The development of treatment biomarkers for psychiatric disorders has been challenging, particularly for heterogeneous neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD). Promising findings are also rarely translated into clinical practice, especially with regard to treatment decisions and development of novel treatments. Despite this slow progress, the available neuroimaging, electrophysiological (EEG) and genetic literature provides a solid foundation for biomarker discovery. This article gives an updated review of promising treatment biomarkers for ADHD which may enhance personalized medicine and novel treatment development. The available literature points to promising pre-treatment profiles predicting efficacy of various pharmacological and non-pharmacological treatments for ADHD. These candidate predictive biomarkers, particularly those based on low-cost and non-invasive EEG assessments, show promise for the future stratification of patients to specific treatments. Studies with repeated biomarker assessments further show that different treatments produce distinct changes in brain profiles, which track treatment-related clinical improvements. These candidate monitoring/response biomarkers may aid future monitoring of treatment effects and point to mechanistic targets for novel treatments, such as neurotherapies. Nevertheless, existing research does not support any immediate clinical applications of treatment biomarkers for ADHD. Key barriers are the paucity of replications and external validations, the use of small and homogeneous samples of predominantly White children, and practical limitations, including the cost and technical requirements of biomarker assessments and their unknown feasibility and acceptability for people with ADHD. We conclude with a discussion of future directions and methodological changes to promote clinical translation and enhance personalized treatment decisions for diverse groups of individuals with ADHD.

Background

Error processing and inhibitory control enable the adjustment of behaviors to meet task demands. Functional magnetic resonance imaging studies report brain activation abnormalities in patients with obsessive-compulsive disorder (OCD) during both processes. However, conclusions are limited by inconsistencies in the literature and small sample sizes. Therefore, the aim here was to perform a meta-analysis of the existing literature using unthresholded statistical maps from previous studies.

Methods

A voxelwise seed-based d mapping meta-analysis was performed using t-maps from studies comparing patients with OCD and healthy control subjects (HCs) during error processing and inhibitory control. For the error processing analysis, 239 patients with OCD (120 male; 79 medicated) and 229 HCs (129 male) were included, while the inhibitory control analysis included 245 patients with OCD (120 male; 91 medicated) and 239 HCs (135 male).

Results

Patients with OCD, relative to HCs, showed longer inhibitory control reaction time (standardized mean difference = 0.20, p = .03, 95% confidence interval = 0.016, 0.393) and more inhibitory control errors (standardized mean difference = 0.22, p = .02, 95% confidence interval = 0.039, 0.399). In the brain, patients showed hyperactivation in the bilateral dorsal anterior cingulate cortex, supplementary motor area, and pre-supplementary motor area as well as right anterior insula/frontal operculum and anterior lateral prefrontal cortex during error processing but showed hypoactivation during inhibitory control in the rostral and ventral anterior cingulate cortices and bilateral thalamus/caudate, as well as the right anterior insula/frontal operculum, supramarginal gyrus, and medial orbitofrontal cortex (all seed-based d mapping z value >2, p < .001).

Conclusions

A hyperactive error processing mechanism in conjunction with impairments in implementing inhibitory control may underlie deficits in stopping unwanted compulsive behaviors in the disorder.

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.