The contribution of first-episode illness characteristics and cumulative antipsychotic usage to progressive structural brain changes over a long-term follow-up in schizophrenia

Exposure to antipsychotics as well as certain first-episode illness characteristics have been associated with greater gray matter (GM) deficits in the early phase of schizophrenia. Whether the first-episode illness characteristics affect the long-term progression of the structural brain changes remain unexplored. We therefore assessed the role of first-episode illness characteristics and life-time antipsychotic use in relation to long-term structural brain GM changes in schizophrenia. Individuals with schizophrenia (SZ, n = 29) and non-psychotic controls (n = 61) from the Northern Finland Birth Cohort 1966 underwent structural MRI at the ages of 34 (baseline) and 43 (follow-up) years. At follow-up, the average duration of illness was 19.8 years. Voxel-based morphometry was used to assess the effects of predictors on longitudinal GM changes in schizophrenia-relevant brain areas. Younger age of onset (AoO), higher cumulative antipsychotic dose and severity of symptoms were associated with greater GM deficits in the SZ group at follow-up. None of the first-episode illness characteristics were associated with longitudinal GM changes during 9-year follow-up period. We conclude that a younger AoO and high life-time antipsychotic use may contribute to progression of structural brain changes in schizophrenia. Apart from AoO, other first-episode illness characteristics may not contribute to longitudinal GM changes in midlife.