Alcoholics frequently experience episodes of intense depression and/or severe anxiety. Depressed or anxious alcohol-dependent people often believe that they drink to relieve symptoms of sadness or nervousness. However, research does not unanimously support the prior existence of severe depressive or anxiety disorders as a usual cause of alcoholism. A review of recent literature (from family studies, prospective investigations, and studies of children of alcoholics) on the complex interaction between alcohol dependence and independent anxiety/depressive disorders reveals that if an association between alcoholism and anxiety/depressive disorders does exist, it likely operates in a relatively small subgroup of alcoholics at the same time. Psychological symptoms may carry a worse prognosis for alcohol-related problems, and these symptoms must be addressed early in alcoholism treatment.

Attributes of alcohol sensitivity are present before alcohol use disorders (AUDs) develop, they predict those adverse alcohol outcomes, are familial in nature, and many are heritable. Whether measured by alcohol challenges or retrospective reports of numbers of drinks required for effects, alcohol sensitivity reflects multiple phenotypes, including low levels of alcohol response and alcohol-related stimulation. Identification of genes that contribute to alcohol sensitivity could help identify individuals carrying risks for AUDs through their alcohol responses for whom early intervention might mitigate their vulnerability. Such genes could also improve understanding of biological underpinnings of AUDs, which could lead to new treatment approaches. However, the existing literature points to a wide range of genetic mechanisms that might contribute to alcohol responses, and few such genetic findings have been widely replicated. This critical review describes the potential impact of the diverse methods used to study sensitivity on the diversity of genetic findings that have been reported, places the genetic variants mentioned in the literature into broader categories rather than isolated results, and offers suggestions regarding how to advance the field by interpreting findings in light of the methods used to select research subjects and to measure alcohol sensitivity. To date, the most promising results have been for GABA, glutamate, opioid, dopamine, serotonin, and cholinergic system genes. The more gene variants that can be identified as contributors to sensitivity the better future gene screening platforms or polygenic scores are likely to be.

Men with a family history of alcoholism appear to have a lower intensity reaction to alcohol's effects than those without this family history. This study investigated whether a lower reaction could encourage greater alcohol consumption among family history-positive (FHP) subjects, predisposing them to develop alcohol-related problems. A family history of alcoholism was associated with increased risk of alcohol dependence and abuse among study subjects. Likewise, over half of the FHP's whose reactions to alcohol were low had developed alcoholism at a 10-year followup.

This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as part of the National Institute of Mental Health and later as an independent institute of the National Institutes of Health, NIAAA today is the world's largest funding agency for alcohol research. In addition to its own intramural research program, NIAAA supports the entire spectrum of innovative basic, translational, and clinical research to advance the diagnosis, prevention, and treatment of alcohol use disorder and alcohol-related problems. To celebrate the anniversary, NIAAA hosted a 2-day symposium, "Alcohol Across the Lifespan: 50 Years of Evidence-Based Diagnosis, Prevention, and Treatment Research," devoted to key topics within the field of alcohol research. This article is based on Dr. Schuckit's presentation at the event. NIAAA Director George F. Koob, Ph.D., serves as editor of the Festschrift.