A multimodal large language model for evidence-based autism spectrum disorder screening

Autism spectrum disorder (ASD) affects 1 in 31 US children, yet median age at diagnosis exceeds four years. Artificial intelligence pipelines that provide quantified diagnosis using easy to access observational data (e.g., home videos) could help with earlier diagnosis, and timely delivery of early treatments. We fine-tuned Gemini 2.5 Pro on 400 clinician-rated home videos with low-rank adaptation, training only on 30 behavioral features previously validated to produce reliable predictions when passed to various ML models. On 99 held-out children (49 ASD, 50 neurotypical), inter-rater reliability with clinicians (per-feature weighted Cohen's kappa) improved by 40% (p<0.001), with 27 of 28 evaluable features improving. As an emergent zero-shot capability, direct ASD diagnosis F1 improved by 53% (p<0.001), matching or exceeding clinician outcomes. Classifier-assisted pipelines using fine-tuned LLM-derived behavioral features matched clinician-scored inputs across all tested pathways and achieved 77% accuracy (95% CI: 68-85%) and an AUC of 86% (95% CI: 78-92%). Fine-tuned multimodal LLMs can serve as scalable behavioral feature extractors for use in autism assessment and diagnosis.

Automated ASD screening tools remain limited by single-architecture evaluations, axis-restricted assessment, and near-exclusive focus on adult cohorts, obscuring age-specific diagnostic patterns critical for early intervention. We introduce ASD-Bench, a systematic tabular benchmark evaluating ML, deep learning, and foundation model configurations across three age cohorts (children 1-11 yr, adolescents 12-16 yr, adults 17-64 yr) on four axes: predictive performance, calibration, interpretability, and adversarial robustness. Applied to a curated v3 dataset of 4,068 AQ-10 records, our benchmark spans classical models (XGBoost, AdaBoost, Random Forest, Logistic Regression), neural networks (MLP), deep tabular transformers (TabNet, TabTransformer, FT-Transformer), and TabPFN v2. We introduce the Heuristic Aggregate Penalty (HAP): a cost-sensitive metric penalising false negatives more heavily and incorporating cross-validation variance for deployment stability. Adult classification yields high performance (10/17 models achieve perfect F1 and AUC), while adolescents present a harder task (F1 ceiling 0.837 vs. 0.915 for children). Feature hierarchies shift across cohorts: A9 (social motivation) dominates for children, A5 (pattern recognition) leads for adolescents, and adults exhibit a flatter importance profile consistent with developmental social masking. Accuracy and calibration are dissociated: AdaBoost achieves F1=1.000 on adults with ECE=0.302, confirming single-metric evaluation is insufficient for clinical AI. Cohort-specific deployment recommendations are provided. All findings should be interpreted as proof-of-concept evidence on questionnaire-derived labels rather than clinically validated diagnostic performance.

Characteristic linguistic behaviors associated with Social Language Disorder (SLD) in autism spectrum disorder, including echoic repetition, pronoun displacement, and stereotyped media quoting, are largely absent from spontaneous conversation and only emerge under specific conversational conditions. In structured clinical assessments, this latency means that questioning strategy selection is a critical yet underappreciated determinant of how much diagnostic information a conversation yields. Whether large language models (LLMs) can be guided to proactively select questioning strategies that systematically surface these latent traits remains largely unexplored. Here we present TPA (Think, Plan, Ask), a proactive multi-agent dialogue framework applied to the language assessment component of the Autism Diagnostic Observation Schedule Module 4 (ADOS-2), in which a doctor agent explicitly reasons about which traits remain unobserved before selecting a clinically grounded strategy and generating a targeted question. A patient agent grounded in real ADOS-2 clinical data enables reproducible evaluation without real patient participation, validated across three independent experiments confirming adequate fidelity to real patient language. Evaluated on 484 episodes from 35 patients, TPA outperforms six competitive dialogue planning baselines across all primary metrics, achieving 82.1% SLD trait coverage, 16.6% higher than automated replay of real clinical dialogues conducted by trained clinicians (65.5%), with substantially greater per-turn diagnostic efficiency (AUCC: 0.628 vs. 0.458, absolute gain +0.170). These results demonstrate that proactive questioning strategy selection substantially improves the efficiency of automated SLD trait assessment, with direct implications for scalable AI-assisted clinical screening.