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. 2025 Jun 24;15(1):213.
doi: 10.1038/s41398-025-03434-z.

Not just old wine in new bottles: Polygenic liability for ADHD is associated with electrophysiological affective-motivational processing beyond anxiety, depression, and ODD

Kristóf Ágrez #  1 , Zsombor Visky #  2 , György Hámori  1   3 , Mária Takács  1   3 , Attila J Pulay  4 , János M Réthelyi  1   4 , Nóra Bunford  5   6
Affiliations

Not just old wine in new bottles: Polygenic liability for ADHD is associated with electrophysiological affective-motivational processing beyond anxiety, depression, and ODD

Kristóf Ágrez et al. Transl Psychiatry. .

Abstract

In attention-deficit/hyperactivity disorder (ADHD), emotional features account for heterogeneity and exacerbate severity of behavioral and functional impairments, beyond cognitive and comorbidity features. Yet, debate remains about the extent to which, in ADHD, such emotional features are a "core feature", i.e. whether ADHD should be conceptualized as encompassing difficulties with regulating not only activity, attention, and impulses but also processing and regulating emotions. We aimed to address this issue by examining the extent to which in adolescents, ADHD polygenic scores (PGSs) are associated with electrophysiological indices of affective-motivational processing, measured during a monetary punishment/reward feedback paradigm. ADHD PGSs were negatively associated, in n = 166 adolescents (Mage = 15.76 years, SD = 1.07; 42.77% girls), with amplitude values of an occipitoparietal event-related potential (i.e. late positive potential) and were positively associated, in n = 84 adolescents (Mage = 15.76 years, SD = 1.05; 41.67% girls), with fronto-centro-parietal alpha event-related desynchronization. Across analyses, covariates were anxiety, depression, and ADHD with comorbid disruptive behavior disorder PGSs; ADHD, internalizing, and oppositional defiant disorder severity; childhood maltreatment; current ADHD medication; and baseline values of the outcome. Findings were replicated in sensitivity analyses with blocks of conceptually related covariates entered separately. In adolescents, electrophysiological indices of affective-motivational processing are associated principally with genetic liability for ADHD but not comorbidity genetic liability or comorbidity manifest symptoms.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethical standards: The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. Dedication: This work is dedicated to the memory of the late William Pelham Jr. As a doctoral student, in 2010, NB presented her ideas on emotion dysregulation and ADHD to Dr. Pelham, who challenged them, asking whether emotion dysregulation in ADHD was “nothing but old wine in new bottles.” His questioning became a catalyst, inspiring NB’s program of research—culminating in this manuscript—designed to establish a different perspective.

Figures

Fig. 1
Fig. 1. LPP to win and loss.
A Baseline scalp distributions depicting activation to win (LPP to win) and lose (LPP to lose) in the 1600-2200 ms time window, with electrodes selected for scoring the LPP (CP1, Cpz, Cp2, P1, Pz, P2, and Poz) in red. B Baseline ERP grand average waveforms of the win (blue) and lose (red) condition cues. ERPs were scored in the 1600-2200 ms time window indicated by grey shading. (C) Follow-up scalp distributions depicting activation to win (LPP to win) and lose (LPP to lose) in the 1600-2200 ms time window, with electrodes selected for scoring the LPP (CP1, Cpz, Cp2, P1, Pz, P2, and Poz) in red. (D) Follow-up ERP grand average waveforms of the win (blue) and lose (red) condition cues. ERPs were scored in the 1600-2200 ms time window indicated by grey shading.
Fig. 2
Fig. 2. Event-related spectral perturbation of fronto-centro-parietal EEG power.
Figure depicts event-related desynchronization of fronto-centro-parietal EEG power in the 1000-3000 ms post-feedback time window (scored at F1, Fz, F2, FC1, Fz, FC2, C1, Cz, C2, CP1, CPz, CP2, P1, Pz, P2, and POz), with the average of alpha calculated in the 5-14 Hz frequency range, in the 1600-2200 ms time window) for adolescents at A baseline and B 18-month follow-up.
Fig. 3
Fig. 3. In adolescents, ADHD PGSs are associated with electrophysiological affective-motivational processing.
A ADHD PGSs are associated, prospectively, with LPP to win. B ADHD PGSs are associated, prospectively, with fronto-centro-parietal alpha ERD. Note. Residualized LPP scores are created by regressing all covariates (current ADHD, internalizing, and ODD severity, current ADHD pharmacotherapy, childhood maltreatment, anxiety PGSs, depression PGSs, ADHD with comorbid DBD PGSs, as well as the first four genetic principal components and baseline LPP to win values) onto follow-up LPP to win values. Residualized ERD scores are created by regressing all covariates (current ADHD, internalizing, and ODD severity, current ADHD pharmacotherapy, childhood maltreatment, anxiety PGSs, depression PGSs, ADHD with comorbid DBD PGSs, as well as the first four genetic principal components and baseline alpha ERD values) onto follow-up ERD values. Data points are weighted using the analysis weights obtained from the robust regression model presented in the text.
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