Background: Autism Spectrum Disorder (ASD) is a complex and heterogeneous neurodevelopmental condition. Diagnosing ASD in adults, especially in milder forms, remains challenging due to camouflaging strategies, adaptive behaviors, and frequent psychiatric comorbidities. Despite increased awareness, there is a critical need to improve recognition and tailored interventions for adults with ASD. This study aims to examine the prevalence of psychiatric comorbidities among individuals diagnosed with ASD. Methods: This retrospective cross-sectional study examined 64 adults diagnosed with ASD (n = 29 females, 45.3%; age: range, 18–57 years; mean ± SD, 30.9 ± 8.92), who accessed two university hospital outpatient units in Rome between September 2023 and January 2025. All participants were assessed using the Autism Diagnostic Observation Schedule, Second Edition–Module 4 (ADOS-2). Psychiatric comorbidities were evaluated using clinical assessments and the Mini-International Neuropsychiatric Interview (M.I.N.I.) Plus. Results: All patients received an ASD diagnosis without intellectual disability. Forty-four (68.8%) presented with at least one psychiatric comorbidity, most commonly depressive (25.0%) and anxiety disorders (9.4%). Over half of the participants (57.4%) reported at least mild depressive symptoms, and 42.6% exhibited moderate to severe depressive levels. Conclusions: High rates of psychiatric comorbidities, particularly mood and anxiety disorders, were observed, underscoring the importance of comprehensive, multidisciplinary assessment and individualized interventions. Further research using larger samples and rigorous methodologies is warranted to better characterize the ASD phenotype in adults and guide targeted therapeutic strategies.

Background: Autism Spectrum Disorder (ASD) is a complex and heterogeneous neurodevelopmental condition. Diagnosing ASD in adults, especially in milder forms, remains challenging due to camouflaging strategies, adaptive behaviors, and frequent psychiatric comorbidities. Despite increased awareness, there is a critical need to improve recognition and tailored interventions for adults with ASD. Methods: We conducted a cross-sectional study involving 64 adults diagnosed with ASD at two university hospital outpatient units in Rome. All participants were assessed using the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). Psychiatric comorbidities were evaluated using clinical assessments and the Mini-International Neuropsychiatric Interview (M.I.N.I.) Plus. Results: The sample included 45.3% females, with a mean age of 30.9 years. All patients had Level 1 ASD without intellectual disability. Overall, 68.8% presented with at least one psychiatric comorbidity, most commonly depressive (25.0%) and anxiety disorders (9.4%). Over half of the participants (57.4%) reported at least mild depressive symptoms, and 42.6% exhibited moderate to severe levels. Conclusions: High rates of psychiatric comorbidities, particularly mood and anxiety disorders, were observed underscoring the importance of comprehensive, multidisciplinary assessment and individualized interventions. Further research using larger samples and rigorous methodologies is warranted to better characterize the ASD phenotype in adults and guide targeted therapeutic strategies.