People with Asperger's syndrome (AS) experience mental comorbidities, and behavioral symptoms that can deepen social isolation and handicaps. We compared the frequency of mental and behavioral symptoms, motor abnormality, and life history between adults with AS and those with no mental disorders but with disturbance of social functions and communication skills (ND) from our outpatient clinic. Participants with AS (n = 99) as compared with ND subjects (n = 63) showed significant higher rate of depressive mood, anxiety, unstable emotion, mood swings, oversensitivity to normal situation obsessive compulsive symptoms, persecutory idea, loss of energy, insomnia carelessness, restlessness, confusion in new environments, episodic agitation, inflexible adherence, egocentric behavior, self harm, circumscribed interest, poor lifestyle habits, non-athleticism, clumsiness, bulling at school, school non-attendance, social withdrawal, and lack of friendships. In AS, emotional instability and confusion in new environments might lead to social isolation. The findings demonstrated that individuals with AS experience greater social isolation and distress, as well as a wider range of mental and behavioral symptoms and disturbances of motor skills as compared to healthy subjects with disturbances of social functions and communication skills. These factors are interrelated and may be used as supplementary methods for differential diagnosis of AS from other conditions. (Contains 4 tables.)