WHAT IS THE DIRECTIONALITY OF THE ONSET OF COMORBID SUBSTANCE USE AND OTHER PSYCHIATRIC DISORDERS?
Kevin P. Conway, Ph.D.
National Institute on Drug Abuse
Iván D. Montoya, M.D., M.P.H.
National Institute on Drug Abuse
Epidemiological and clinical studies routinely demonstrate extensive comorbidity between specific substance use and other psychiatric disorders. However, the directionality of their onset is not clear. Is it that substance use disorders trigger the onset of other psychiatric disorders? Or do individuals use drugs because of their mental disorder? Results from recent epidemiological, genetic and neurodevelopmental studies may be shedding light about the directionality of the onset of these disorders. Epidemiological studies are providing information about the age of onset and incidence of disorders. Genetic studies have shown common genetic predispositions to subsets of comorbid disorders and in some instances to specific combinations of comorbid conditions. Neurodevelopmental studies have shown the presence of abnormalities in neurobiological pathways that seem to antecede the development of comorbid conditions. Unfortunately, some of those studies still have methodological limitations including the reliability of data evaluating the onset and duration of the disorders, age of the subject, and period of time used to estimate disorder prevalence. Obtaining clear answers to the questions posed above is important in understanding the etiology of the disorders and planning treatment. Clinicians often try to identify the first condition to determine the most effective treatment approach. The purpose of this symposium is to discuss the directionality between substance use disorders and other psychiatric disorders, and their clinical implications.
Evidence of Directionality in Epidemiological Studies of Adults
Ronald Kessler, Ph.D.
The National Comorbidity Survey Follow-up (NCS-2) re-interviewed a probability sub-sample of respondents from the National Comorbidity Survey (NCS) a decade after the baseline NCS data collection. In order to study the extent to which temporally primary mental disorders predict the subsequent onset and progression of substance use disorders, the NCS-2 panel was used to study baseline (NCS) predictors of the first onset and progression of tobacco, alcohol, and illegal drug use, abuse, and dependence. A wide range of baseline (NCS) mental disorders significantly predicted increased risk of the subsequent (NCS-2) onset and persistence of nicotine use and dependence, while impulse-control disorders and, to a lesser extent, anxiety disorders predicted onset and progression of alcohol use disorders and illegal drug disorders. Further analysis is needed to study specification of these patterns as a function of multivariate profiles of mental disorders and age of onset of substance disorders.
Genetic Factors and the Directionality of Comorbid Disorders
Michael Vanyukov, Ph.D.
The directionality of relationships between substance use disorders (SUD) and comorbid conditions is often unclear. Arbitrariness and heterogeneity of diagnoses lead to changes in the definition and position of the diagnostic thresholds and in the relative timing of the landmarks of natural histories of the disorders. Genetic studies show that despite the diversity of addictive substances, genetic variation in the risks for disorders related to them is largely nonspecific and shared with other comorbid behavioral disorders. This suggests that mechanisms other than those involved in pharmacologic action may play a significant role. Attention is drawn to the psychological traits developmentally predating drug abuse, including liabilities to childhood behavioral disorders. Genetic overlap between some of these indicators of psychological regulation and liability to SUD points to common factors that are likely involved in neurotransmission, neuromaturation, and physiological maturation. Studies longitudinally tracking genetic relationships of behavioral development and providing information on their mediators at biochemical and physiological levels (including neuroimaging), combined with structured environmental data, may be able to disambiguate comorbidities and elucidate the individual trajectory to SUD.
Developmental Model to explain onset and directionality of comorbid disorders
Monique Ernst, Ph.D.
Directionality of onset of psychiatric disorders raises much interest because it can inform causality, and thus mechanisms underlying pathology. Here, a neurodevelopmental model of vulnerability to psychiatric disorders that are characterized by core deficits in reward systems is presented. We review findings from neuroimaging studies that address structural and functional patterns of neural circuitry engaged in reward-related processes, across both development and psychopathology. These findings concur to suggest that vulnerability to substance use and other psychiatric disorders could be conferred by the different timelines in maturation of neural circuits controlling behavior. Schematically, these circuits comprise the amygdala that promotes avoidance behavior, the ventral striatum that promotes approach behavior, and the medial prefrontal cortex that supervises these subcortical systems. Different maturational trajectories are proposed to result in states of imbalance relative to the normative adult coordination of motivated behavior. For example, risk taking behaviors peak in adolescence, and account for the sharp and paradoxical rise in morbidity and mortality during this period of life. The proposed model assumes a relative delay in maturation of the supervisory structures, in a context where the approach-related neural system is prominent relative to the avoidance behavior system. Although reductionistic, this model has the merit to be testable and to provide direction for the study of comorbid disorders.
At the conclusion of this presentation, the participant should be able to recognize the importance of the role of neurodevelopment in shaping deviant behavior as well as conferring risk for pathology emerging later in life. Designing environmental support that could help mitigate the consequences of a transient normative imbalance in the maturation of brain circuits that coordinate motivated behavior could be one way to avoid long-term health consequences. The participant should become sensitive to this issue that promotes the implementation of preventive measures early in life, particularly during adolescence.
Treatment Implications of Determining the Directionality of Comorbid Disorders
Edward V. Nunes, M.D.
Co-occurring psychiatric disorders are associated with poor treatment outcome in substance-dependent patients, suggesting the hypothesis that specific treatment of co-occurring disorders should improve substance use outcome. However, accurate diagnosis of co-occurring disorders (e.g., depression) has been a challenge, since substance abuse may induce psychiatric symptoms. We review naturalistic studies on the impact of comorbidity on treatment outcomes of substance use disorders, and placebo-controlled trials of antidepressant medications in depressed, substance-dependent patients. The findings suggest that a careful diagnosis that takes account of the order of onset and offset of depression in relation to substance use is important in identifying depressive syndromes that affect prognosis and response to treatment. This supports the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) definition of independent depression, as opposed to substance-induced depression, although more research is needed to directly test the treatment implications of these diagnostic categories. This presentation explains the problems inherent in diagnosing psychiatric disorders among substance dependent patients; the DSM-IV categories of primary (independent) and substance-induced depression;
and the data from clinical trials supporting the effectiveness of antidepressant treatment among depressed substance dependent patients, and the importance of diagnosis.