If the distinction of primary and secondary anxiety disorder carries with it little significance other than to screen out obvious cases of anxiety disorder that will remit spontaneously after relatively brief periods of abstinence, how can we understand the etiology and pathogenesis of comorbid anxiety and substance use disorders? Whereas a limited number of familial and genetic studies suggest that anxiety disorders and depression share a common genetic loading (), no evidence supports a common genetic loading between anxiety disorders and substance use disorders. An anxiety disorder might unmask the vulnerability to develop a substance use disorder, or contribute to the progression and severity of that disorder, or alter the response to treatment, and vice versa. However, these possibilities have not been examined systematically. How substance use unmasks anxiety disorder may be specific for different anxiety disorders. Kendler et al. () studied a population of female twins and showed that phobic disorders differed in how much of the concordance between twins was explained by common and specific genetic and environmental factors. Exposure to substances, therefore, could have differential effects on the emergence of specific anxiety disorders. Recent studies by Breslau et al. () attempted to identify the precursors and sequelae of traumatic events and posttraumatic stress disorder for men and women. Breslau et al. () found that in women, posttraumatic stress disorder predisposed to the development of an alcohol use disorder; however, even when more circumscribed analytical designs were used, it was difficult to determine whether the posttraumatic stress disorder caused the alcohol use disorder or whether the traumatic event exposed underlying vulnerabilities. To complicate matters, socioeconomic factors, ethnicity, and the predisposition to neuroticism appear to influence the likelihood of exposure to traumatic events (1995).
Cravings to abuse substances followed by substance use often have been compared to obsessive-compulsive behavior. In the Epidemiological Catchment Area study, obsessive-compulsive disorder () was more prevalent in alcoholic patients than in the general community at a level intermediate between phobic disorders and panic (), and disorders theorized to be part of an obsessive-compulsive disorder spectrum, such as pathological gambling, also have been linked to increased levels of substance use disorder (1997). London et al. () proposed that persons who abuse substances and individuals with obsessive-compulsive disorder may be unable to terminate inappropriate responses even when they know better. Based on the finding that obsessive-compulsive disorder is associated with an abnormality of orbitofrontal cortex function, Grant et al. () hypothesized that persons who abuse substances may share a similar abnormality. It is also possible that persons who abuse substances and who have comorbid obsessive-compulsive disorder or obsessive-compulsive disorder spectrum disorders represent a subgroup who may respond preferentially to agents used to treat obsessive-compulsive disorder in the same way that persons who abuse substances with attention-deficit/hyperactivity disorder may respond preferentially to psychostimulants.
Neurobiological studies of addiction and of anxiety disorders support the plausibility that each type of disorder could either cause the other or expose a vulnerability to the other. The sensitization of the amygdala through substance use may predispose to panic or elements of posttraumatic stress disorder. Neural adaptation to substance exposure could restrict normal cognitive processes, resulting in more severe substance problems, pathological memory in posttraumatic states, and a restricted cognitive focus in generalized anxiety or phobias. The pro- or asocial effects of addictive substances could influence the avoidant features of anxiety disorders. Conversely, it is plausible that anxiety disorders sensitize the brain to the reinforcing effects of psychoactive substances or lower an individual’s resistance to use these substances.