Neural predictors of substance use disorders in Young adulthood

Abstract

Offspring from multiplex, alcohol-dependent families are at heightened risk for substance use disorders (SUDs) in adolescence and young adulthood. These high-risk offspring have also been shown to have atypical structure and function of brain regions implicated in emotion regulation, social cognition, and reward processing. This study assessed the relationship between amygdala and orbitofrontal cortex (OFC) volumes obtained in adolescence and SUD outcomes in young adulthood among high-risk offspring and low-risk controls. A total of 78 participants (40 high-risk; 38 low-risk) from a longitudinal family study, ages 8–19, underwent magnetic resonance imaging; volumes of the amygdala and OFC were obtained with manual tracing. SUD outcomes were assessed at approximately yearly intervals. Cox regression survival analyses were used to assess the effect of regional brain volumes on SUD outcomes. The ratio of OFC to amygdala volume significantly predicted SUD survival time across the sample; reduction in survival time was seen in those with smaller ratios for both high-risk and low-risk groups. Morphology of prefrontal relative to limbic regions in adolescence prospectively predicts age of onset for substance use disorders.

Morphometric Biomarkers of Adolescents With Familial Risk for Alcohol Use Disorder

“…Thus, although the limbic‐to‐PFC morphometric ratio might become a useful metric for predicting the onset of a substance use disorder within an older sample of adolescents, it is not appropriate for identifying exacerbated risk in a younger sample of adolescents. It is also important to note that limbic‐to‐PFC ratio differences might become pronounced in adolescents with a larger familial loading, as analyzed in prior work (see O'Brien and Hill, ). Thus, although adolescents in the current sample are at an exacerbated risk for developing addiction disorders, the limbic‐to‐PFC ratio differences might be present in even higher risk samples, results from greater familial predispositions with multiplex factors.…”

“…Given the mean participant age of 13.6 years in the current sample and the deliberate selection of substance‐naïve participants, FH− associated behavioral differences, such as more alcohol use, were not expected to emerge until a few years later (Kessler et al., ; O'Brien and Hill, ). Thus, the presence of cognitively and emotionally linked anatomical characteristics in the absence of direct behavioral differences might reveal early biomarkers of risk for AUD at an older age.…”

“…These analyses consisted of linear, quadratic, and cubic effects. Furthermore, in order to test for a volumetric developmental imbalance , ratios of limbic volumes (hippocampus and amygdala, separately) to the PFC volume were calculated for each hemisphere (O'Brien and Hill, ). These ratios were analyzed using the same models as described above.…”

Dimensions of Craving Interact with COMT Genotype to Predict Relapse in Individuals with Alcohol Use Disorder Six Months after Treatment

“…Genetics may be relevant in understanding individual differences in the experience of craving [ 32 ]. AUD demonstrates high heritability rates [ 33 , 34 ] and neural structural and functional differences exist between high-risk individuals with a family history of alcohol misuse and those that do not [ 35 , 36 , 37 ]. This suggests that genetics and associated neurotransmitter function may play an important role in risk for the development and maintenance of AUD.…”

Familial Risk for Alcohol Dependence and Brain Morphology: The Role of Cortical Thickness Across the Lifespan

“…These observations suggest that the morphological differences observed may antedate the development of AUD and reflect an underlying genetic susceptibility. Recently, it has been shown that morphological variation between high and low‐risk offspring with and without family histories of alcohol dependence may be associated with later development of substance use disorders (O'Brien and Hill, ).…”