Brainmarker-I differentially predicts remission to various attention- deficit/hyperactivity disorder treatments: a blinded discovery, transfer and validation study

BACKGROUND: Attention-deficit/hyperactivity disorder is characterized by neurobiological heterogeneity, possibly explaining why not all patients benefit from a given treatment. As a means to select the right treatment (stratification), biomarkers may aid in personalizing treatment prescription, thereby increasing remission rates.

METHODS: The biomarker in this study was developed in a heterogeneous clinical sample (N=4249), and first applied to two large transfer datasets, a priori stratifying young males (<18 years) with a higher individual alpha peak frequency (iAPF) to methylphenidate (N=336) and those with a lower iAPF to multimodal Neurofeedback, complemented with sleep coaching (N=136). Blinded, out-of-sample validations were conducted in two independent samples. In addition, the association between iAPF and response to Guanfacine and Atomoxetine was explored.

RESULTS: Retrospective stratification in the transfer datasets resulted in a predicted gain in normalized remission of 17-30%. Blinded out-of-sample validations for methylphenidate (N=41) and multimodal Neurofeedback (N=71) corroborated these findings, yielding a predicted gain in stratified normalized remission of 36% and 29%, respectively.

CONCLUSION: The present study introduces a clinically interpretable and actionable biomarker based on the iAPF assessed during resting-state electroencephalography. Our findings suggest that acknowledging neurobiological heterogeneity can inform stratification of patients to their individual best treatment and enhance remission rates.