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Background <p>Attention deficit hyperactivity disorder (ADHD) is frequently accompanied by both internalizing and externalizing symptoms, yet the neuroanatomical underpinnings of these comorbidities remain unclear, particularly within thalamic subnuclei that serve as central hubs of regulatory control.</p> Methods <p>We analyzed 3D T1-weighted MRI data from 359 ADHD patients (mean age = 10.19 ± 2.94, 265 males) and 209 healthy controls (mean age = 10.12 ± 3.48, 137 males) in the Healthy Brain Network cohort. ADHD participants were categorized into three subgroups: ADHD-only (<i>n</i> = 168, mean age = 10.18 ± 3.25), ADHD with internalizing symptoms (<i>n</i> = 97; mean age = 10.61 ± 2.67), and ADHD with externalizing symptoms (<i>n</i> = 94; mean age = 9.78 ± 2.58). Each thalamic nucleus was segmented into 25 subregions using FreeSurfer. ANCOVA were employed to examine differences of thalamic volumes between ADHD patients and healthy controls and to assess the associations with clinical symptoms. Subsequently, volumetric alterations across distinct ADHD comorbidity groups were examined, followed by age-related effects on thalamic development.</p> Results <p>Compared to healthy controls (HC), ADHD patients exhibited larger pulvinar anterior volumes and reduced volumes in the ventral anterior magnocellular, reuniens (medial ventral), and anteroventral nuclei. Larger thalamic volume in some subregions was negatively correlated with Child Behavior Checklist (CBCL) subscale scores in ADHD patients. Compared to the externalizing subgroup and HC group, the internalizing subgroup showed smaller volume in the reuniens (medial ventral), central lateral, paracentral, and laterodorsal nuclei. Moreover, in adolescents, the internalizing subgroup exhibited significantly smaller parafascicular, central lateral, and laterodorsal thalamic nuclei volumes than the externalizing subgroup. Whereas, in children, ADHD-only subgroup (without internalizing/externalizing comorbidities) demonstrated a significantly larger lateral geniculate nucleus volume relative to the externalizing subgroup.</p> Conclusions <p>ADHD is characterized by alterations in thalamic subregions, with the comorbid internalizing group showing more pronounced abnormalities. Developmentally, these alterations shift from peripheral nuclei in childhood to central nuclei in adolescence, suggesting that thalamic subregional changes in comorbid ADHD may vary across developmental stages. These findings highlight the clinical and developmental relevance of thalamic subregion abnormalities in the heterogeneity of ADHD comorbidities.</p> Clinical trial number <p>Not applicable.</p>

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Differential alterations of thalamic subregions in children and adolescents with attention deficit hyperactivity disorder and comorbid internalizing/externalizing disorders

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月26日

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  • Yongheng Zhao,
  • Yihao Zhang,
  • Jiahui Chen,
  • Xiaoying Ma,
  • Linlin Zhang,
  • Lihong Wang,
  • Zhiyue Liu,
  • Mengna Zhu,
  • Yu Wang,
  • Xingxing Zhu,
  • Aihua Cao

摘要

Background

Attention deficit hyperactivity disorder (ADHD) is frequently accompanied by both internalizing and externalizing symptoms, yet the neuroanatomical underpinnings of these comorbidities remain unclear, particularly within thalamic subnuclei that serve as central hubs of regulatory control.

Methods

We analyzed 3D T1-weighted MRI data from 359 ADHD patients (mean age = 10.19 ± 2.94, 265 males) and 209 healthy controls (mean age = 10.12 ± 3.48, 137 males) in the Healthy Brain Network cohort. ADHD participants were categorized into three subgroups: ADHD-only (n = 168, mean age = 10.18 ± 3.25), ADHD with internalizing symptoms (n = 97; mean age = 10.61 ± 2.67), and ADHD with externalizing symptoms (n = 94; mean age = 9.78 ± 2.58). Each thalamic nucleus was segmented into 25 subregions using FreeSurfer. ANCOVA were employed to examine differences of thalamic volumes between ADHD patients and healthy controls and to assess the associations with clinical symptoms. Subsequently, volumetric alterations across distinct ADHD comorbidity groups were examined, followed by age-related effects on thalamic development.

Results

Compared to healthy controls (HC), ADHD patients exhibited larger pulvinar anterior volumes and reduced volumes in the ventral anterior magnocellular, reuniens (medial ventral), and anteroventral nuclei. Larger thalamic volume in some subregions was negatively correlated with Child Behavior Checklist (CBCL) subscale scores in ADHD patients. Compared to the externalizing subgroup and HC group, the internalizing subgroup showed smaller volume in the reuniens (medial ventral), central lateral, paracentral, and laterodorsal nuclei. Moreover, in adolescents, the internalizing subgroup exhibited significantly smaller parafascicular, central lateral, and laterodorsal thalamic nuclei volumes than the externalizing subgroup. Whereas, in children, ADHD-only subgroup (without internalizing/externalizing comorbidities) demonstrated a significantly larger lateral geniculate nucleus volume relative to the externalizing subgroup.

Conclusions

ADHD is characterized by alterations in thalamic subregions, with the comorbid internalizing group showing more pronounced abnormalities. Developmentally, these alterations shift from peripheral nuclei in childhood to central nuclei in adolescence, suggesting that thalamic subregional changes in comorbid ADHD may vary across developmental stages. These findings highlight the clinical and developmental relevance of thalamic subregion abnormalities in the heterogeneity of ADHD comorbidities.

Clinical trial number

Not applicable.