We have continued to analyze this rich data set at the NIMH where we have also made substantial progress in defining the factors involved in the transmission of these conditions in families, particularly the family studies of Puerto Ricans and African American families. This study examined the familial transmission of anxiety disorders and substance abuse using a combination of the family study/longitudinal high risk paradigms. This study also investigated comorbidity between physical disorders and mood and anxiety disorders. These data have provided a valuable resource for trainees in our laboratory who have learned to analyze data on familial aggregation as we await the results of the ongoing studies in our research group. The results of the recent analyses have been used to refine the research questions and methods of the ongoing NIMH family study. The chief findings reveal specificity of familial aggregation of anxiety disorders in general and the panic and social phobia subtypes in particular. Likewise, there was familial aggregation of substance abuse, with some suggestion of specificity of specific drugs. In contrast, although there was no evidence for vertical transmission of nicotine dependence, there was an increased risk of nicotine dependence among siblings. With respect to physical disorders, it was found that anxiety disorders were most strongly associated with physical disorders in general, and that there was evidence for co-transmission of migraine with anxiety and mood disorders in families. During the past year, we have published two papers on comorbidity of mood and anxiety disorders with substance use disorders. The first paper showed that there was an elevated risk of life-time history of cannabis use disorders among siblings, adult offspring, and spouses of probands with cannabis use disorders. There is a latent familial factor underlying cannabis use disorders that was shared partially with alcohol abuse/dependence. Comorbid mood and anxiety disorders aggregated independently from cannabis use disorders in families. Equal elevation in the magnitude of the association among the first-degree adult relatives and spouses of probands with a cannabis use disorder suggests the probable contribution of both environmental and genetic factors. Our findings suggest that cannabis dependence is both a cause and consequence of anxiety and mood disorders, thereby highlighting the importance of integrating treatment and intervention in the mental health and substance treatment sectors. The second project that examines the familial and societal correlates substance use disorders, with mood and anxiety disorders by comparing Puerto Rican families residing in the mainland USA and Puerto Rico. We found that the rates for alcohol use were greater among San Juan youth than their migrant counterparts. By contrast, US migrant adolescents were more likely to use cannabis. A strong association was observed between parental and child substance use at both sites, particularly for boys, and offspring of probands with drug use disorders were at greatest risk for substance use and related disorders. Familial aggregation patterns did not vary substantially by site. Despite societal influences on the magnitude and patterns of substance use in migrant youth, the consistent influence of parental disorders across sites reveals that the cross-generational transmission of substance use disorders in prior studies extends to Hispanic families and is an important factor to consider in the development of prevention strategies. Public Health Impact: Future research of migrant samples may benefit from integrating family history in understanding the risk and protective factors for the development of substance use disorders. In this regard, the promotion of treatment and prevention programs targeting vulnerable Hispanic populations has been slow. A clear need exists for the expansion of intervention and prevention programs for high-risk Hispanic youth, and in particular prior to the onset of behavioral and substance-related problems.