Different Changes in Brain Functional Networks Following 12-Week Psychostimulant Treatment in Attention-Deficit/Hyperactivity Disorder Youth With and Without Familial Risk for Bipolar I Disorder - 09/09/25
, Ziyu Zhu, PhD b, c : Candidate, Maxwell J. Tallman, MPH b, L. Rodrigo Patino, MD b, Qiyong Gong, MD, PhD c, f, ∗ , John A. Sweeney, PhD b, c, Melissa P. DelBello, MD b, Robert K. McNamara, PhD bAbstract |
Objective |
Although psychostimulants are the first-line treatment for attention-deficit/hyperactivity disorder (ADHD) and can normalize associated brain network abnormalities, their neural effects in ADHD youth with a family history of bipolar I disorder (BD) have not yet been systematically investigated.
Method |
This study investigated the effects of 12-week mixed amphetamine salts—extended release (MAS-XR) treatment on brain functional networks and symptom changes in ADHD youth with (“high-risk” [HR]) and without (“low-risk” [LR]) a first-degree relative with BD. LR received 12-week open-label MAS-XR and HR were randomized to MAS-XR or placebo (PLA). Healthy controls (HC) were included for comparative purposes. Resting-state functional magnetic resonance imaging scans were acquired at baseline and week 12. Global and nodal network topological metrics were evaluated based on functional connectivity matrices using graph theoretical analysis.
Results |
A total of 135 youth were included (HC, n = 45; LR-MAS, n = 46; HR-MAS, n = 28; HR-PLA, n = 16). For comparisons between HR-MAS and LR-MAS groups, significant group-by-time interactions were identified in global efficiency, characteristic path length, left superior parietal gyrus degree, and right amygdala efficiency. Relative to the HC group, all baseline abnormalities were normalized at week-12 in the LR-MAS group, whereas a decrease in right amygdala efficiency uniquely emerged in the HR-MAS group. Significant correlations were identified between changes in network topology and ADHD symptoms. Connectome-based predictive modeling analysis revealed that baseline network dysconnectivity predicted ADHD treatment outcomes in the HR-MAS group only.
Conclusion |
These findings provide novel evidence that ADHD youth with and without BD familial risk exhibit different changes in brain network topology and associated symptoms following 12 weeks of psychostimulant treatment.
Clinical trial registration information |
Neuroimaging Study of Risk Factors for Adolescent Bipolar Disorder (NERF); NCT02478788
Le texte complet de cet article est disponible en PDF.Key words : attention-deficit/hyperactivity disorder, connectome, magnetic resonance imaging, graph theory, stimulants
Plan
| This article was reviewed under and accepted by Paul E Croarkin, DO, MSCS. |
|
| This study was supported in part by R01 NIMH grant 097818 to R.K.M and M.P.D (Co-PIs); NIH had no further role in study design, in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. |
|
| Consent has been provided for descriptions of specific patient information. |
|
| Data Sharing: Researchers interested in accessing the data may contact the corresponding author to explore the possibility of sharing data under appropriate agreements that ensure compliance with ethical and legal guidelines. |
|
| Thomas Blom, MS, served as the statistical expert for this research. |
|
| Dr. John Sweeney passed away in 2023, prior to the final version of the manuscript being accepted. The authors are grateful for his contributions to the conceptualization and critical revision of the work |
|
| The authors thank Thomas Blom, MS, of the University of Cincinnati for assistance with the statistical analyses. |
|
| Disclosure: Kun Qin has received research funding from Hubei Provincial Natural Science Foundation of China (grant No. 2024AFB366). Nanfang Pan has received research funding from Natural Science Foundation of China (grant No. 823B2041). Du Lei has received research funding from Chongqing Talents Exceptional Young Talents Project (grant No. cstc2024ycjh-bgzxm0220) and Natural Science Foundation of Chongqing (grant No. CSTB2024NSCQ-MSX0377). L. Rodrigo Patino has received research funding from NIH, PCORI, Abbvie, Allergan, Janssen, Johnson and Johnson, Lundbeck, Lilly, Otsuka, Pfizer, and Sunovion. Qiyong Gong has received research funding from Natural Science Foundation of China. Melissa P. DelBello has received research support from NIH, PCORI, Acadia, Alkermes, Janssen, Johnson and Johnson, Lundbeck, Otsuka, Pfizer, Sage, Sunovion, and Vanda. She is also a consultant or on the advisory board for Alkermes, Allergan, Janssen, Johnson and Johnson, Lundbeck, Merck, Myriad, and Sage. Robert K. McNamara has received research support from Martek Biosciences Inc, Royal DSM Nutritional Products, LLC, Inflammation Research Foundation, Ortho-McNeil Janssen, AstraZeneca, Eli Lilly, NARSAD, and NIH, and previously served on the scientific advisory board of the Inflammation Research Foundation. Ziyu Zhu and John A. Sweeney have reported no biomedical financial interests or potential conflicts of interest. |
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?