The autism spectrum among transgender youth: default mode functional connectivity

John F. Strang, Gender and Autism Program, Children's National Hospital, 15245 Shady Grove Road, Suite 350, Rockville, MD 20850, USA.
Lucy S. McClellan, Division of Neuropsychology, Children's National Hospital, Washington, DC, USA.
Sufang Li, Department of Psychology, Georgetown University, Washington, DC, USA.
Allison E. Jack, Department of Psychology, George Mason University, Fairfax, VA, USA.
Gregory L. Wallace, Department of Speech, Language, & Hearing Sciences, George Washington University, Washington, DC, USA.
Goldie A. McQuaid, Department of Psychology, George Mason University, Fairfax, VA, USA.
Lauren Kenworthy, Departments of Pediatrics, Psychiatry, and Behavioral Sciences, George Washington University School of Medicine, Washington, DC, USA.
Laura G. Anthony, Department of Psychiatry and Behavioral Sciences, University of Colorado School of Medicine, Aurora, CO, USA.
Meng-Chuan Lai, Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada.
Kevin A. Pelphrey, Department of Neurology, University of Virginia Medical School, Charlottesville, VA, USA.
Alexandra E. Thalberg, Department of Biology, Georgetown University, Washington, DC, USA.
Eric E. Nelson, Center for Biobehavioral Health, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Jenny M. Phan, Division of Neuropsychology, Children's National Hospital, Washington, DC, USA.
Eleonora Sadikova, School of Education and Human Development, University of Virginia, Charlottesville, VA, USA.
Abigail L. Fischbach, Division of Neuropsychology, Children's National Hospital, Washington, DC, USA.
John Thomas, Falls Church Counseling, VA, USA.
Chandan J. Vaidya, Department of Psychology, Georgetown University, Washington, DC, USA.

Document Type

Journal Article

Publication Date

1-31-2023

Journal

Cerebral cortex (New York, N.Y. : 1991)

DOI

10.1093/cercor/bhac530

Keywords

Autistic; Gender diverse; Resting state

Abstract

The common intersection of autism and transgender identities has been described in clinical and community contexts. This study investigates autism-related neurophenotypes among transgender youth. Forty-five transgender youth, evenly balanced across non-autistic, slightly subclinically autistic, and full-criteria autistic subgroupings, completed resting-state functional magnetic resonance imaging to examine functional connectivity. Results confirmed hypothesized default mode network (DMN) hub hyperconnectivity with visual and motor networks in autism, partially replicating previous studies comparing cisgender autistic and non-autistic adolescents. The slightly subclinically autistic group differed from both non-autistic and full-criteria autistic groups in DMN hub connectivity to ventral attention and sensorimotor networks, falling between non-autistic and full-criteria autistic groups. Autism traits showed a similar pattern to autism-related group analytics, and also related to hyperconnectivity between DMN hub and dorsal attention network. Internalizing, gender dysphoria, and gender minority-related stigma did not show connectivity differences. Connectivity differences within DMN followed previously reported patterns by designated sex at birth (i.e. female birth designation showing greater within-DMN connectivity). Overall, findings suggest behavioral diagnostics and autism traits in transgender youth correspond to observable differences in DMN hub connectivity. Further, this study reveals novel neurophenotypic characteristics associated with slightly subthreshold autism, highlighting the importance of research attention to this group.

Department

Psychiatry and Behavioral Sciences

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