The effects of alcohol and cannabis use on the cortical thickness of cognitive control and salience brain networks in emerging adulthood: a cotwin control study

Abstract 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 24-year-old twins and a quasi-experimental cotwin 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 24-year-old twins, 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 MRI 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. Cotwin control analyses suggested 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.