Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that only rarely remits in adulthood. While several studies underlined differences between child and adult ADHD, the relationship between adult clinical presentation and early referral/treatment has been rarely investigated. In our study, 100 adults with ADHD were recruited and subdivided according to a history of referral to speciality care or treatment with methylphenidate (MPH) during childhood/adolescence. The early referral was associated with a history of disruptive behaviors during childhood/adolescence. Current ADHD symptoms were more pronounced in patients first referred during childhood/adolescence but never treated with MPH. Early MPH treatment was associated with lower rates of mood disorders and lower severity of emotional dysregulation at the time of assessment. Negative emotionality mediated the relationship between MPH treatment and mood disorders comorbidity. ADHD patients first referred during childhood/adolescence are characterized by more externalizing features than those first referred in adulthood. MPH treatment during the developmental age may have a role in preventing mood disorders in patients with ADHD, possibly by reducing emotional dysregulation.