Gray matter volume and microRNA levels in patients with attention-deficit/hyperactivity disorder

  • Liang-Jen Wang
  • Sung-Chou Li
  • Ho-Chang Kuo
  • Wen-Jiun Chou
  • Min-Jing Lee
  • Miao-Chun Chou
  • Huai-Hsuan Tseng
  • Chia-Fen Hsu
  • Sheng-Yu Lee
  • Wei-Che LinEmail author
Original Paper


Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder often characterized by gray matter (GM) volume reductions. MicroRNAs, which participate in regulating gene expression, potentially influence neurodevelopment. This study aimed to explore whether differential GM volume is associated with differential miRNA levels in ADHD patients. We recruited a total of 30 drug-naïve patients with ADHD (mean age 10.6 years) and 25 healthy controls (mean age 10.6 years) that underwent a single session of 3.0-T whole brain structural MRI scanning. RNA samples from the participants’ white blood cells were collected to identify the ΔCt values of three miRNAs (miR-30e-5p, miR-126-5p, and miR-140-3p) using the real-time quantitative reverse transcription polymerase chain reaction. In comparison to the control group, ADHD patients demonstrated a significantly lower GM volume in the cingulate gyrus, left middle temporal gyrus, right middle occipital gyrus, left fusiform gyrus, and significantly higher ΔCt values of miR-30e-5p, miR-126-5p, and miR-140-3p. In the ADHD group, the GM volume of cingulate gyrus and left fusiform gyrus was negatively correlated with the ΔCt values of miR-30e-5p, miR-140-3p. The GM volume of left fusiform gyrus was negatively correlated to ADHD behavioral symptoms. Using structural equation modeling (SEM), we observed that the effect of miR-140-3p on hyperactivity/impulsivity symptoms was mediated by left fusiform gyrus. Our findings support that GM volume reduction and miRNA increases may be biomarkers for ADHD in children and adolescents. Expression levels of miRNAs may affect the development of brain structures and further participate in the pathophysiology of ADHD.


ADHD Brain imaging Epigenetic miRNA Cortex 



The authors would like to thank Professor Wei-Tsun Soong for granting us the use of the Chinese version of the K-SADS.

Author contribution

LJW participated in study design, patient recruitment, reviewing references, and drafting the manuscript. SCL participated in study design, executed the miRNA analyses and interpreting the data. HCK, MJL, MCC, and WJC participated in data collection and patient recruitment. SYL drafted and revised the manuscript. HHT and CFH participated in protocol development and brain imaging data analyses. WCL participated in study design, brain imaging data analyses, draft and revised the manuscript. All the authors read and approved the final manuscript and contributed to the drafting and revising of the paper.


This work was supported by Grant from Chang Gung Memorial Hospital Research Project (CMRPG8E1451) and the Taiwan Ministry of Science and Technology (MOST 104-2314-B-182A-032 and MOST 105-2314-B-182A-054 -MY2 to LJ Wang, and MOST 106-2314-B-182A-031–MY2 to WC Lin).

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.

Supplementary material

406_2019_1032_MOESM1_ESM.xlsx (30 kb)
Supplementary material 1 (XLSX 30 kb)
406_2019_1032_MOESM2_ESM.doc (78 kb)
Supplementary material 2 (DOC 77 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
  2. 2.Department of Chinese MedicineChang Gung UniversityTaoyuanTaiwan
  3. 3.Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
  4. 4.Department of Pediatrics, Kaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
  5. 5.Kawasaki Disease CenterKaohsiung Chang Gung Memorial HospitalKaohsiungTaiwan
  6. 6.Department of Psychiatry, National Cheng Kung University Hospital, College of MedicineNational Cheng Kung UniversityTainanTaiwan
  7. 7.Department of Psychology, Clinical Psychological RoomChung Shan Medical University HospitalTaichungTaiwan
  8. 8.Department of PsychiatryKaohsiung Veterans General HospitalKaohsiungTaiwan
  9. 9.Department of Psychiatry, College of Medicine, Graduate Institute of Medicine, School of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  10. 10.Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan

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