Psychiatric disturbances may occur at the onset of multiple sclerosis. However, information on their outcome is lacking. Our objective was to document the characteristics of psychiatric symptoms at presentation of multiple sclerosis and to define the long-term evolution of psychiatric disturbances in these patients. Based on a clinical record analysis of patients with defined multiple sclerosis diagnosis and coming under the care of a university multiple sclerosis centre within the period 1997-2007, patients with both psychiatric and neurological symptoms at presentation were identified. Clinical data at onset and at last follow-up were considered. Among 682 evaluated patients, psychiatric disturbances were associated with multiple sclerosis onset in 16 cases (2.3%). Most patients (56%) presented with a mood disorder with clinical characteristics of a major depressive-like episode, five (32%) had psychotic symptoms. Initial psychiatric disturbances improved later than neurological symptoms, or never fully recovered, regardless of the concomitant use of psychotropic medications. In most of the subjects psychiatric disturbances tended to remain over the follow-up period and at last visit, after a mean follow-up of 7.6 years (+/-2.3), 14 subjects (87%) had a supplementary diagnosis of psychiatric illness. Psychiatric symptoms at onset of multiple sclerosis may be indicators of possible maintenance of psychiatric morbidity in a sizeable proportion of patients.