Association of brain white matter microstructure with cognitive performance in major depressive disorder and healthy controls: a diffusion-tensor imaging study

Abstract

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.

Fig. 1. The general cognitive performance factor in HC and MDD patients.

MDD patients were divided into remitted, partially remitted and acute MDD by the SCID-I diagnoses. HC   healthy controls, MDD   major depressive disorder, SE   standard error.

Fig. 2. Healthy controls had higher fractional anisotropy (FA) values compared with acute depressive patients.

FA values are displayed at P_tfce-FWE < 0.05 onto the FMRIB58 template. Slice position is noted above the brain images.

Fig. 3. Association of fractional anisotropy (FA) and the general cognitive performance factor in major depressive disorder (MDD) patients and healthy controls (HC).

FA values were extracted with a threshold of P_tfce-FWE < 0.01 and displayed onto the FMRIB58 template in the x = −36, y = −9, z = 11 planes in MNI space. The scatterplot depicts mean FA values of the significant cluster with a threshold of P_tfce-FWE < 0.05.