OBJECTIVE Conceptual similarities between depressive and negative symptoms complicate biomarker and intervention development. This study employed a data-driven approach to delineate the neural circuitry underlying depressive and negative symptoms in schizophrenia spectrum disorders (SSDs). METHODS Data from three studies were analyzed (157 participants with SSDs) to assess brain-behavior relationships: two neuroimaging studies and a randomized trial of repetitive transcranial magnetic stimulation (rTMS). Partial least squares correlation (PLSC) was used to investigate associations between resting-state functional connectivity and depressive and negative symptoms. Secondary analyses of rTMS trial data (active, N=37; sham, N=33) were used to assess relationships between PLSC-derived symptom profiles and treatment outcomes. RESULTS PLSC identified three latent variables (LVs) relating functional brain circuitry with symptom profiles. LV1 related a general depressive symptom factor with positive associations between and within the default mode network (DMN), the frontoparietal network (FPN), and the cingulo-opercular network (CON). LV2 related negative symptoms (no depressive symptoms) via negative associations, especially between the FPN and the CON, but also between the DMN and the FPN and the CON. LV3 related a guilt and early wakening depression factor via negative rather than positive associations with the DMN, FPN, and CON. The secondary visual network had a positive association with general depressive symptoms and negative associations with guilt and negative symptoms. Active (but not sham) rTMS applied bilaterally to the dorsolateral prefrontal cortex (DLPFC) reduced general depressive but not guilt-related or negative symptoms. CONCLUSIONS The results clearly differentiate the neural circuitry underlying depressive and negative symptoms, and segregated across the two-factor structure of depression in SSDs. These findings support divergent neurobiological pathways of depressive symptoms and negative symptoms in people with SSDs. As treatment options are currently limited, bilateral rTMS to the DLPFC is worth exploring further for general depressive symptoms in people with SSDs.

中文翻译：

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精神分裂症谱系障碍中抑郁症状的神经回路和治疗靶向。


目的 抑郁症状和阴性症状之间的概念相似性使生物标志物和干预开发复杂化。本研究采用数据驱动的方法来描述精神分裂症谱系障碍 （SSD） 中抑郁和阴性症状背后的神经回路。方法 分析了来自三项研究 （157 名患有 SSD 的参与者） 的数据以评估大脑与行为的关系：两项神经影像学研究和一项重复经颅磁刺激 （rTMS） 的随机试验。偏最小二乘相关 （PLSC） 用于研究静息态功能连接与抑郁和阴性症状之间的关联。对 rTMS 试验数据 （阳性，N=37;假手术，N=33） 的二次分析用于评估 PLSC 衍生症状特征与治疗结果之间的关系。结果 PLSC 确定了三个潜在变量 （LVs），它们与功能性脑回路与症状特征相关。LV1 将一般抑郁症状因素与默认模式网络 （DMN） 、额顶网络 （FPN） 和扣带鳃盖网络 （CON） 之间和内部的正相关相关。LV2 通过负面关联（无抑郁症状）相关阴性症状（无抑郁症状），尤其是 FPN 和 CON 之间，以及 DMN 和 FPN 和 CON 之间。LV3 通过与 DMN、FPN 和 CON 的负相关而不是正相关，与内疚和早期觉醒抑郁因素相关。第二视觉网络与一般抑郁症状呈正相关，与内疚和阴性症状呈负相关。双侧应用于背外侧前额叶皮层 （DLPFC） 的主动（但不是假）rTMS 减轻了一般抑郁，但不是内疚相关或阴性症状。 结论 结果清楚地区分了抑郁和阴性症状背后的神经回路，并在 SSD 中分离了抑郁症的双因素结构。这些发现支持 SSD 患者抑郁症状和阴性症状的不同神经生物学途径。由于目前的治疗选择有限，对于 SSD 患者的一般抑郁症状，值得进一步探索 DLPFC 的双侧 rTMS。