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Links Between Depression and Substance Abuse in Adolescents: Neurobiological Mechanisms

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Abstract

Adolescence is a high-risk period for development of both depressive and substance use disorders. These two disorders frequently co-occur in adolescents and are associated with significant morbidity and mortality. Given the added economic and psychosocial burden associated with the comorbid condition, identification of risk factors associated with their co-occurrence is of great public health importance. Research with adult animals and humans has indicated several common neurobiological systems that link depressive and addictive disorders. Given the ongoing maturation of these systems throughout adolescence and early adult life, it is not clear how these neurobiological processes influence development and progression of both disorders. A better understanding of the pathophysiological mechanisms leading to the onset and course of these disorders during adolescence will be helpful in developing more effective preventive and treatment strategies, and thereby allow these youth to reach their full potential as adults.

Introduction

The prevalence of depression in adolescents is on the rise, and depressive illness during this developmental period is associated with significant impairment in multiple social domains. Also, there is evidence that early depressive episodes persist into adult life along with ongoing psychosocial difficulties. Substance abuse often co-occurs with depression in adolescents, and their co-occurrence is associated with significant added psychosocial and economic burden. A better understanding of the pathophysiological mechanisms linking these two disorders is critical for developing more-effective treatment interventions for this disabling condition. However, most of the research on the neurobiology of depressive and addictive disorders is based on studies in adult animals and humans. Because many of these neurobiological systems continue to develop throughout adolescence, the immaturity of some of these systems might play a role in the progression of these disorders. For instance, evidence from animal studies indicates that adolescent substance use can induce stronger effects on the brain than in adults, consequently leading to more severe dependence-related behaviors and problems. Also, it is often difficult to determine whether the observed neurobiological alterations in adult populations preceded the manifested illness, and thereby serve as vulnerability markers, or whether they resulted from repeated drug use and/or multiple depressive episodes. Therefore, knowledge of developmental differences in neurobiological processes involved in comorbid depression and substance abuse will aid in developing more-specific interventions early and potentially prevent disease progression.

This paper summarizes research on the epidemiology, clinical course, and prognosis of co-occurring depressive and addictive disorders in adolescents. Based on data from adult animals and humans, common neurobiological processes that link these two disorders will be described. An argument will be made for studying developmental influences on these pathophysiological mechanisms as a basis for early treatment and prevention. A few caveats are warranted in interpreting adolescent data. First, the transition to adolescence involves chronological age as well as physical, biological, and social changes. In the pertinent clinical research reviewed here, youths aged 12 years and older, regardless of other changes, were considered as adolescents. Postnatal days 28 to 42 in rats and late-juvenile and sub-adult periods in nonhuman primates were considered to be the adolescent period. Second, there is an important distinction between experimental/infrequent and regular, problematic substance use. Although the mechanisms that drive progression from experimentation to abuse and dependence are not fully known, it is recognized that each stage might be preceded by unique conditions. Evidence suggests that experimentation with tobacco, alcohol, and other drugs is likely to result chiefly from social influences, whereas progression to dependence is more closely tied to internal processes, such as emotional and/or physiological characteristics. This review will focus on levels of substance use that would meet criteria for a diagnosis of abuse or dependence.

Section snippets

Links Between Depression and Addictive Disorders: Epidemiologic Perspective

Adolescence is a high-risk period for development of depressive and addictive disorders, with incident rates of each disorder estimated as high as 5% a year.1, 2, 3, 4, 5, 6, 7 In fact, information obtained from adult community samples indicated that the highest hazard rates for the onset of major depressive disorder as well as alcohol and drug dependence are between 15 and 19 years of age.8, 9 Several epidemiologic studies have shown that depressive illness and substance abuse frequently

Links Between Depression and Addictive Disorders: Clinical Perspective

From a clinical perspective, three lines of evidence support the hypothesis that depressive and addictive disorders are linked. Dysphoric or depressive mood is a common feature during withdrawal from several drugs of abuse, including alcohol, nicotine, opiates, and psychostimulants.29, 30 It is suggested that alterations in reward and motivational processes might play a central role in the manifestation of core symptoms of both disorders.31, 32, 33 For example, depressed mood and anhedonia, the

Neurobiological Correlates of Depression and Addictive Disorders

As stated previously, most of the information on the neurobiology of depression and addictive disorders comes from research in adult animals and humans. Even from these data, direct comparisons between the neurobiology of these disorders are difficult to make because the two fields of research have taken different approaches to investigating the neurobiological processes, and parallel studies of both disorders are very limited. Nevertheless, similar to information on overlapping clinical

Summary

In this review, common neurobiological processes that potentially mediate the links between depressive and addictive disorders were described. A review of neurobiological processes involved in these conditions must, by necessity, be selective in its approach and regretfully omit important advances in the field. In interpreting the data on the neurobiology of depressive and addictive disorders, it is important to note that the available information comes primarily from adult samples and research

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