Lewandowski Kathryn E, Blotner Julia, Yao Beier, Hechinger Rachel, Coleman Michael J, Shenton Martha E
Schizophrenia and Bipolar Disorder Program, McLean Hospital, Belmont, MA, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
World Psychiatry. 2025 Jun;24(2):260-266. doi: 10.1002/wps.21317.
Cognitive dysfunction is a core dimension in psychotic disorders and among the strongest predictors of disability and poor quality of life. Cognitive impairments are highly heterogeneous, and cross-sectional studies have consistently found evidence of distinct cognitive profiles both within diagnoses and transdiagnostically. Findings regarding the course of cognitive impairments over time have been mixed. We hypothesized that subgroups of patients in the early course of psychosis show distinct cognitive trajectories that can be identified using data-driven methods, and that these subgroups differ on clinical and functional outcomes over time. Persons with schizophrenia-spectrum disorders or mood disorders with psychosis in the early course of illness (N=127) were assessed using clinical, functional and cognitive measures at three timepoints: baseline, 8 and 16 months. Group-based trajectory modeling was used to identify cognitive subgroups, which were then compared on clinical and functional measures using multilevel models. We identified three distinct cognitive subgroups: an Impaired group, an Average group, and a High-Functioning group. Cognition was stable over the follow-up period in the Impaired and High-Functioning groups, whereas the Average group showed cognitive improvement. Groups did not differ in terms of diagnostic distribution, baseline clinical symptoms, and most baseline functional and demographic measures. However, over the follow-up, group membership predicted changes in negative symptoms, social functioning, and patient-reported outcomes, with the Impaired group showing the most severe illness course. We conclude that patients in the early course of psychosis show distinct cognitive trajectories that predict future symptoms and social functioning, despite presenting no clinical differences at baseline. These findings have implications for understanding biology-cognition associations, which may be related to heterogeneity; developing predictive models for clinical and functional outcomes; and personalizing treatment to support patients' cognitive, clinical and functional needs towards improving illness course.
认知功能障碍是精神障碍的一个核心维度，也是残疾和生活质量差的最强预测因素之一。认知障碍具有高度异质性，横断面研究一致发现，在诊断范围内和跨诊断情况下都有明显不同认知特征的证据。关于认知障碍随时间变化过程的研究结果不一。我们假设，处于精神病早期病程的患者亚组表现出不同的认知轨迹，这些轨迹可以通过数据驱动的方法识别，并且这些亚组在随时间变化的临床和功能结局方面存在差异。对疾病早期病程中的精神分裂症谱系障碍或伴有精神病性症状的心境障碍患者（N = 127）在三个时间点进行了临床、功能和认知测量：基线、8个月和16个月。基于组的轨迹模型用于识别认知亚组，然后使用多级模型对这些亚组在临床和功能测量方面进行比较。我们确定了三个不同的认知亚组：受损组、平均组和高功能组。在随访期间，受损组和高功能组的认知功能保持稳定，而平均组的认知功能有所改善。各组在诊断分布、基线临床症状以及大多数基线功能和人口统计学测量方面没有差异。然而，在随访过程中，亚组归属预测了阴性症状、社会功能和患者报告结局的变化，受损组显示出最严重的病程。我们得出结论，尽管在基线时没有临床差异，但处于精神病早期病程的患者表现出不同的认知轨迹，这些轨迹可预测未来的症状和社会功能。这些发现对于理解可能与异质性相关的生物学 - 认知关联、开发临床和功能结局的预测模型以及使治疗个性化以满足患者的认知、临床和功能需求从而改善病程具有重要意义。
