TY - JOUR
T1 - White matter alterations in Attention-Deficit/Hyperactivity Disorder (ADHD)
T2 - a systematic review of 129 diffusion imaging studies with meta-analysis
AU - Parlatini, Valeria
AU - Itahashi, Takashi
AU - Lee, Yeji
AU - Liu, Siwei
AU - Nguyen, Thuan T
AU - Aoki, Yuta
AU - Forkel, Stephanie
AU - Catani, Marco
AU - Rubia, Katya
AU - Zhou, Juan Helen
AU - Murphy, Declan
AU - Cortese, Samuele
N1 - Funding Information:
KR and SC were supported by the Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership (project ref: NIHR130077) and by the NIHR Programme Grant (NIHR203684), and SC by NIHR203035, NIHR128472, and RP-PG-0618-20003. KR and DGM were supported by the National Institute for Health Research (NIHR) and the UK Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) for Mental Health at South London and the Maudsley NHS Foundation Trust and Institute of Psychiatry, Psychology and Neuroscience, King’s College London. DGM was funded by two IMI initiatives (EU AIMS and AIMS-2-TRIALS) under grant agreements no.115300 and no. 777394. The design, management, analysis and reporting of the study are independent from the funders.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/7/21
Y1 - 2023/7/21
N2 - Aberrant anatomical brain connections in attention-deficit/hyperactivity disorder (ADHD) are reported inconsistently across diffusion weighted imaging (DWI) studies. Based on a pre-registered protocol (Prospero: CRD42021259192), we searched PubMed, Ovid, and Web of Knowledge until 26/03/2022 to conduct a systematic review of DWI studies. We performed a quality assessment based on imaging acquisition, preprocessing, and analysis. Using signed differential mapping, we meta-analyzed a subset of the retrieved studies amenable to quantitative evidence synthesis, i.e., tract-based spatial statistics (TBSS) studies, in individuals of any age and, separately, in children, adults, and high-quality datasets. Finally, we conducted meta-regressions to test the effect of age, sex, and medication-naïvety. We included 129 studies (6739 ADHD participants and 6476 controls), of which 25 TBSS studies provided peak coordinates for case-control differences in fractional anisotropy (FA)(32 datasets) and 18 in mean diffusivity (MD)(23 datasets). The systematic review highlighted white matter alterations (especially reduced FA) in projection, commissural and association pathways of individuals with ADHD, which were associated with symptom severity and cognitive deficits. The meta-analysis showed a consistent reduced FA in the splenium and body of the corpus callosum, extending to the cingulum. Lower FA was related to older age, and case-control differences did not survive in the pediatric meta-analysis. About 68% of studies were of low quality, mainly due to acquisitions with non-isotropic voxels or lack of motion correction; and the sensitivity analysis in high-quality datasets yielded no significant results. Findings suggest prominent alterations in posterior interhemispheric connections subserving cognitive and motor functions affected in ADHD, although these might be influenced by non-optimal acquisition parameters/preprocessing. Absence of findings in children may be related to the late development of callosal fibers, which may enhance case-control differences in adulthood. Clinicodemographic and methodological differences were major barriers to consistency and comparability among studies, and should be addressed in future investigations.
AB - Aberrant anatomical brain connections in attention-deficit/hyperactivity disorder (ADHD) are reported inconsistently across diffusion weighted imaging (DWI) studies. Based on a pre-registered protocol (Prospero: CRD42021259192), we searched PubMed, Ovid, and Web of Knowledge until 26/03/2022 to conduct a systematic review of DWI studies. We performed a quality assessment based on imaging acquisition, preprocessing, and analysis. Using signed differential mapping, we meta-analyzed a subset of the retrieved studies amenable to quantitative evidence synthesis, i.e., tract-based spatial statistics (TBSS) studies, in individuals of any age and, separately, in children, adults, and high-quality datasets. Finally, we conducted meta-regressions to test the effect of age, sex, and medication-naïvety. We included 129 studies (6739 ADHD participants and 6476 controls), of which 25 TBSS studies provided peak coordinates for case-control differences in fractional anisotropy (FA)(32 datasets) and 18 in mean diffusivity (MD)(23 datasets). The systematic review highlighted white matter alterations (especially reduced FA) in projection, commissural and association pathways of individuals with ADHD, which were associated with symptom severity and cognitive deficits. The meta-analysis showed a consistent reduced FA in the splenium and body of the corpus callosum, extending to the cingulum. Lower FA was related to older age, and case-control differences did not survive in the pediatric meta-analysis. About 68% of studies were of low quality, mainly due to acquisitions with non-isotropic voxels or lack of motion correction; and the sensitivity analysis in high-quality datasets yielded no significant results. Findings suggest prominent alterations in posterior interhemispheric connections subserving cognitive and motor functions affected in ADHD, although these might be influenced by non-optimal acquisition parameters/preprocessing. Absence of findings in children may be related to the late development of callosal fibers, which may enhance case-control differences in adulthood. Clinicodemographic and methodological differences were major barriers to consistency and comparability among studies, and should be addressed in future investigations.
UR - http://www.scopus.com/inward/record.url?scp=85165268993&partnerID=8YFLogxK
U2 - 10.1038/s41380-023-02173-1
DO - 10.1038/s41380-023-02173-1
M3 - Review article
SN - 1359-4184
JO - Molecular Psychiatry
JF - Molecular Psychiatry
ER -