TY - JOUR
T1 - In Search of Biomarkers to Guide Interventions in Autism Spectrum Disorder
T2 - A Systematic Review
AU - Parellada, Mara
AU - Andreu-Bernabeu, Álvaro
AU - Burdeus, Mónica
AU - San José Cáceres, Antonia
AU - Urbiola, Elena
AU - Carpenter, Linda L.
AU - Kraguljac, Nina V.
AU - McDonald, William M.
AU - Nemeroff, Charles B.
AU - Rodriguez, Carolyn I.
AU - Widge, Alik S.
AU - State, Matthew W.
AU - Sanders, Stephan J.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - OBJECTIVE: The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials. METHODS: A systematic review of MEDLINE, Embase, and Scopus was conducted in April 2020. Seven criteria were applied to focus on original research that includes quantifiable response biomarkers measured alongside ASD symptoms. Interventional studies or human studies that assessed the correlation between biomarkers and ASD-related behavioral measures were included. RESULTS: A total of 5,799 independent records yielded 280 articles for review that reported on 940 biomarkers, 755 of which were unique to a single publication. Molecular biomarkers were the most frequently assayed, including cytokines, growth factors, measures of oxidative stress, neurotransmitters, and hormones, followed by neurophysiology (e.g., EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly heterogeneous, including in phenotypes, demographic characteristics, tissues assayed, and methods for biomarker detection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify biomarkers with large effect sizes. Reporting of individual-level values and summary statistics was inconsistent, hampering mega- and meta-analysis. Biomarkers assayed in multiple studies yielded mostly inconsistent results, revealing a "replication crisis." CONCLUSIONS: There is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review highlights methodological imperatives for ASD biomarker research necessary to make definitive progress: consistent experimental design, correction for multiple comparisons, formal replication, sharing of sample-level data, and preregistration of study designs. Systematic "big data" analyses of multiple potential biomarkers could accelerate discovery.
AB - OBJECTIVE: The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials. METHODS: A systematic review of MEDLINE, Embase, and Scopus was conducted in April 2020. Seven criteria were applied to focus on original research that includes quantifiable response biomarkers measured alongside ASD symptoms. Interventional studies or human studies that assessed the correlation between biomarkers and ASD-related behavioral measures were included. RESULTS: A total of 5,799 independent records yielded 280 articles for review that reported on 940 biomarkers, 755 of which were unique to a single publication. Molecular biomarkers were the most frequently assayed, including cytokines, growth factors, measures of oxidative stress, neurotransmitters, and hormones, followed by neurophysiology (e.g., EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly heterogeneous, including in phenotypes, demographic characteristics, tissues assayed, and methods for biomarker detection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify biomarkers with large effect sizes. Reporting of individual-level values and summary statistics was inconsistent, hampering mega- and meta-analysis. Biomarkers assayed in multiple studies yielded mostly inconsistent results, revealing a "replication crisis." CONCLUSIONS: There is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review highlights methodological imperatives for ASD biomarker research necessary to make definitive progress: consistent experimental design, correction for multiple comparisons, formal replication, sharing of sample-level data, and preregistration of study designs. Systematic "big data" analyses of multiple potential biomarkers could accelerate discovery.
KW - Autism Spectrum Disorder
KW - Biological Markers
KW - Clinical Drug Studies
KW - Clinical Trials
KW - Endophenotypes
KW - Pharmacodynamic Biomarkers
KW - Response Biomarkers
KW - Symptom Severity
KW - Translational Research
UR - http://www.scopus.com/inward/record.url?scp=85145425017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85145425017&partnerID=8YFLogxK
U2 - 10.1176/appi.ajp.21100992
DO - 10.1176/appi.ajp.21100992
M3 - Article
C2 - 36475375
AN - SCOPUS:85145425017
VL - 180
SP - 23
EP - 40
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
SN - 0002-953X
IS - 1
ER -
