Neurodevelopmental markers in psychiatric disorders: A systematic review of facial dysmorphology assessed through 3D...

The current diagnosis of neurodevelopmental psychiatric disorders primarily relies on clinical symptoms, and the identification of reliable biomarkers remains an unmet clinical need. Emerging evidence shows that the face, due to shared embryological origin and genetic signalling pathways with the brain, may serve as an indirect marker of brain development and neurodevelopmental disorders. This systematic review aimed to evaluate the evidence supporting facial morphology as a biomarker for the diagnosis of autism spectrum disorders (ASD), schizophrenia (SZ) and bipolar disorder (BD), focusing on the use of 3D based-morphometric methods. It was conducted according to the PRISMA guidelines using the PubMed, PsycINFO and Web of Science databases. The search initially reported 630 articles, 523 were screened, and 14 were finally included after the application of inclusion criteria: i) case-control studies with cases primarily diagnosed with ASD, SZ, or BD; ii) facial dysmorphology assessment conducted with 3D image-based methods. The reviewed studies detected facial shape differences between patients and healthy controls in most conditions, validating the use of 3D image-based and morphometric methods as adequate tools to assess facial morphology variability. However, the findings were heterogeneous and variations in study design, sample size, and methodological approaches limit the comparability and generalisability of the results. Overall, the current evidence underscores the potential of facial morphology as a complementary marker for psychiatric conditions with a neurodevelopmental basis. However, the variability across studies highlights the need for further research using larger, well-characterised samples and standardised methodologies to clarify its clinical utility.