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.
Impairments in inhibitory control and its underlying brain networks (controlsalience 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 controlsalience network cortical thickness. 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 controlsalience network areas were assessed using magnetic resonance imaging and defined by a fine-grained cortical atlas. Greater alcohol, but not cannabis, misuse was associated with reduced thickness of prefrontal (e.g., dorsoventrolateral, 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, frontalparietal medial, and right frontal operculum, an alcohol exposure effect. This study provides novel evidence that alcohol-related reductions in cortical thickness of controlsalience 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.