In Search of Biomarkers to Guide Interventions in Autism Spectrum Disorder: A Systematic Review

Mara Parellada, Álvaro Andreu-Bernabeu, Mónica Burdeus, Antonia San José Cáceres, Elena Urbiola, Linda L. Carpenter, Nina V. Kraguljac, William M. McDonald, Charles B. Nemeroff, Carolyn I. Rodriguez, Alik S. Widge, Matthew W. State, Stephan J. Sanders

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations


Objective: The aim of this study was to catalog and evaluate heterogeneous, including in phenotypes, demographic char-response biomarkers correlated with autism spectrum disacteristics, tissues assayed, and methods for biomarker deorder (ASD) symptoms to improve clinical trials. tection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify bio-Methods: A systematic review of MEDLINE, Embase, and markers with large effect sizes. Reporting of individual-level Scopus was conducted in April 2020. Seven criteria were values and summary statistics was inconsistent, hampering applied to focus on original research that includes quantifimega- and meta-analysis. Biomarkers assayed in multiple able response biomarkers measured alongside ASD sympstudies yielded mostly inconsistent results, revealing a toms. Interventional studies or human studies that assessed “replication crisis.” the correlation between biomarkers and ASD-related behavioral measures were included. Conclusions: There is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review Results: A total of 5,799 independent records yielded 280 arhighlights methodological imperatives for ASD biomarker ticles for review that reported on 940 biomarkers, 755 of which research necessary to make definitive progress: consistent were unique to a single publication. Molecular biomarkers experimental design, correction for multiple comparisons, were the most frequently assayed, including cytokines, formal replication, sharing of sample-level data, and pregrowth factors, measures of oxidative stress, neurotransregistration of study designs. Systematic “big data” analyses of mitters, and hormones, followed by neurophysiology (e.g., multiple potential biomarkers could accelerate discovery. EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly Am J Psychiatry 2023; 180:23–40; doi: 10.1176/appi.ajp.21100992

Original languageEnglish (US)
Pages (from-to)23-40
Number of pages18
JournalAmerican Journal of Psychiatry
Issue number1
StatePublished - Jan 2023

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Funding Information:
Although some have contended that the turnover of health personnel in rural areas is unavoidable and that the focus should be on the continuity of services, rather than on the continuity of the individual practitioner, 43 this assessment should not be meant to imply that any factor constitutes an insurmountable barrier to successfully staffing adequate numbers of nursing personnel. In many instances, creative and well-implemented recruitment and retention programs can conceivably overcome even the most seemingly insurmountable barriers faced by rural providers. 36, 44 We should help those states that contain significant nurse shortage counties to address the problem by formulating strategies that extend beyond merely nurses and nursing. Policies aimed at easing the shortage of nursing personnel in rural areas must recognize the structural barriers that inhibit rural settings from attracting and retaining their fair share of available nurses. Equally serious attention must be paid to related rural issues, such as economic development, the shortage of other health care providers, hospital viability, Medicare/Medicaid reimbursements, and vulnerable populations. Only when these related factors are realized and addressed in rural areas will it truly be possible to speak of the nursing shortage in the past tense. • Supported, in part, by funding from the Office of Rural Health Policy, U.S. Department of Health and Human Services (Grant No. CSR000005"0 I-0).


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