Work

Differential effect of cannabis in gray matter extracellular free-water in early psychosis subjects versus controls

Year: 2022

Type: article

Abstract: Background: Serotonin reuptake inhibitors (SSRIs) have been a mainstay in the treatment of major depressive disorder for decades, yet the mechanisms behind their antidepressant effect still have not fully been uncovered.The idea that serotonin (5-HT) plays a considerable role in neuroplasticity and -genesis offers a partial explanation for these effects.Diffusion-weighted imaging (DWI) is rarely applied in cortical grey matter (GM), but a recent study [1] found regionspecific changes in multiple GM diffusivity measures (such as fractional anisotropy and mean diffusivity) in a rat model as a result of ketamine administration, which shares downstream effectors with SSRIs in neurotrophins and tropomyosin receptor kinase B. If structural remodelling in regions involved in depression causes SSRIs' antidepressant effects, the analysis of cortical diffusivity parameters might allow us to investigate these processes, as microstructural GM reorganisation has been explored through changes in mean diffusivity (MD) in previous publications [2].We aimed to achieve this by measuring changes in MD in healthy controls over a three-week course of escitalopram during memorisation training.Methods: 76 (44 female, mean age: 25.6 Æ 5.0) healthy participants performed six weeks of daily learning of either Chinese characters and unrelated German nouns or pairs of faces in a longitudinal, double-blind, placebo-controlled study.Magnetic resonance imaging (MRI) measurements were performed at three and six weeks, respectively.After three weeks of training, association pairs were randomly shuffled into new combinations, which participants had to (re)learn for another three weeks, while also receiving either 10 mg/day of escitalopram (Cipralex®, Lundbeck A/S) or placebo.Structural changes in cortical grey matter, measured by changes in MD were calculated and DWI data was processed in accordance with the optimised pipeline described in [3].Medication x task x time, as well as medication x time interactions were estimated via repeated measures ANOVA (pFWE+Bonferroni < 0.025).Results: Both three-way (task x medication x time) and two-way (medication x time) interactions did not show any significant effects after correction for multiple testing (pFWE+Bonferroni > 0.3).Additionally, an exploratory uncorrected analysis did not provide evidence of significant differences between groups.Conclusion: The results of our analysis have shown no significant difference in cortical MD between the escitalopram and placebo groups over time.Previously published results from our group, based on the same project, similarly did not find changes in various diffusivity measures subsequent to (re)learning and escitalopram intervention in white matter [4].We also found no changes in grey matter with respect to cortical thickness [5].While it is notable that this investigation was limited to healthy participants and a treatment duration of three weeks, our data still stands in contrast to ketamine data in the rat [1] and suggests that alternative modes of action might be more likely as explanation for the antidepressant effects of SSRIs.Nevertheless, one should consider that this does not categorically rule out a role of these underlying mechanisms in patients with depression.

Source: Neuroscience Applied

DOI: 10.1016/j.nsa.2022.100391