In a prospective cohort design, we investigated: i) diagnostic stability of initially antipsychotic-naïve schizophrenia patients, ii) symptom severity including symptomatic remission, and iii) functional remission including full recovery.

We included 143 antipsychotic-naïve patients with first-episode schizophrenia or schizoaffective disorder. After 4–18 years, we clinically re-evaluated diagnosis, symptom severity and functioning for 70 patients. From the nationwide Danish registers, we extracted pragmatic outcome measures for 142 patients. We examined associations between baseline variables (age at diagnosis, sex, and premorbid intelligence) and long-term outcome status (symptomatic and functional remission).

At 4–18 years follow-up, 80% met the criteria for schizophrenia or schizoaffective disorder, however, despite the high diagnostic stability 53% met the criteria of symptomatic and/or functional remission. Symptomatic remission characterized 34% of the patients and was associated with female sex, better premorbid intelligence, and a younger age at schizophrenia diagnosis. Functional remission characterized 41% of the patients and 17% of patients met criteria for full recovery both of which were associated with female sex. The clinically re-evaluated patients did not differ from the drop-outs on key register-based variables.

We confirm the emerging evidence of a decreasing long-term diagnostic stability of schizophrenia, and a protective role of female sex. The association between premorbid intelligence and symptomatic remission underscores the pertinence of including cognitive deficits in the diagnostic category of schizophrenia. The association between younger age at diagnosis and symptomatic remission may reflect positive effects of early detection or a drift in the interpretation of the diagnostic classification system.