Time heals all wounds? A 2-year longitudinal diffusion tensor imaging study in major depressive disorder

Repple, Jonathan; Zaremba, Dario; Meinert, Susanne; Grotegerd, Dominik; Redlich, Ronny; Förster, Katharina; Dohm, Katharina; Hahn, Tim; Enneking, Verena; Leehr, Elisabeth J.; Böhnlein, Joscha; Dzvonyar, Fanni; Sindermann, Lisa; Winter, Nils R.; Goltermann, Janik; Kugel, Harald; Bauer, Jochen; Heindel, Walter; Arolt, Volker

doi:10.1503/jpn.180243

Cited by 10 publications

(5 citation statements)

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“…Repple et al examined the alterations of fractional anisotropy (FA), mean diffusivity, radial diffusivity and axial diffusivity in MDD patients throughout a 2-year treatment course. Patients with current depression showed higher mean diffusivity in the prefrontal lobe, which was dissipated at the remission phase (18). Based on these findings, white matter microstructural abnormalities seemed to be statedependent alterations fluctuating with depression symptoms in the pathogenesis of MDD.…”

Section: Introductionmentioning

confidence: 79%

State-Independent Microstructural White Matter Abnormalities in Major Depressive Disorder

et al. 2020

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Background: Even with continuous antidepressant treatment, residual symptoms and the risk of relapse can persist in remitted major depressive disorder (MDD) patients. Hence, having a clear recognition of the persistent abnormalities of the underlying neural substrate in MDD through a longitudinal investigation is of great importance.Methods: A total of 127 adult medication-free MDD patients with an acute depressive episode and 118 matched healthy controls (HCs) underwent diffusion tensor imaging. Over a 6-month treatment course, 62 remitted patients underwent a second scan. Remission was defined as a 24-item Hamilton Depression Rating Scale (HAMD 24 ) score ≤7 for at least two weeks. Diffusion tensor imaging was performed with a 3.0 T scanner. Differences in wholebrain fractional anisotropy (FA) between MDD patients and HCs were assessed by an independent t-test using gender, age, and education as covariates.Results: Significant FA reductions in the left insula, left middle occipital gyrus, right thalamus, left pallidum and left precuneus were observed in current MDD (cMDD) patients compared with HCs. Moreover, significant FA reductions in the left insula were observed in remitted (rMDD) patients compared to HCs. However, no significant differences in FA values were found when comparing cMDD and rMDD patients. Conclusions:The abnormalities in the insula showed state-independent characteristics, while the abnormalities in the middle occipital gyrus, thalamus, pallidum and precuneus seemed to be state-dependent impairments in MDD patients.

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Section: Introductionmentioning

confidence: 79%

State-Independent Microstructural White Matter Abnormalities in Major Depressive Disorder

et al. 2020

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“…We used the nonparametric permutation testing implemented in FSL's “randomize” with 5,000 permutations, to test for statistical significance. Threshold‐free cluster enhancement (TFCE; Smith & Nichols, 2009), a previously employed method (Repple et al, 2019; Repple, Karliczek, et al, 2019) to correct for multiple comparisons, allows estimation of cluster sizes corrected for the family‐wise error (FWE; p < .05, 5,000 permutations). MNI coordinates and cluster size at peak voxel were derived with FSL Cluster and the corresponding WM tract retrieved from the ICBM‐DTI‐81 white‐matter atlas (Pekar et al, 2007; Repple et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

Sleep duration is associated with white matter microstructure and cognitive performance in healthy adults

Grumbach

Martin

Meinert

et al. 2020

Human Brain Mapping

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Reduced sleep duration and sleep deprivation have been associated with cognitive impairment as well as decreased white matter integrity as reported by experimental studies. However, it is largely unknown whether differences in sleep duration and sleep quality might affect microstructural white matter and cognition. Therefore, the present study aims to examine the cross‐sectional relationship between sleep duration, sleep quality, and cognitive performance in a naturalistic study design, by focusing on the association with white matter integrity in a large sample of healthy, young adults. To address this, 1,065 participants, taken from the publicly available sample of the Human Connectome Project, underwent diffusion tensor imaging. Moreover, broad cognitive performance measures (NIH Cognition Toolbox) and sleep duration and quality (Pittsburgh Sleep Quality Index) were assessed. The results revealed a significant positive association between sleep duration and overall cognitive performance. Shorter sleep duration significantly correlated with fractional anisotropy (FA) reductions in the left superior longitudinal fasciculus (SLF). In turn, FA in this tract was related to measures of cognitive performance and was shown to significantly mediate the association of sleep duration and cognition. For cognition only, associations shift to a negative association of sleep duration and cognition for participants sleeping more than 8 hr a day. Investigations into subjective sleep quality showed no such associations. The present study showed that real‐world differences in sleep duration, but not subjective sleep quality are related to cognitive performance measures and white matter integrity in the SLF in healthy, young adults.

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“…To completely disentangle the effects of acute symptomatology and course of illness, future longitudinal studies are necessary. In small groups of MDD patients, longitudinal studies found either associations between fiber integrity changes over the follow-up period and depressive symptom changes (Bracht, Jones, Müller, Wiest, & Walther, 2015; Doolin et al, 2019) or no association with course of illness or symptom severity, respectively (Repple et al, 2019). The largest longitudinal study to date ( N = 18 959) underscores the importance of the longitudinal illness burden (Shen et al, 2019): Although decreased white matter microstructure was linked to depressive symptoms, the strongest association was found for the longitudinal progression of depressive symptoms in fronto-temporal association fibers.…”

Section: Discussionmentioning

confidence: 99%

White matter fiber microstructure is associated with prior hospitalizations rather than acute symptomatology in major depressive disorder

et al. 2020

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Background Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness. Methods A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects. Results Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF. Conclusions Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.

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Time heals all wounds? A 2-year longitudinal diffusion tensor imaging study in major depressive disorder

Cited by 10 publications

References 46 publications

State-Independent Microstructural White Matter Abnormalities in Major Depressive Disorder

State-Independent Microstructural White Matter Abnormalities in Major Depressive Disorder

Sleep duration is associated with white matter microstructure and cognitive performance in healthy adults

White matter fiber microstructure is associated with prior hospitalizations rather than acute symptomatology in major depressive disorder

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