Making Sense of Life‐History Effects of the Antidepressant Citalopram in the Copepod Nitocra spinipes Using a Bioenergetics Model

Abstract

The global consumption of human antidepressants has steadily increased over the last years. The most widely prescribed antidepressants are the selective serotonin reuptake inhibitors (SSRIs), which have been linked to various lifehistory effects in nontarget organisms. We investigated the effects of the SSRI citalopram hydrobromide on the life history of the copepod Nitocra spinipes. Slight but significant developmental delay effects were observed at nominal concentrations of 0.1 and 1 µg/L, with stronger effects occurring at measured concentrations of 178 µg/L and above. At 77 µg/L and above, a significant increase in adult body length and offspring production/brood was found, although the time between brood releases remained unaffected. The pre-adult surviving fraction was significantly reduced (by 44%) at 765 µg/L. For a mechanistic evaluation of these observations, we used a bioenergetics model for N. spinipes based on the dynamic energy budget theory. Toxicokinetic and toxicodynamic submodels were used to dynamically simulate the chemical uptake and elimination, as well as dose-response relationships for hypothetical physiological modes of action and survival over time. Although none of the commonly invoked physiological modes of action, acting on assimilation, maintenance, growth, or offspring production, could explain the observed combination of effects, a newly proposed physiological mode of action acting on the process of maturation delivered correct predictions in terms of each effect's direction. The model fits could be further improved by allowing for a gentler concentration-effect slope and by adding an auxiliary physiological mode of action acting on the reproduction efficiency. The quantitative explanations provided in the present study offer a starting point for exploratory simulation studies investigating the effects of SSRIs at higher ecological levels.

Investigating Population‐Level Toxicity of the Antidepressant Citalopram in Harpacticoid Copepods Using In Vivo Methods and Bioenergetics‐Based Population Modeling

“… c Maturation efficiency was used by Koch and De Schamphelaere (2021) to model stress effects on the maturation process.…”

“…Dynamic effects on physiological processes caused by the test chemical are modeled via direct effects on specific DEB parameters. In the case of the antidepressant drug citalopram hydrobromide, effects on the maturation efficiency κ H (prepuberty) and the reproduction efficiency κ R (postpuberty) are modeled according to the findings of Koch and De Schamphelaere (2021):…”

“…The purpose of the present study was to investigate whether the effects observed by Koch and De Schamphelaere (2021) could be realistically extrapolated from the individual to the population level using a relatively simple individual‐based model (IBM). In contrast to more traditional population models such as matrix models, which usually regard a population as a structured group of multiple, each in itself homogeneous age classes, IBMs—as their name indicates—simulate each individual of a population separately.…”

“…In a recent study investigating the effects of the selective serotonin reuptake inhibitor (SSRI) citalopram hydrobromide on the life history of the harpacticoid copepod Nitocra spinipes , various lethal and sublethal effects were observed at concentrations of 77 µg L −1 and above. These included significant effects on (a) the preadult survival of the copepods at 765 µg L −1 , (b) the development time from hatching until reaching the adult stage at 178 µg L −1 , (c) the body length of adult females at 77 µg L −1 , and (d) the offspring produced during a single brood of a female at 77 µg L −1 (Koch & De Schamphelaere, 2021). Using the dynamic energy budget (DEB) theory (Kooijman, 2009) as the foundation for a bioenergetics‐based model of the copepod's life history, the authors argued that the observed sublethal effects could be explained best by an increase of the energetic costs for maturation before reaching the adult stage and an increase of the reproduction efficiency after reaching the adult stage.…”

“…b Reproduction efficiency refitted to control data byKoch and De Schamphelaere (2021). c Maturation efficiency was used byKoch and De Schamphelaere (2021) to model stress effects on the maturation process. d Metamorphosis is morphological only and has no implications for DEB rules.…”