensity in alcohol-dependent men. Psychoneuroendocrinology 76:67-76
Morris, Matthew C; Walker, Lynn S; Bruehl, Stephen et al. (2016) Impaired conditioned pain modulation in youth with functional abdominal pain. Pain 157:2375-81
Rao, Uma; Morris, Matthew C (2015) Cortisol Responses to Psychosocial Stress: The Role of Childhood Maltreatment and Depression. Int J Public Ment Health Neurosci 2:
Morris, Matthew C; Walker, Lynn; Bruehl, Stephen et al. (2015) Race Effects on Conditioned Pain Modulation in Youth. J Pain 16:873-80
Hellman, Natalie; Morris, Matthew C; Rao, Uma et al. (2015) Depression history as a moderator of relations between cortisol and shame responses to social-evaluative threat in young adults. Biol Psychol 109:159-65
Yang, Hongyu; Spence, Jeffrey S; Briggs, Richard W et al. (2015) Interaction between early life stress and alcohol dependence on neural stress reactivity. Addict Biol 20:523-33
Morris, Matthew C; Walker, Lynn; Bruehl, Stephen et al. (2015) Race effects on temporal summation to heat pain in youth. Pain 156:917-22
Morris, Matthew C; Evans, Lindsay D; Rao, Uma et al. (2015) Executive function moderates the relation between coping and depressive symptoms. Anxiety Stress Coping 28:31-49

Showing the most recent 10 out of 50 publications