Poster No:
526
Submission Type:
Abstract Submission
Authors:
Mihai Avram1, Aurore Menegaux2, Felix Müller3, Hannes Zaczek3, Alexandra Korda1, Helena Rogg1, Anna Becker3, Laura Ley3, Matthias Liechti3, Stefan Borgwardt1
Institutions:
1University of Lübeck, Lübeck, Germany, 2Technical University of Munich, Munich, Bayern, 3University Hospital Basel, Basel, Switzerland
First Author:
Co-Author(s):
Anna Becker
University Hospital Basel
Basel, Switzerland
Laura Ley
University Hospital Basel
Basel, Switzerland
Introduction:
Mounting evidence indicates that psychedelics like psilocybin and lysergic acid diethylamide (LSD) may be used as psychiatric medicines in the treatment of several mental disorders (1,2,3). While the most consistent findings from modern clinical studies indicate significant antidepressant potential for psilocybin1, recent findings also hint at LSD's antidepressant effects2. The clinical trial NCT03866252 directly investigated LSD as a therapeutic agent in the treatment of major depression (MDD) and compared the effects of two low (2 x 25μg) and two moderate-to-high doses (2 x 100μg or 200μg in the second session) with promising results. While it is unclear how LSD might induce antidepressant effects, increased neuroplasticity has been suggested as a possible candidate (4). Intriguingly, rapid-induced neuroplastic effects have been reported in white matter (WM) in healthy subjects following distinct interventions5. Changes in WM can be assessed with diffusion-tensor imaging (DTI) in vivo, which quantifies fractional anisotropy (FA), a summary measure of WM microstructure integrity, and mean diffusivity (MD), reflecting the average mobility of water molecules.
Methods:
The data used in this study were derived from the clinical trial NCT03866252, which evaluated 61 patients with MDD. Patients were randomly allocated to the low- (LD-LSD) or high-dose LSD group (HD-LSD). DTI data were available for 38 MDD patients, consisting of two sessions: pre- and post-intervention. DTI data were analyzed with FSL. Preprocessing steps included image distortion correction, eddy current and motion correction, and quality checks (visual inspection and quad/squad). Three patients were excluded following quality control. The remaining participants (N=35; 17 HD-LSD) did not differ in age (p=.36) or sex (p=.63). We used tract-based spatial statistics (TBSS) to quantify FA and MD. To evaluate group differences, we first used a 2-way mixed effect ANOVA (2 groups, 2 levels per subject – pre/post) to test for group-by-time interactions for each measure (i.e., FA, MD). Significant interactions were followed by two-sample t-tests based on the post-pre difference to identify the direction of change. Finally, post-intervention FA values were extracted from areas reflecting group differences and correlated with changes from baseline in the Inventory of Depressive Symptomatology (∆IDS-C, clinician-rated) and Beck's Depression Inventory (∆BDI) at 2, 6, and 12 weeks after the second intervention.
Results:
A 2-way mixed effect ANOVA demonstrated a significant group-by-time interaction for FA in areas covering parts of the internal and external capsule, sagittal stratum, and fornix/stria-terminalis. This analysis was followed by a two-sample t-test, which demonstrated increased post-intervention FA values in the HD-LSD group in the same areas. Next, we extracted FA values from the regions reflecting group differences from the post-intervention scans and correlated them with ∆IDS-C and ∆BDI, respectively, at 2, 6, and 12 weeks after the second intervention. Symptom relief was significantly associated with post-intervention FA-values at 2 (ΔIDS-C: r=-.51, p=.03; ΔBDI: r=-.67, p=.003), 6 (ΔIDS-C: r=-.53, p=.03; ΔBDI: r=-.43, p=.09), and 12 weeks post-intervention (ΔIDS-C: r=-.71, p=.002; ΔBDI: r=-.63, p=.009) in the HD-LSD group only. No significant correlations were found for the LD-LSD group.
Finally, the group-by-time interaction for MD was not significant.
Conclusions:
We investigated LSD-induced changes in DTI-derived measures reflecting white matter integrity in MDD patients. While we did not find significant changes in MD, we observed higher FA values after treatment in the HD-LSD group. Remarkably, the increase in FA correlated with symptom improvement at 2, 6, and 12 weeks after intervention. Results indicate that two moderate-to-high doses of LSD induce structural changes related to symptom relief in MDD. Such changes may reflect LSD-induced neuroplasticity.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity
Physiology, Metabolism and Neurotransmission :
Pharmacology and Neurotransmission 2
Keywords:
Affective Disorders
Plasticity
Psychiatric Disorders
Seretonin
White Matter
Other - Psychedelics
1|2Indicates the priority used for review
Provide references using author date format
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