We analyzed longitudinal course of illness in schizophrenia until age 43 years, and its correlates to antipsychotic medication and cognition.

Northern Finland 1966 Birth Cohort Study has been followed serially since mid-pregnancy. Structural and functional MRI, cognitive, and clinical examinations were performed at ages 34 (73 schizophrenic psychoses, 104 controls) and 43 (63 schizophrenic psychoses, 192 controls); 40 cases and 75 controls participated in both surveys. Psychiatric outcomes have been ascertained through data linkage to a national case registers, hospital charts and clinical evaluations.

Prognosis of schizophrenia is heterogeneous: minority of individuals experience recovery, some achieve remission, but many are on disability pension, and excess mortality (especially suicides) is common. Long duration of untreated psychosis, early age of illness onset and presence of suicidal ideation associated with poorer long-term outcome. Both cases and non-psychotic controls show a small decline in verbal learning and memory, but the difference in decline is not significantly more pronounced in cases. Higher doses of antipsychotics at age 43-years associated to lower education and poorer clinical and functional outcomes, and high cumulative life-time use of antipsychotics associated to decrease of verbal learning and memory in 9-year follow-up.

Based on this naturalistic sample, midlife progression of schizophrenia may follow a variety of different trajectories. Poor clinical course is common but not necessary outcome. Compared to controls, more pronounced cognitive decline was not seen in schizophrenia cases. However, high doses of antipsychotics may relate to a decrease of verbal learning and memory.