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.

接触抗精神病药物以及某些首发疾病特征与精神分裂症早期更大的灰质（GM）缺陷有关。首发疾病特征是否影响大脑结构变化的长期进展仍有待探索。因此，我们评估了首发疾病特征和终生抗精神病药物使用与精神分裂症长期结构性脑 GM 变化之间的作用。来自 1966 年芬兰北部出生队列的精神分裂症患者（SZ，n=29）和非精神病对照组（n=61）在 34 岁（基线）和 43 岁（随访）时接受了结构 MRI。随访时，平均病程为19.8年。基于体素的形态测量用于评估预测因子对精神分裂症相关脑区纵向 GM 变化的影响。随访时，SZ 组的发病年龄 (AoO) 较小、累积抗精神病药物剂量较高和症状严重程度与较大的 GM 缺陷相关。首发疾病特征均与 9 年随访期间的纵向 GM 变化无关。我们得出的结论是，年轻的 AoO 和终生大量使用抗精神病药物可能会导致精神分裂症患者大脑结构变化的进展。除了 AoO 之外，其他首发疾病特征可能不会导致中年纵向 GM 变化。