Marilyn Cyr

Reduced Inferior and Orbital Frontal Thickness in Adolescent Bulimia Nervosa Persists Over Two-Year Follow-Up

OBJECTIVE Cross-sectional data suggest functional and anatomical disturbances in inferior and orbital frontal regions in bulimia nervosa (BN). Using longitudinal data, we investigated whether reduced cortical thickness (CT) in these regions arises early and persists over adolescence in BN, independent of symptom remission, and whether CT reductions are markers of BN symptoms. METHOD A total of 33 adolescent females with BN symptoms (BN or other specified feeding or eating disorder) and 28 healthy adolescents participated in this study. Anatomical magnetic resonance imaging and clinical data were acquired at 3 time points within 2-year intervals over adolescence, with 31% average attrition between assessments. Using a region-of-interest approach, we assessed group differences in CT at baseline and over time, and tested whether between- and within-subject variations in CT were associated with the frequency of BN symptoms. RESULTS Reduced CT in the right inferior frontal gyrus persisted over adolescence in BN compared to healthy adolescents, even in those who achieved full or partial remission. Within the BN group, between-subject variations in CT in the inferior and orbital frontal regions were inversely associated with specific BN symptoms, suggesting, on average over time, greater CT reductions in individuals with more frequent BN symptoms. CONCLUSION Reduced CT in inferior frontal regions may contribute to illness persistence into adulthood. Reductions in the thickness of the inferior and orbital frontal regions may be markers of specific BN symptoms. Because our sample size precluded correcting for multiple comparisons, these findings should be replicated in a larger sample. Future study of functional changes in associated fronto-striatal circuits could identify potential circuit-based intervention targets.

A longitudinal functional magnetic resonance imaging study of task control circuits and bulimic symptoms over adolescence

BACKGROUND Previous cross-sectional findings from adolescents and adults with Bulimia Nervosa (BN) suggest disturbances in fronto-striatal and cingulo-opercular task control circuits that support self-regulatory processes, including the resolution of cognitive conflict. Herein, we used longitudinal data to examine the developmental trajectories of such disturbances and how the functioning of these circuits relates to changes in BN symptoms over adolescence. METHODS Thirty-two adolescent females with BN symptoms and 28 healthy control (HC) adolescents participated in the study. Functional magnetic resonance images (fMRI) during performance of a Simon task were acquired at three time points within 2-year intervals over adolescence. From the initial sample, 70% and 30% of the participants completed the second and third time points, respectively. Participants who completed all study time points did not differ from those lost to attrition on baseline demographic characteristics or any outcome measures. Using a region-of-interest approach, growth curve models tested group differences in the trajectory of conflict-related activation in task control circuits over time. Cross-lagged panel models examined transactional relationships between conflict-related activation in the same regions and BN symptoms over time. RESULTS Growth curve models revealed different trajectories of conflict-related activation in right task control regions across BN and HC adolescents, such that HC but not BN adolescents showed activation decreases over time. These group differences were greatest when including only the BN adolescents whose symptoms remitted over time. Cross-lagged panel models revealed that less frequent bulimic episodes at first follow-up predicted later increases in conflict-related activation in bilateral task control regions. CONCLUSIONS These longitudinal findings suggest overengagement of task control circuits in BN adolescents, especially those most resilient to persistent illness. Such overengagement may compensate for regulatory disturbances, allowing them to regulate eating behaviors over development. Thus, task control circuits may constitute targets for early interventions that enhance self-regulatory control.

Abnormal fronto-striatal activation as a marker of threshold and subthreshold Bulimia Nervosa

This study aimed to determine whether functional disturbances in fronto‐striatal control circuits characterize adolescents with Bulimia Nervosa (BN) spectrum eating disorders regardless of clinical severity. FMRI was used to assess conflict‐related brain activations during performance of a Simon task in two samples of adolescents with BN symptoms compared with healthy adolescents. The BN samples differed in the severity of their clinical presentation, illness duration and age. Multi‐voxel pattern analyses (MVPAs) based on machine learning were used to determine whether patterns of fronto‐striatal activation characterized adolescents with BN spectrum disorders regardless of clinical severity, and whether accurate classification of less symptomatic adolescents (subthreshold BN; SBN) could be achieved based on patterns of activation in adolescents who met DSM5 criteria for BN. MVPA classification analyses revealed that both BN and SBN adolescents could be accurately discriminated from healthy adolescents based on fronto‐striatal activation. Notably, the patterns detected in more severely ill BN compared with healthy adolescents accurately discriminated less symptomatic SBN from healthy adolescents. Deficient activation of fronto‐striatal circuits can characterize BN early in its course, when clinical presentations are less severe, perhaps pointing to circuit‐based disturbances as useful biomarker or risk factor for the disorder, and a tool for understanding its developmental trajectory, as well as the development of early interventions.