Cognitive deficits are central attendant symptoms of major depressive disorder (MDD) with a crucial impact in patients’ everyday life. Thus, it is of particular clinical importance to understand their pathophysiology. The aim of this study was to investigate a possible relationship between brain structure and cognitive performance in MDD patients in a well-characterized sample. N = 1007 participants (N_MDD = 482, healthy controls (HC): N_HC = 525) were selected from the FOR2107 cohort for this diffusion-tensor imaging study employing tract-based spatial statistics. We conducted a principal component analysis (PCA) to reduce neuropsychological test results, and to discover underlying factors of cognitive performance in MDD patients. We tested the association between fractional anisotropy (FA) and diagnosis (MDD vs. HC) and cognitive performance factors. The PCA yielded a single general cognitive performance factor that differed significantly between MDD patients and HC (P < 0.001). We found a significant main effect of the general cognitive performance factor in FA (P_tfce-FWE = 0.002) in a large bilateral cluster consisting of widespread frontotemporal-association fibers. In MDD patients this effect was independent of medication intake, the presence of comorbid diagnoses, the number of previous hospitalizations, and depressive symptomatology. This study provides robust evidence that white matter disturbances and cognitive performance seem to be associated. This association was independent of diagnosis, though MDD patients show more pronounced deficits and lower FA values in the global white matter fiber structure. This suggests a more general, rather than the depression-specific neurological basis for cognitive deficits.

认知缺陷是重度抑郁症 (MDD) 的主要伴随症状，对患者的日常生活具有至关重要的影响。因此，了解它们的病理生理学具有特殊的临床意义。本研究的目的是在一个特征明确的样本中调查 MDD 患者的大脑结构与认知表现之间的可能关系。N  = 1007 名参与者（N _MDD  = 482，健康对照 (HC)：N _HC = 525) 是从 FOR2107 队列中选择的，用于这项采用基于区域的空间统计的扩散张量成像研究。我们进行了主成分分析 (PCA) 以减少神经心理学测试结果，并发现 MDD 患者认知表现的潜在因素。我们测试了分数各向异性 (FA) 与诊断（MDD 与 HC）和认知表现因素之间的关联。PCA 产生了一个单一的一般认知表现因素，在 MDD 患者和 HC 之间存在显着差异 ( P  < 0.001)。我们发现 FA 中一般认知表现因素的显着主效应 ( P _tfce-FWE = 0.002) 在一个由广泛的额颞叶联合纤维组成的大型双侧簇中。在 MDD 患者中，这种影响与药物摄入、合并症诊断的存在、既往住院次数和抑郁症状无关。这项研究提供了强有力的证据，证明白质障碍和认知能力似乎是相关的。这种关联独立于诊断，尽管 MDD 患者在整体白质纤维结构中表现出更明显的缺陷和更低的 FA 值。这表明认知缺陷有更普遍的而非抑郁症特有的神经学基础。