Understanding target-specific effects of antidepressant drug pollution on molluscs: A systematic review protocol
Maurice E. Imiuwa, Alice Baynes,Edwin J. Routledge
Abstract
The environmental prevalence of widely prescribed human pharmaceuticals that target key evolutionary conserved biomolecules present across phyla is concerning. Antidepressants, one of the most widely consumed pharmaceuticals globally, have been developed to target biomolecules modulating monoaminergic neurotransmission, thus interfering with the endogenous regulation of multiple key neurophysiological processes. Furthermore, rising prescription and consumption rates of antidepressants caused by the burgeoning incidence of depression is consistent with increasing reports of antidepressant detection in aquatic environments worldwide. Consequently, there are growing concerns that long-term exposure to environmental levels of antidepressants may cause adverse drug target-specific effects on non-target aquatic organisms. While these concerns have resulted in a considerable body of research addressing a range of toxicological endpoints, drug target-specific effects of environmental levels of different classes of antidepressants in non-target aquatic organisms remain to be understood.
Introduction
The widespread occurrence of human pharmaceuticals in the environment is a cause of increasing concern. Particularly worrisome is the presence, in the aquatic environment, of neuromodulatory pharmaceuticals developed to specifically target critical-function biomolecules such as monoamine neurotransmitter re-uptake transporters, their synaptic receptors and deamination enzymes in humans, that are well conserved across animal phyla [1–5]. Monoamine neurotransmitters are biogenic amines containing one amine group (and essentially include serotonin, norepinephrine and dopamine), that are critical in the modulation of virtually all brain functions, and play key roles in the regulation of physiological processes such as development, reproduction, autonomic functions, hormone secretion and complex behaviours [6–9]. The synaptic activity of monoamines is tightly modulated by their re-uptake transporters, pre-and post-synaptic receptors and deaminating oxidases [6,10,11]. These critical-function biomolecules regulate the intensity and duration of synaptic monoamine signaling, and for this reason, they are key pharmacological targets for antidepressant drugs [6,12]. Antidepressants are a major class of psychotropic drugs that target and inhibit monoamine re-uptake transporters, their synaptic receptors and terminating enzymes, thereby interfering with the endogenous modulation of monoaminergic neurotransmission, a key neurophysiological process [13].
Material and methods
The systematic review will be conducted in line with the guidelines by the Collaboration for Environmental Evidence (CEE) [81]. Accordingly, the systematic review protocol was developed following the CEE Reporting standards for Systematic Evidence Synthesis (ROSES) [82] (See S1 Table for ROSES; S2 Table for PRISMA-P in compliance with PLOS One protocol publication criteria). As recommended by Whaley et al. [83], the protocol has been registered in the Open Science Framework (OSF) registry, with the Registration DOI: 10.17605/OSF.IO/P4H8W.
Discussion
Given the wide variety of aquatic molluscan species, classes of antidepressant drugs and exposure conditions reported in laboratory studies, the data are not considered to be amenable to meta-analysis [105], and only narrative synthesis will be conducted. Accordingly, data on all study characteristics and statistically significant results of each included study will be presented with tables [105]. Further, data within distinct subgroups comprising species of molluscs, class of antidepressants, exposure concentrations and nature of effects will be summarized, compared and contrasted [106]. The synthesis will be followed by an extensive discussion. Where full text-screened articles are excluded from data synthesis, a list of affected studies with the reason for exclusion will be provided. The EPPI-Centre approach to assessing the overall robustness of the synthesis will be adopted, and described in terms of the internal validity of included studies [107].
Acknowledgments
The authors would like to thank Joanne Mcphie, an academic liaison librarian, Brunel University London, for technical assistance with the search strategy development.
Citation: Imiuwa ME, Baynes A, Routledge EJ (2023) Understanding target-specific effects of antidepressant drug pollution on molluscs: A systematic review protocol. PLoS ONE 18(6): e0287582. https://doi.org/10.1371/journal.pone.0287582
Editor: Peter P. Fong, Gettysburg College, UNITED STATES
Received: March 26, 2023; Accepted: June 6, 2023; Published: June 27, 2023
Copyright: © 2023 Imiuwa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data from this study will be made available upon study completion.
Funding: MEI received funding from Tertiary Education Trust Fund (TETFund), Nigeria (https://tetfund.gov.ng/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
