Functional Connectivity Mechanisms Underlying Symptom Reduction Following Lisdexamfetamine Treatment in Binge-Eating Disorder: A Clinical Trial.

Background: Speculation exists as to whether lisdexamfetamine dimesylate (LDX) acts on the functional connectivity (FC) of brain networks that modulate appetite, reward, or inhibitory control in binge-eating disorder (BED). Better insights into its action may help guide the development of more targeted therapeutics and identify who will benefit most from this medication. Here, we use a comprehensive data-driven approach to investigate the brain FC changes that underlie the therapeutic action of LDX in patients with BED. Methods: Forty-six participants with moderate to severe BED received LDX titrated to 50 or 70 mg for an 8-week period. Twenty age-matched healthy control participants were also recruited. Resting-state functional magnetic resonance imaging was used to probe changes in brain FC pre- and post treatment and correlated with change in clinical measures. Results: Ninety-seven percent of trial completers (n = 31) experienced remission or a reduction to mild BED during the 8-week LDX trial. Widespread neural FC changes occurred, with changes in default mode to limbic, executive control to subcortical, and default mode to executive control networks associated with improvements in clinical outcomes. These connections were not distinct from control participants at pretreatment but were different from control participants following LDX treatment. Pretreatment connectivity did not predict treatment response. Conclusions: FC between networks associated with self-referential processing, executive function, and reward seem to underlie the therapeutic effect of LDX in BED. This suggests that LDX activates change via multiple systems, with most changes in compensatory networks rather than in those characterizing the BED diagnosis.

Cognitive and Executive Contributions to Trail-Making Task Performance on Adolescents With and Without Attention Deficit Hyperactivity Disorder.

OBJECTIVE: The trail making task is used to assess executive functioning in ADHD youth, yet has only been validated in adult populations. We compare the relative contributions of various cognitive measures to performance on a trail making task analog, the Switching of Attention (SoA) task, in typically-developing and ADHD adolescents. METHOD: Participants were 160 adolescents with ADHD from the International Study to Predict Optimized Treatment-in ADHD, assessed at pretreatment baseline and 6-week medicated follow-up, and 160 matched typically-developing peers. Attention, processing speed, working memory, impulsivity, and motor speed were assessed using a cognitive battery. RESULTS: Processing speed and working memory significantly contributed to SoA performance in ADHD, regardless of medication status. While medicated, motor speed also underpinned the prediction of most task measures. For typically-developing adolescents, sustained attention and working memory contributed to SoA performance. CONCLUSION: Typically-developing, unmedicated and treated ADHD adolescents recruit different aspects of cognition during SoA completion.

Impulsivity and Its Relationship With Lisdexamfetamine Dimesylate Treatment in Binge Eating Disorder.

High trait impulsivity is thought to contribute to the sense of loss of control over eating and impulses to binge eat experienced by those with binge eating disorder (BED). Lisdexamfetamine dimesylate (LDX), a drug approved for treatment of moderate to severe BED, has been shown to decrease impulsive features of BED. However, the relationship between LDX-related reductions of binge eating (BE) episodes and impulsivity has not yet been explored. Forty-one adults aged 18-40years with moderate to severe BED completed questionnaires and tasks assessing impulsivity at baseline and after 8weeks of 50-70mg of LDX. Twenty age-matched healthy controls were also assessed at two timepoints for normative comparison. Data were analysed using linear mixed models. BED participants exhibited increased self-reported motor, non-planning, cognitive and food-related impulsivity relative to controls but no differences in objective task-based measures of impulsivity. Food-related and non-planning impulsivity was significantly reduced by LDX, but not to normative levels. Individuals with higher baseline levels of motor and non-planning impulsivity, and loss of control over eating scores experienced the greatest reduction in BE frequency after 8weeks of LDX. Further, there were significant associations between the degree to which subjective loss of control over eating, non-planning impulsivity and BE frequency reduced after 8weeks of LDX. These data suggest that specific subjective measures of impulsivity may be able to predict who will have the greatest benefit from LDX treatment and that reductions in BE frequency may be moderated by concurrent reductions in non-planning impulsivity.