A pathway linking reward circuitry, impulsive sensation-seeking and risky decision-making in young adults: identifying neural markers for new interventions

Abstract

High trait impulsive sensation seeking (ISS) is common in 18–25-year olds, and is associated with risky decision-making and deleterious outcomes. We examined relationships among: activity in reward regions previously associated with ISS during an ISS-relevant context, uncertain reward expectancy (RE), using fMRI; ISS impulsivity and sensation-seeking subcomponents; and risky decision-making in 100, transdiagnostically recruited 18–25-year olds. ISS, anhedonia, anxiety, depression and mania were measured using self-report scales; clinician-administered scales also assessed the latter four. A post-scan risky decision-making task measured ‘risky' (possible win/loss/mixed/neutral) fMRI-task versus ‘sure thing' stimuli. ‘Bias' reflected risky over safe choices. Uncertain RE-related activity in left ventrolateral prefrontal cortex and bilateral ventral striatum was positively associated with an ISS composite score, comprising impulsivity and sensation-seeking–fun-seeking subcomponents (ISSc; P⩽0.001). Bias positively associated with sensation seeking–experience seeking (ES; P=0.003). This relationship was moderated by ISSc (P=0.009): it was evident only in high ISSc individuals. Whole-brain analyses showed a positive relationship between: uncertain RE-related left ventrolateral prefrontal cortical activity and ISSc; uncertain RE-related visual attention and motor preparation neural network activity and ES; and uncertain RE-related dorsal anterior cingulate cortical activity and bias, specifically in high ISSc participants (all ps<0.05, peak-level, family-wise error corrected). We identify an indirect pathway linking greater levels of uncertain RE-related activity in reward, visual attention and motor networks with greater risky decision-making, via positive relationships with impulsivity, fun seeking and ES. These objective neural markers of high ISS can guide new treatment developments for young adults with high levels of this debilitating personality trait.

Cluster analysis with MOODS‐SR illustrates a potential bipolar disorder risk phenotype in young adults with remitted major depressive disorder

“…Furthermore, any measurement that yields a single score for MDD likely misrepresents the heterogeneity of the disorder, and does not necessarily rule out bipolar spectrum symptoms. Furthermore, early in the course of the illness, a substantial minority of those presenting with MDD will later be diagnosed with BD …”

“…The VS regions, and these related constructs, are all potential sources of difference between MDD and BD. In particular, this region has shown differences in function and structure in those with BD and those at risk for the development of BD . A recent review has noted increased volume, decreased gray matter in those at risk, and increased activity at rest in the ventral striatum .…”

“…A recent review has noted increased volume, decreased gray matter in those at risk, and increased activity at rest in the ventral striatum . Disrupted connectivity between the VS and other regions of the brain may represent an early neural marker of BD . Abnormalities and disruptions to this region may correspond to the onset and risk for developing BD.…”

“…Furthermore, early in the course of the illness, a substantial minority of those presenting with MDD will later be diagnosed with BD. 6,7 It is well understood that BD is often missed in screening batteries for those presenting with mood spectrum pathology and initial evaluations for major depressive disorder. 8 For example, BD is often incorrectly diagnosed and not treated until 10-20 years after onset, usually about 14 years.…”

Neuroimaging tests for clinical psychiatry: Are we there yet?

“…Mary Phillips' research group reports that, in patients with bipolar depression, emotional dysregulation is associated with disturbed connectivity in the limbic circuitry implicated in negative mood states; 9 high sensation-seeking youth exhibit frontostriatal connectivity alterations across diagnoses. 33 Together, this rapidly accumulating body of work suggests that it is no longer incautious to propose that psychiatric biomarkers are within our reach, taking us closer to precision diagnoses, prognoses and treatment.…”