title: Sex disparities in substance abuse research: Evaluating 23 years of structural neuroimaging studies.
abstract: Sex differences in brain structure and clinical course of substance use disorders underscores the need to include women in structural brain imaging studies. The NIH has supported the need for research to address sex differences. We evaluated female enrollment in substance abuse structural brain imaging research and the methods used to study sex differences in substance effects.
  
  
  
  Structural brain imaging studies published through 2016 (n=230) were evaluated for number of participants by sex and substance use status and methods used to evaluate sex differences. Temporal trends in the numbers of participants by sex and substance use status were analyzed. We evaluated how often sex effects were appropriately analyzed and the proportion of studies that found sex by substance interactions on volumetric measures.
  
  
  
  Female enrollment increased over time, but remained significantly lower than male enrollment (p=0.01), with the greatest bias for alcohol and opiate studies. 79% of studies included both sexes; however, 74% did not evaluate sex effects or used an analytic approach that precluded detection of sex by substance use interactions. 85% of studies that stratified by sex reported different substance effects on brain volumes. Only 33% of studies examining two-way interactions found significant interactions, highlighting that many studies were underpowered to detect interactions.
  
  
  
  Although female participation in substance use studies of brain morphometry has increased, sex disparity persists. Studying adequate numbers of both sexes and employing correct analytic approaches is critical for understanding sex differences in brain morphometric changes in substance abuse.
authors.affiliation: Department of Radiology, University of Colorado School of Medicine, Aurora, CO, USA; Departments of Health Systems, Management and Policy, University of Colorado School of Public Health, Aurora, CO, USA.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Lind
authors.affiliation: Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, CO, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Gutierrez
authors.affiliation: Department of Radiology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Yamamoto
authors.affiliation: Department of Radiology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Regner
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Sherry A
authors.initials: SA
authors.lastname: McKee
authors.affiliation: Department of Radiology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: jody.tanabe@ucdenver.edu.
authors.forename: Jody
authors.initials: J
authors.lastname: Tanabe
mesh_terms: D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000706:statistics & numerical data; D005260:Female; D054625:Healthcare Disparities / Q000706:statistics & numerical data*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D059906:Neuroimaging / Q000706:statistics & numerical data; D018579:Patient Selection; D012107:Research Design / Q000706:statistics & numerical data; D015983:Selection Bias; D063507:Sexism / Q000706:statistics & numerical data*; D019966:Substance-Related Disorders / Q000503:physiopathology*
keywords: Female inclusion; Grey matter volume; Sexual dimorphism; Structural brain imaging; Substance abuse