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Neurobehavioural analysis of reinforcement and its relevance for substance abuse: results from the IMAGEN study.

Gunter Schumann, MRC-SGDP Centre, Institute of Psychiatry, King’s College, London

Adolescent behaviour has been associated with substance abuse and dependence later in life. Individual variability in reinforcement processes (i.e., (impulsivity, novelty seeking, reward dependence) predict risk for addictions and describe motivations for drug use. Investigating how motivational and emotional cues affect individual variability in reinforcement behaviour at the genetic, neurobiological and cognitive levels might inform us about neurobehavioural mechanisms conferring risk for addictions, thus potentially maximizing the efficacy and efficiency of early interventions.

In the EC-FP6 Integrated Project IMAGEN, a European multicentric longitudinal gene x neuroimaging study, we aim to identify the genetic and neurobiological basis of individual variability in reinforcement behaviour and determine their predictive value for the development of addictions and other psychiatric disorders. Comprehensive behavioural and neuropsychological characterization, functional and structural neuroimaging and genome-wide association analyses of 2000 14-year-old adolescents at baseline are coupled with ongoing longitudinal follow-up at 16 and 19 years, and combined with functional genetics in animal and human models.

This lecture will focus on our recent investigations in 14 year-old adolescents of reinforcement mechanisms known to confer later risk for addictions. I will present structural and functional brain correlates of impulsivity (Schilling et al., Mol Psychiatry, in press) and describe how they relate to reward anticipation (Peters et al. Am J Psychiatry 2011) and risk taking (Schneider et al. Am J Psychiatry 2012) in substance abusing adolescents. I will discuss how gender and genetic factors influence neural mechanisms underlying novelty seeking and impulsivity (Nymberg et al., in review, in preparation), and how ADHD symptoms and early substance abuse are associated with distinct brain activity networks (Whelan et al., Nature Neuroscience, 2012; Jia et al, in preparation). Finally, I will discuss a novel mechanism underlying alcohol drinking behaviour, which has been discovered through translational research integrating animal, molecular and human gene x neuroimaging studies (Stacey et al. in preparation).

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