ORCID Profile
0000-0002-4006-010X
Current Organisation
Medical University of Vienna
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Cold Spring Harbor Laboratory
Date: 29-04-2022
DOI: 10.1101/2022.04.29.22274480
Abstract: Alterations in gray matter (GM) and monoamine oxidase A (MAO-A) distribution across the brain have been found in various neuropsychiatric conditions. MAO-A catalyzes the oxidative degradation of various monoamines and is thus implicated in neuroplastic processes that influence GM density (GMD) and microstructure (GMM) of the brain. Sex-specific differences in these patterns are well documented, however studying the long-term effects of certain sex steroids on the brain are limited due to hormonal fluctuations under naturalistic conditions. Due to the exact monitoring of plasma hormone levels and sex steroid intake, transgender in iduals undergoing gender-affirming hormone therapy represent a valuable cohort to investigate such changes of GM and concomitant MAO-A density. Here, we investigated the effects of long-term gender-affirming hormone therapy over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men were recruited. All participants underwent two MRI scans in a longitudinal design. PET scans using [ 11 C]harmine were performed before each MRI session in a subset of 35 in iduals. Between baseline and follow-up imaging, transgender subjects underwent gender-affirming hormone therapy. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: p FWE+Bonferroni 0.025). In terms of MAO-A distribution volume, no significant effects were found. The present results are indicative of a reliable influence of gender-affirming hormone therapy on GMD and GMM following an interregional pattern. Nevertheless, future studies with larger s le sizes are needed to further investigate the relationship between sex steroids, gray matter alterations and MAO-A density.
Publisher: Cold Spring Harbor Laboratory
Date: 21-02-2022
DOI: 10.1101/2022.02.17.22271118
Abstract: Theta burst stimulation (TBS) belongs to one of the biological antidepressant treatment options. When applied bilaterally, excitatory intermittent TBS (iTBS) is commonly targeted to the left and inhibitory continuous TBS (cTBS) to the right dorsolateral prefrontal cortex. TBS was shown to influence neurotransmitter systems, while iTBS is thought to interfere with glutamatergic circuits and cTBS to mediate GABAergic neurotransmission. We aimed to expand insights in the therapeutic effects of TBS on the GABAergic and glutamatergic system utilizing 3D-multivxovel magnetic resonance spectroscopy imaging (MRSI) in combination with a novel surface-based MRSI analysis approach to investigate changes of cortical neurotransmitter levels in patients with treatment resistant depression (TRD). Twelve TRD patients (5 female, mean age±SD=35±11 years) completed paired MRSI measurements, using a GABA-edited 3D-multivoxel MEGA-LASER sequence, before and after three weeks of bilateral TBS treatment. Changes in cortical distributions of GABA+/tNAA (GABA+macromolecules relative to total N-acetylaspartate) and Glx/tNAA (Glx=mixed signal of glutamate and glutamine), were investigated in a surface-based region-of-interest (ROI) analysis approach. ANCOVAs revealed a significant increase in Glx/tNAA ratios in the left caudal middle frontal area (p corr .=0.046, F=13.292), an area targeted by iTBS treatment. Whereas, contralateral treatment with cTBS evoked no alterations in glutamate or GABA concentrations. This study demonstrates surface-based adaptions in the stimulation area to the glutamate metabolism after excitatory iTBS but not after cTBS, using a novel surface-based analysis of 3D-MRSI data. The reported impact of facilitatory iTBS on glutamatergic neurotransmission provides further insight into the neurobiological effects of TBS in TRD.
Publisher: Cold Spring Harbor Laboratory
Date: 15-01-2021
DOI: 10.1101/2021.01.15.426779
Abstract: Learning-induced neuroplastic changes, further modulated by content and setting, are mirrored in brain functional connectivity (FC). In animal models, serotonergic agents were shown to facilitate neuroplasticity. This is especially prominent during emotional relearning, such as fear extinction, which may translate to clinical improvements in human patients. To investigate this assumption, 99 healthy subjects underwent six weeks of emotional or non-emotional learning and subsequent relearning. Resting-state functional magnetic resonance imaging was performed before and after the learning phases to investigate changes in FC. During relearning, subjects received either a daily dose of the selective serotonin reuptake inhibitor (SSRI) escitalopram or placebo. Escitalopram intake modulated FC changes in a network comprising Broca’s area, the medial prefrontal cortex, the right inferior temporal and left lingual gyrus. More specifically, escitalopram increased the bidirectional connectivity between medial prefrontal cortex and lingual gyrus for non-emotional and additionally the connectivity from medial prefrontal cortex to Broca’s area for emotional relearning. The context-dependence of these effects supports the assumption that SSRIs in clinical practice might improve neuroplasticity rather than psychiatric symptoms per se. Correlations with learning behavior further point towards a relationship with extinction processes in relearning. These results demonstrate that escitalopram intake during relearning results in content-dependent network adaptations and support the conclusion that enhanced neuroplasticity might be the major underlying mechanism also in humans. Beyond expanding the complexities of learning, these findings emphasize the influence of external factors on serotonin-facilitated neuroplasticity of the human brain.
Publisher: Oxford University Press (OUP)
Date: 31-07-2013
Publisher: Elsevier BV
Date: 08-2021
No related grants have been discovered for David Fiellin.