Emerging biomarkers in autism spectrum disorder: a systematic review

Abstract

Autism spectrum disorder (ASD) affects approximately 2% of children in the United States (US) yet its etiology is unclear and effective treatments are lacking. Therapeutic interventions are most effective if started early in life, yet diagnosis often remains delayed, partly because the diagnosis of ASD is based on identifying abnormal behaviors that may not emerge until the disorder is well established. Biomarkers that identify children at risk during the pre-symptomatic period, assist with early diagnosis, confirm behavioral observations, stratify patients into subgroups, and predict therapeutic response would be a great advance.Here we underwent a systematic review of the literature on ASD to identify promising biomarkers and rated the biomarkers in regards to a Level of Evidence and Grade of Recommendation using the Oxford Centre for Evidence-Based Medicine scale. Biomarkers identified by our review included physiological biomarkers that identify neuroimmune and metabolic abnormalities, neurological biomarkers including abnormalities in brain structure, function and neurophysiology, subtle behavioral biomarkers including atypical development of visual attention, genetic biomarkers and gastrointestinal biomarkers. Biomarkers of ASD may be found prior to birth and after diagnosis and some may predict response to specific treatments.Many promising biomarkers have been developed for ASD. However, many biomarkers are preliminary and need to be validated and their role in the diagnosis and treatment of ASD needs to be defined. It is likely that biomarkers will need to be combined to be effective to identify ASD early and guide treatment.

Fractionating autism based on neuroanatomical normative modeling

“…Autism is a neurodevelopmental condition marked by impairments in social communication and interaction, alongside restricted and repetitive behaviors and sensory atypicalities 1 . It is still diagnosed based on behavioral observations and no validated biomarkers are available which could support diagnosis, stratification, or clinical management 2 . Efforts to identify replicable cognitive and biological substrates of the condition have been hampered by the pronounced biological, developmental, and clinical heterogeneity of individuals with autism 3 – 7 .…”

Comorbidity Matters: Social Visual Attention in a Comparative Study of Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder and Their Comorbidity

“…Recently, patterns of visual social attention which were obtained through gaze behavior were associated with caregiver-reported measures of social communication used in clinical trials (19). Thus, gaze measurements, as presented in our study, could serve as biomarkers for early diagnosis, monitoring and further care interventions as recommended (47).…”

“…Eye tracking measurements represent accurate, reproduceable measures that might serve as potential objective indications of medical states in order to predict the incidence and early diagnosis of a disorder as well as monitor outcomes of interventions (46). Regarding ASD, visual attention to social relevant stimuli has been recently suggested as a promising early behavioral biomarker (47). In addition, considering the high comorbidity of the ASD and ADHD and their suggested aetiological and biological overlap (48), comparisons between all respective clinical groups are necessary for the development of such valid biomarkers.…”

Mentally Sick or Not—(Bio)Markers of Psychiatric Disorders Needed

“…A new EEG-based diagnostic test (NEBA: Neuro-psychiatric EEG-based Assessment Aid) can be useful in ADHD [18]. In autism, there are found some potential physiological biomarkers that identify neuroimmune and metabolic abnormalities (methylation-redox, acyl-carnitine/amino-acids), neurological biomarkers pointing on abnormalities in brain structure (extra-axial fluid), on function and neurophysiology (EEG N170, mu rhythm, gamma band), on magnetoencephalography (MEG) auditory oscillations, and subtle behavioral biomarkers including atypical development of visual attention, as well as some genetic (single nucleotide polymorphisms) and gastrointestinal biomarkers (zonulin) [19].…”