Poster No:
597
Submission Type:
Abstract Submission
Authors:
Susanne Meinert1, Anna-Lena Boller1, Tilo Kircher2, Udo Dannlowski3, Judith Alferink1
Institutions:
1University of Münster, Münster, NRW, 2Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Hesse, 3Institute for Translational Psychiatry, Münster, North Rhine Westphalia
First Author:
Co-Author(s):
Tilo Kircher
Department of Psychiatry and Psychotherapy, University of Marburg
Marburg, Hesse
Udo Dannlowski
Institute for Translational Psychiatry
Münster, North Rhine Westphalia
Introduction:
In major depressive disorder (MDD), white matter abnormalities and immunological influences are discussed in its pathogenesis. Studies have found altered fibre microstructure as measured by fractional anisotropy (FA) in the corpus callosum and superior longitudinal fasciculus in MDD (1). In addition, immune system imbalances are described in these patients (2). Inflammatory processes could exert neurotoxic influences on the fibre structure, which is why both pathophysiological processes are closely intertwined (3). Since differential immune responses in MDD should be most apparent when confronted with stress, it is not surprising that previous studies have already linked childhood maltreatment experiences with changes in fibre structure as well as inflammatory processes (1,4).
The aim of this study was to describe the interactions between childhood maltreatment, fibre structure, and the immune system.
Methods:
N=159 age- and sex-matched MDD and healthy controls (HC) from the FOR2107 consortium were analysed, half of whom were classified as maltreated. Maltreatment was defined as two Childhood Trauma Questionnaire (CTQ) subscales that exceed defined thresholds (5) (N=40 HC_CTQ-, N=40 HC_CTQ+, N=39 MDD_CTQ-, N=40 MDD_CTQ+). Four novel lymphocyte subtypes were combined using principal component analysis (KMO=.618, Bartlett-χ²(6)<.001). Factor loadings were compared between the diagnosis (MDD vs. HC) and maltreatment (yes vs. no) groups. Diffusion tensor imaging was collected for all participants. Using tract-based spatial statistics, FA was associated with lymphocyte factor loadings. Associations between FA and lymphocyte factor loadings were compared between diagnosis and maltreatment groups. All DTI analyses were performed in a region-of-interest (ROI) analysis in the corpus callosum and the superior longitudinal fasciculus (ptfce-FWE<.05), in addition to an exploratory whole-brain approach (ptfce-FWE<.10).
Results:
A lymphocyte factor was found (eigenvalue=1.99, 49.7%). The lymphocyte factor did not differ between MDD and HC (p=.217). However, there was a main effect of maltreatment (p=.026, η²=.032) and a diagnosis x maltreatment interaction (p=.015, η²=.038). While no difference was found in HC with or without maltreatment, MDD patients with adverse childhood experiences had fewer immune cells than those without such experiences. Moreover, the lymphocyte factor was negatively associated with FA (ptfce-FWE=.021) in the corpus callosum. Using the exploratory threshold, the corpus callosum was confirmed in addition to the corona radiata and the thalamic radiation in the whole-brain approach (ptfce-FWE=.076). No effects were found in the superior longitudinal fasciculus (ptfce-FWE=.084) and no diagnosis and/or maltreatment interactions were present.
Conclusions:
A negative association was found between the combination of novel lymphocyte counts and white matter microstructure of the corpus callosum. This association did not differ between MDD and HC or as a function of maltreatment status. Nevertheless, differences in lymphocyte count were evident between maltreated and nonmaltreated MDD. This could contribute to the heterogeneity of neurobiological findings in depressed patients. Future longitudinal and experimental studies should build on this work to use knowledge of immunological processes to initiate new therapeutic developments.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Novel Imaging Acquisition Methods:
Diffusion MRI 2
Keywords:
Affective Disorders
MRI
White Matter
1|2Indicates the priority used for review
Provide references using author date format
1. Meinert S, Repple J, Nenadic I, Krug A, Jansen A, Grotegerd D, et al. Reduced fractional anisotropy in depressed patients due to childhood maltreatment rather than diagnosis. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2019;44(12):2065–72.
2. Otte C, Gold SM, Penninx BWJH, Pariante CM, Etkin A, Fava M, et al. Major depressive disorder. Nature reviews Disease primers. 2016;2:16065.
3. O’Donovan A, Bahorik A, Sidney S, Launer LJ, Yaffe K. Relationships of inflammation trajectories with white matter volume and integrity in midlife. Brain, behavior, and immunity. 2021;91:81–8.
4. Osborn M, Widom CS. Do documented records and retrospective reports of childhood maltreatment similarly predict chronic inflammation? Psychological Medicine. 2020;50(14):2406–15.
5. Walker EA, Gelfand A, Katon WJ, Koss MP, Von Korff M, Bernstein D, et al. Adult health status of women with histories of childhood abuse and neglect. The American Journal of Medicine. 1999 Oct;107(4):332–9.