Original Article

Neuropsychopharmacology (2009) 34, 1936–1945; doi:10.1038/npp.2009.27; published online 4 March 2009

Risk Markers for Depression in Adolescents: Sleep and HPA Measures

Uma Rao1, Constance L Hammen2 and Russell E Poland3

  1. 1Department of Psychiatry, the University of Texas Southwestern Medical Center, Dallas, TX, USA
  2. 2Department of Psychology, the University of California, Los Angeles, CA, USA
  3. 3The Research and Education Institute for Texas Health Resources, Arlington, TX, USA

Correspondence: Dr U Rao, Department of Psychiatry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Mail Box 9101, Dallas, TX 75390-9101, USA. Tel: +214 648 5288; Fax: +214 648 5242; E-mail: uma.rao@utsouthwestern.edu

Received 4 October 2008; Revised 3 February 2009; Accepted 5 February 2009; Published online 4 March 2009.



Previous work has demonstrated reliable electroencephalographic (EEG) sleep and hypothalamic-pituitary-adrenal (HPA) changes associated with adult major depressive disorder. These changes might be evident before clinical manifestation of the illness in at-risk persons. The aim of the study was to identify depression-related EEG sleep and HPA changes in healthy adolescents at high risk for depression, and to examine the relationship between EEG sleep (or HPA) changes and the onset of depression. Forty-eight adolescent volunteers with no personal history of a psychiatric illness, including depression, but who were at high risk for developing depression by virtue of parental depression (high-risk group), and 48 adolescent volunteers with no personal or family history of a psychiatric disorder (normal controls) were recruited. EEG sleep and HPA measures were collected on three consecutive evenings and nights at baseline. Clinical follow-up evaluations were conducted at regular intervals over a 5-year period. Compared with normal controls, adolescents at high risk for depression had shorter latency to rapid eye movement (REM) sleep, increased phasic REM sleep, more REM sleep and elevated nocturnal urinary-free cortisol (NUFC) excretion at baseline. Shorter REM latency, higher REM density and elevated NUFC (measured at baseline) were associated with the development of depression during follow-up. The findings that REM sleep abnormalities and elevated HPA activity occur before the onset of depression in at-risk adolescents suggest that these variables serve as vulnerability markers for the illness.


cortisol, depression, development, EEG sleep, pediatric, vulnerability



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