The extent to which neuroanatomical variability associated with substance involvement reflects pre-existing risk and/or consequences of substance exposure remains poorly understood. In the Adolescent Brain Cognitive DevelopmentSM (ABCD®) Study, we identify associations between global and regional differences in brain structure and early substance use initiation (i.e., occurring <15 years of age; nsanalytic=6,556-9,804), with evidence that associations precede initiation. Neurodevelopmental variability in brain structure may confer risk for substance involvement.

The authors have declared no competing interest.

This study was supported by R01DA54750 (RB, AA). Additional funding included: APM (T32DA015035), DAAB (K99AA030808), SEP (F31AA029934), AA (R01DA54750), RB (R01DA54750, R21AA027827, U01DA055367). Data for this study were provided by the Adolescent Brain Cognitive Development (ABCD) study which was funded by awards U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147 from the NIH and additional federal partners (https://abcdstudy.org/federal-partners.html).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive DevelopmentSM (ABCD®) Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged 9-10 and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/consortium_members/. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from http://dx.doi.org/10.15154/1520591 (ABCD Annual Release 3.0) and http://dx.doi.org/10.15154/8873-zj65 (ABCD Annual Release 5.0). DOIs can be found at https://nda.nih.gov/abcd/abcd-annual-releases.html.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive DevelopmentSM (ABCD®) Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged 9-10 and follow them over 10 years into early adulthood. The ABCD Study® is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/consortium_members/. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from http://dx.doi.org/10.15154/1520591 (ABCD Annual Release 3.0) and http://dx.doi.org/10.15154/8873-zj65 (ABCD Annual Release 5.0). DOIs can be found at https://nda.nih.gov/abcd/abcd-annual-releases.html.