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Alterations of White Matter in Brain Tied to Cognitive Impairment
Alterations of white matter in the brain occur to a larger extent among patients with major depressive disorder (MDD) compared with healthy individuals, according to study results published in Lancet Psychiatry.
Cognitive deficits occur frequently in MDD and are known to be associated with worse disease outcomes. Although white matter microstructure has been linked to depressive recurrence and cognitive performance, longitudinal studies are needed to determine the underlying mechanisms and related measures of disease course.
Researchers of an observational, prospective, case-control study aimed to determine the link between white matter integrity and cognitive performance in patients with MDD vs those without psychiatric disorders over a period of 2 years.
Participants aged between 18 and 65 years of Caucasian ancestry were identified for the current analysis, using the German Marburg-Münster Affective Disorders Cohort Study (MACS). Using neuropsychologic tests, the researchers assessed clinical data and cognitive performance, at baseline and 2 years of follow-up. Diffusion-weighted imaging was also performed, using magnetic resonance imaging (MRI) scans.
Of 881 participants identified at baseline between 2014 and 2019, 418 (47%) had MDD (mean age, 36.8 years; women, 66%) and 463 were healthy individuals (mean age, 35.6 years; women, 64%). Follow-up was conducted at mean of 2.2 years, between 2016 and 2021.
In the depression-associated analysis, the researchers found that compared with healthy participants, patients with MDD, specifically acute depression, had worse scores on the neuropsychologic tests at all timepoints, indicating lower cognitive performance (P <.0001; sr²=0.056).
The researchers noted a significant association between diagnosis and time, with patients with MDD vs healthy control participants showing a greater decline in white matter integrity over time (P =.026; sr²=0.002). However, cognitive decline was associated with changes in white matter integrity over time across both groups (P <.0001; sr²=0.004). Cross-sectional analysis also showed that lower cognitive performance was linked to reduced white matter integrity at all timepoints.
In a mediation analysis, adverse disease course and changes in white matter integrity were found to be predictors of cognitive deficits (β=0.073; P =.0022 and β=0.071; P =.0040, respectively).
Limitations of the analysis included MDD symptoms being based on patient self-reports; potential confounding factors; and lack of fully accounting for clinical characteristics, such as medication use and comorbidities, which may have affected cognitive performance and white matter integrity.
“Our findings [emphasize] the crucial role of white matter microstructure and disease progression in depression-related cognitive dysfunction, making both priority targets for future treatment development,” the researchers concluded.
This study was funded by German Research Foundation (DFG). Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the authors’ disclosures.
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