Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

Abstract

It has been shown that the functional architecture of the default mode network (DMN) can be affected by serotonergic challenges and these effects may provide insights on the neurobiological bases of depressive symptomatology. To deepen our understanding of this possible interplay, we used a double‐blind, randomized, cross‐over design, with a control condition and two interventions to decrease (tryptophan depletion) and increase (tryptophan loading) brain serotonin synthesis. Resting‐state fMRI from 85 healthy subjects was acquired for all conditions 3 hr after the ingestion of an amino acid mixture containing different amounts of tryptophan, the dietary precursor of serotonin. The DMN was derived for each participant and session. Permutation testing was performed to detect connectivity changes within the DMN as well as between the DMN and other brain regions elicited by the interventions. We found that tryptophan loading increased tryptophan plasma levels and decreased DMN connectivity with visual cortices and several brain regions involved in emotion and affect regulation (i.e., putamen, subcallosal cortex, thalamus, and frontal cortex). Tryptophan depletion significantly reduced tryptophan levels but did not affect brain connectivity. Subjective ratings of mood, anxiety, sleepiness, and impulsive choice were not strongly affected by any intervention. Our data indicate that connectivity between the DMN and emotion‐related brain regions might be modulated by changes in the serotonergic system. These results suggest that functional changes in the brain associated with different brain serotonin levels may be relevant to understand the neural bases of depressive symptoms.

MDMA-induced changes in within-network connectivity contradict the specificity of these alterations for the effects of serotonergic hallucinogens

“…Qualitative comparison with other monoaminergic drugs Our literature search yielded nine fMRI studies which investigated effects of levodopa [44,45], haloperidol [45], escitalopram [46], methylphenidate [47], d-amphetamine [48], bupropion [49], tryptophan depletion/loading [50], and citalopram [51]. One study reported decreased FC within ten of ten investigated networks after citalopram, but it was not reported whether these findings were significant [52].…”

“…Impacts on neurotransmitter systems are shown using the same color scheme. This table refers to results in[4][5][6][44][45][46][47][48][49][50][51][52] and findings in this study.…”

No evidence for the involvement of serotonin or the 5-HTTLPR genotype in intertemporal choice in a larger community sample

“…Procedure. The experiment and results described in this manuscript are part of a larger project that investigates the influence of 5-HT on several decision-making parameters and fMRI measures (Deza-Araujo et al, 2018;Neukam et al, 2018). For this study, we aimed for 100 homozygous subjects.…”

Multi Platforms Strategies and Metabolomics Approaches for the Investigation of Comprehensive Metabolite Profile in Dogs with Babesia canis Infection

“…Although serotonin is best known for its role as a neurotransmitter, it plays an important role in mood, appetite, metabolism, vasoconstriction, and platelet function [81][82][83][84]. In our research, the level of serotonin was decreased.…”