Comorbidity Between Depressive and Addictive Disorders in Adolescents— The Role of Stress and Limbic–Hypothalamic–Pituitary–Adrenal Activity

Uma Rao
US Psychiatry, 2010;3:39-43
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Abstract

Adolescents are at heightened risk for the development of both depressive and addictive disorders. These two disorders frequently co-occur in adolescents and are associated with significant morbidity and mortality. Given the substantial economic and psychosocial burden associated with the comorbid condition, the identification of causal mechanisms associated with their co-occurrence is of great public health importance. Evidence indicates that psychosocial stress contributes to the initiation and maintenance of both depressive and addictive disorders. Research suggests that the limbic–hypothalamic–pituitary–adrenal (LHPA) axis may be important in the development of depression as well as addictive disorders. Using a diathesis–stress model, this review will examine the interactions between stressful experiences and the LHPA axis in increasing the risk for depressive and addictive disorders in adolescents. Emerging evidence suggests that the high rates of comorbidity between these two disorders may be explained, in part, by high levels of stress and altered LHPA activity. Clinical implications of these associations will be discussed.

Acknowledgments: This work was supported, in part, by grants DA14037, DA15131, DA17804, DA17805, MH01419, MH62464, and MH68391 from the National Institutes of Health, and by the Sarah M and Charles E Seay Endowed Chair in Child Psychiatry at The University of Texas Southwestern Medical Center. The author would also like to express gratitude to Li-Ann Chen, MA, for technical support.
Keywords
Adolescence, addictive disorder, alcohol, cortisol, depression, drug addiction, limbic–hypothalamic–pituitary–adrenal (LHPA) axis, limbic system, neurobiology, stress, vulnerability
Disclosure The author has no conflicts of interest to declare.
Received: December 18, 2009 Accepted March 08, 2010
Correspondence: Uma Rao, MD, Department of Psychiatry, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9101. E: uma.rao@utsouthwestern.edu

Depression is a leading cause of morbidity and mortality in adolescents. Elevated risk for the disorder begins in the early teens and continues to rise in a linear fashion throughout adolescence, with lifetime rates estimated to range from 15 to 25% by late adolescence.1–3 Numerous studies have also documented that adolescent depressive episodes persist or recur into adult life along with ongoing psychosocial difficulties.4,5 These difficulties include, but are not limited to, disruption in interpersonal relationships, early pregnancy, low educational attainment, poor occupational functioning, and unemployment, as well as increased risk for suicidal behavior, resulting in a substantial socioeconomic burden.4,5

Substance abuse also typically emerges during adolescence,6,7 and early onset of substance abuse is associated with a stable and escalating course into adulthood.8–10 Depressive and addictive disorders frequently co-occur among adolescents and adults, and when they occur together, adaptive function is compromised further.7,11–13 The co-occurrence of substance use disorder (SUD) with depression in adolescents is associated with earlier onset and more severe substance-related problems, increased frequency of behavioral problems, more prolonged and recurrent depressive episodes, and more severe impairment in family, school, and legal domains. Youth with the comorbid disorder are also at higher risk for suicidal behavior than those without comorbidity.11,13,14 As a result, the comorbid illness is associated with increased utilization of health services and substantially higher treatment costs compared with those who have only depression or SUD.15 Given the economic and psychosocial burden associated with comorbid depressive and addictive disorders, understanding the underlying mechanisms associated with these comorbid conditions is of great public health importance.

Although significant advances have been made with regard to knowledge of the environmental and neurobiological factors involved in depression and substance-related disorders individually, especially in adults, the mechanisms underlying the comorbid illness are not well understood.13,16 It is likely that the high prevalence of these disorders occurring together reflects, in part, overlapping genetic, environmental, and neurobiological factors. It is also possible that there will be differences in neurobiology based on the temporal course of development of these two disorders, whether depression precedes substance abuse or the reverse.

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Comorbidity Between Depressive and Addictive Disorders in Adolescents— The Role of Stress and Limbic–Hypothalamic–Pituitary–Adrenal Activity

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