ADHD Symptom Trajectories: Cortical Thinning and Hippocampal Expansion as Neural Signatures
Presented During:
Thursday, June 26, 2025: 11:30 AM - 12:45 PM
Brisbane Convention & Exhibition Centre
Room:
M1 & M2 (Mezzanine Level)
Poster No:
256
Submission Type:
Abstract Submission
Authors:
Wenjie Hou1, Barbara Sahakian2, Samuele Cortese3, Gunter Schumann1,4, Li Yang5,6, Tobias Banaschewski7, Qiang Luo1,8
Institutions:
1Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China, 2Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom, 3School of Psychology, University of Southampton, Southampton, United Kingdom, 4Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany, 5National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, China, 6NHC Key Laboratory of Mental Health, Peking University, Beijing, China, 7Department of Child and Adolescent Psychiatry and Psychotherapy, Heidelberg University, Mannheim, Germany, 8State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China
First Author:
Wenjie Hou
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Shanghai, China
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Shanghai, China
Co-Author(s):
Gunter Schumann
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University|Department of Psychiatry and Psychotherapy, Technische Universität Dresden
Shanghai, China|Dresden, Germany
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University|Department of Psychiatry and Psychotherapy, Technische Universität Dresden
Shanghai, China|Dresden, Germany
Li Yang
National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital|NHC Key Laboratory of Mental Health, Peking University
Beijing, China|Beijing, China
National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital|NHC Key Laboratory of Mental Health, Peking University
Beijing, China|Beijing, China
Tobias Banaschewski
Department of Child and Adolescent Psychiatry and Psychotherapy, Heidelberg University
Mannheim, Germany
Department of Child and Adolescent Psychiatry and Psychotherapy, Heidelberg University
Mannheim, Germany
Qiang Luo
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University|State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University
Shanghai, China|Shanghai, China
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University|State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University
Shanghai, China|Shanghai, China
Introduction:
Attention-deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental condition affecting around 5% of children and adolescents world-wide. ADHD is characterized by its significant clinical heterogeneity, including different symptom courses, such as persistent, remitting, and emergent trajectories during adolescence and adulthood, which may be affected by pharmacological treatments. More importantly, the neurodevelopmental mechanisms underlying heterogeneity in ADHD-symptom trajectories remain unclear, mainly due to the scarcity of longitudinal neuroimaging studies of adolescent brain development. Therefore, a critical question remains unanswered: Do current medications influence symptom trajectories and their underlying neurodevelopmental processes toward sustained remission? A deeper understanding of these neurodevelopmental processes could facilitate the prediction of future symptom development, and inform novel intervention strategies that may alter symptom courses and promote sustained remission.
Methods:
In this study, we utilized two large longitudinal population-based cohorts (ABCD [n = 7,436] and IMAGEN [n = 109]) and three independent samples of clinically diagnosed ADHD patients (ADHD-200 [n = 263], ADHD-1000 [n = 742], and ADHD-Shanghai [n = 1,868]). These datasets collected genetic data, ADHD symptoms, structural MRI, ADHD medication information, and multiple functional assessments (school performance, sleep quality, pro-social behaviour, etc.) (Figure 1). First, in the ABCD study, we examined the relationship between ADHD symptom trajectories and distinct behavioural developmental profiles, as well as ADHD medication use. Next, we identified distinct neurodevelopmental signatures for each symptom trajectory between ages 10 and 12 and their key neurobiological processes. Third, we tested whether these neurodevelopmental signatures predict subsequent ADHD symptoms at age 13 and whether these findings could generalize to other independent clinical samples. This final step assesses the clinical relevance of the findings.
·Figure 1. Study design and workflow
Results:
Here, using a longitudinal cohort of adolescents (ABCD, n=7,436) to show that persistent, remitting, and emergent ADHD symptom trajectories correlated with persistent, improving, and worsening behavioral changes (e.g., school performance, sleep quality, and pro-social behaviour), respectively. Each trajectory had distinct neurodevelopmental signatures: faster cortical thinning (persistence), slower thinning (emergence), and faster subcortical expansion (remission). Slower cortical thinning in the right posterior cingulate cortex was associated with inattention symptom increase, while faster hippocampal volumetric expansion associated with inattention symptom decrease. The persistent and the emergent groups showed significant higher polygenic risk scores for ADHD as compared with the control group. The above findings were not affected by ADHD medication. Notably, these signatures associated with neurobiological processes, such as synaptic pruning and dopaminergic function, and enhanced ADHD symptom prediction at age 13 and generalized to young adults (age 23) in the IMAGEN cohort. More importantly, the hippocampal signature for remitting symptoms was replicated in IMAGEN and two clinical cohorts (ADHD-200, ADHD-1000). Given that baseline ADHD medication use was not significantly associated with the remitting trajectory, our findings suggest that current treatments may not facilitate sustained remission, highlighting the potential for new interventions.
Conclusions:
In summary, our findings highlight the importance of long-term clinical monitoring following the current pharmacotherapy for ADHD. The observed cortical thinning and hippocampal volumetric expansion as neurodevelopmental signatures for distinct trajectories of ADHD symptoms may inform new interventions, targeting these neurodevelopmental signatures to alter symptom trajectories and facilitate sustained remission.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems 2
Subcortical Structures
Keywords:
Attention Deficit Disorder
Cortex
STRUCTURAL MRI
Sub-Cortical
1|2Indicates the priority used for review
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