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The potential for integrating comorbidity research with stress research Kushner et al. (2012b) used a latent variable modeling approach to show that it is the shared rather than unique variance among common internalizing disorders that relates to risk for alcohol dependence. Also, Kushner et al. (2011) and Kushner et al. (2012a) support the hypothesis that the same sensitivity to allostatic dysregulation in the brain��s stress and affect response systems (e.g., sympathoadrenal-medullary complex) could render individuals vulnerable to both the development of internalizing disorders and the development of dependence on multiple substances of abuse. Along these same lines, several recent articles selleck inhibitor find overlapping neurobiological structures and processes underlying a variety of psychiatric disturbances and substance dependence (McElligott et al., 2013; Moonat et al., 2013; Saal et al., 2003). In fact, an entire recent issue of the National Institute on Alcohol Abuse and Alcoholism��s journal Alcohol Research: Current Reviews (34[4], 2012) was devoted to the association of neurobiological stress systems to the use of alcohol and development of dependence. Integrating these emerging neurobiological approaches with the already well-developed epidemiological, genetic, and cognitive approaches and findings reviewed here could constitute a new era of comorbidity research with the potential to achieve the elusive goal of developing a general working model of comorbidity that is both intellectually satisfying and clinically productive. Concluding remarks As described by Thomas Kuhn (1962), science normally moves forward bepotastine slowly and steadily but is occasionally punctuated by rapid revolutionary changes in how problems are understood and studied. We have seen both aspects of science in the comorbidity research published over the past 75 years. The successes of the past 75 years generate much excitement and optimism to see what the future holds as we progress toward the journal��s 100th anniversary and beyond. Footnotes This work was supported by National Institute on find more Alcohol Abuse and Alcoholism Grant K02-AA0017886 (to Matt G. Kushner).""Modern pharmacotherapy for alcohol use disorders had its genesis in two seminal events: the repeal of National Prohibition in the United States in 1933 and the establishment of Alcoholics Anonymous (AA) in 1935. Although these events did not lead directly to the use of medications (and, in fact, AA has opposed the use of medications that can potentially cause dependence or that are intended to help heavy drinkers reduce, rather than stop, drinking), they contributed to the view that alcoholism is a treatable disease that may be amenable to pharmacotherapy (Levine, 1984). Prohibition��s advocates had argued that the elimination of alcoholic beverages would end alcoholism and all its associated evils.