Functional phenotypes in schizophrenia spectrum disorders: defining the constructs and identifying biopsychosocial correlates using data-driven methods.

IF 3 Q2 PSYCHIATRY
Sunny X Tang, Katrin Hänsel, Lindsay D Oliver, Erin W Dickie, Colin Hawco, Majnu John, Aristotle Voineskos, James M Gold, Robert W Buchanan, Anil K Malhotra
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Abstract

Functional impairments contribute to poor quality of life in schizophrenia spectrum disorders (SSD). We sought to (Objective I) define the main functional phenotypes in SSD, then (Objective II) identify key biopsychosocial correlates, emphasizing interpretable data-driven methods. Objective I was tested on independent samples: Dataset I (N = 282) and Dataset II (N = 317), with SSD participants who underwent assessment of multiple functioning areas. Participants were clustered based on functioning. Objective II was evaluated in Dataset I by identifying key features for classifying functional phenotype clusters from among 65 sociodemographic, psychological, clinical, cognitive, and brain volume measures. Findings were replicated across latent discriminant analyses (LDA) and one-vs.-rest binomial regularized regressions to identify key predictors. We identified three clusters of participants in each dataset, demonstrating replicable functional phenotypes: Cluster 1-poor functioning across domains; Cluster 2-impaired Role Functioning, but partially preserved Independent and Social Functioning; Cluster 3-good functioning across domains. Key correlates were Avolition, anhedonia, left hippocampal volume, and measures of emotional intelligence and subjective social experience. Avolition appeared more closely tied to role functioning, and anhedonia to independent and social functioning. Thus, we found three replicable functional phenotypes with evidence that recovery may not be uniform across domains. Avolition and anhedonia were both critical but played different roles for different functional domains. It may be important to identify critical functional areas for individual patients and target interventions accordingly.

Abstract Image

精神分裂症谱系障碍的功能表型:使用数据驱动方法定义结构并确定生物-心理-社会相关性。
功能障碍导致精神分裂症谱系障碍(SSD)患者生活质量低下。我们试图(目标一)定义精神分裂症谱系障碍的主要功能表型,然后(目标二)确定关键的生物-心理-社会相关因素,强调可解释的数据驱动方法。目标 I 在独立样本上进行了测试:数据集 I(N = 282)和数据集 II(N = 317)中的 SSD 参与者接受了多个功能领域的评估。根据功能对参与者进行分组。目标 II 在数据集 I 中进行了评估,从 65 个社会人口、心理、临床、认知和脑容量测量指标中识别出功能表型集群分类的关键特征。研究结果在潜在判别分析(LDA)和一vs.-rest二项式正则回归中得到了重复,以确定关键的预测因素。我们在每个数据集中发现了三个参与者集群,展示了可复制的功能表型:第 1 组--各领域功能较差;第 2 组--角色功能受损,但独立和社交功能部分保留;第 3 组--各领域功能良好。与之相关的主要因素包括逃避、失乐症、左侧海马体积以及情商和主观社会体验的测量。逃避似乎与角色功能更密切相关,而失乐症则与独立和社会功能更密切相关。因此,我们发现了三种可复制的功能表型,有证据表明不同领域的恢复可能并不一致。逃避和失乐症都很关键,但在不同的功能领域发挥着不同的作用。确定个体患者的关键功能领域并有针对性地进行干预可能非常重要。
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