The Effects of Alcohol and Cannabis Use on the Cortical Thickness of Cognitive Control and Salience Brain Networks in Emerging Adulthood: A Co-twin Control Study

Background: Impairments in inhibitory control and its underlying brain networks (control/salience areas) are associated with substance misuse. Research often assumes a causal substance exposure effect on brain structure. This assumption remains largely untested, and other factors (e.g., familial risk) may confound exposure effects. We leveraged a genetically informative sample of twins aged 24 years and a quasi-experimental co-twin control design to separate alcohol or cannabis exposure effects during emerging adulthood from familial risk on control/salience network cortical thickness. Methods: In a population-based sample of 436 twins aged 24 years, dimensional measures of alcohol and cannabis use (e.g., frequency, density, quantity, intoxications) across emerging adulthood were assessed. Cortical thickness of control/salience network areas were assessed using magnetic resonance imaging and defined by a fine-grained cortical atlas. Results: Greater alcohol, but not cannabis, misuse was associated with reduced thickness of prefrontal (e.g., dorso/ventrolateral, right frontal operculum) and frontal medial cortices, as well as temporal lobe, intraparietal sulcus, insula, parietal operculum, precuneus, and parietal medial areas. Effects were predominately (pre)frontal and right lateralized. Co-twin control analyses suggested that the effects likely reflect both the familial predisposition to misuse alcohol and, specifically for lateral prefrontal, frontal/parietal medial, and right frontal operculum, an alcohol exposure effect. Conclusions: This study provides novel evidence that alcohol-related reductions in cortical thickness of control/salience brain networks likely represent the effects of alcohol exposure and premorbid characteristics of the genetic predisposition to misuse alcohol. The dual effects of these two alcohol-related causal influences have important and complementary implications regarding public health and prevention efforts to curb youth drinking.