Development of alcohol use disorders: the role of clinical, psychological, environmental, genetic and neurobiological factors
04 / 2008 - unknown
This study examines determinants of the presence and course of alcohol use disorders (AUD) in a large high-risk cohort of patients with depressive and/or anxiety disorders. The following study objectives will be addressed:Objective 1: Prevalence, course and consequences of AUD 1a. What are the prevalence and 4-year course of AUD? 1b. What are AUD consequences on public health, i.e. mental and physical health, disability and health care utilization?1c. What are needs for care and experienced barriers to adequate care for AUD patients?Objective 2: Prediction of presence and course of AUD2a. Which psychological, environmental and clinical factors predict the prevalence and course of AUD?2b. Using a genome-wide approach, which genes are associated with vulnerability for AUD?2c. To what extent do important psychological, environmental, clinical and genetic factors interact in predicting presence and course of AUD?Objective 3: Neurophysiological mechanisms associated with (chronic) AUD3a. Is AUD associated with abnormal processing of emotional and motivational information, as shown by increased responsiveness to alcohol-related cues, and altered sensitivity to neutral emotional stimuli?3b. Is AUD associated with diminished cognitive control, as shown by behavioural inflexibility and deficient executive function?3c. Is chronic alcohol dependence, compared to non-chronic, characterized by a preponderance of deficient cognitive control and maladaptive habit formation, rather than reward seeking? Alcohol use disorders (AUD) are common and have an enormous public health impact. Although effective treatment strategies are available, the vast majority (>90%) of AUD patients do not receive appropriate treatment. Despite the enormous numbers of patients involved and the circumstance that simple and effective screening devices for AUD are available, tools to predict development and course of AUD among a high-risk population constitutes an important next step in efforts to address this important health problem. A specific high-risk group constitutes the population with depressive or anxiety disorders. As confirmed in other studies, our own preliminary data show for instance that the lifetime prevalence of alcohol dependence is seven times higher among patients with depressive or anxiety disorders than among healthy controls. Consequently, of all AUD patients, 60-70% also has a history of depressive or anxiety disorders. Being able to reliably predict which patients are at high risk to develop AUD would allow earlier intervention in those in need, while preventing unnecessary efforts to reach and treat those with a benign prognosis. Several factors have been hypothesized to contribute to AUD, including environmental, clinical, genetic and neurophysiological factors. However, these factors have never been examined comprehensively within one study and in a longitudinal perspective. Consequently, the relative importance of these factors as well as their potential interacting effects, are largely unknown. The present study provides a unique and cost-effective opportunity to examine the pathway to and course of AUD in a large high-risk cohort of 2981 persons with depressive and/or anxiety disorders as part of the Netherlands Study of Depression and Anxiety (NESDA). In this study, we will examine the concerted effects of clinical, psychological, environmental, genetic and neurophysiological pathways responsible for the presence and course of AUD.The primary objectives of the current proposal are the following: (i) to study the presence and course of AUD and its consequences in patients with depressive or anxiety disorders; (ii) to study the barriers to effective care for patients in different stages of development and severity of AUD (iii) to study the clinical, psychological, environmental and genetic predictors of (the course of) AUD; and (iv) to explore the neurophysiological basis for (chronic) AUD. NESDA is an ongoing longitudinal study in which 2981 persons have been recruited and will be re-assessed 1, 2, 4 and 8 years after baseline. The NESDA baseline assessment lasted on average four hours and included amongst others (psychiatric) interviewing, self-report questionnaires, medical examination and blood and DNA sampling. This has resulted in a rich data base with detailed information on clinical mental and somatic health indicators as well as on psychological, environmental and genetic factors. At study baseline, 812 persons have been identified with a diagnosis of AUD through psychiatric interviewing using the CIDI according to DSM-IV criteria (consisting of 459 alcohol dependence disorders and 353 alcohol abuse disorders). In order to address its objectives, this proposed study will extend NESDA with (i) additional follow-up assessments of AUD diagnoses and relevant characteristics (e.g. impulsive behavior, antisocial personality and ADHD symptoms); (ii) additional genotyping; (iii) additional fMRI assessments in subgroups of healthy controls, non-chronic and chronic AUD patients; and (iv) funding the junior investigators to address the key objectives. The results will provide unique, comprehensive data of the interplay between key factors and mechanisms involved in presence and chronicity of AUD, which may be targeted in the prevention and treatment of AUD as well as in the organization of services.