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PURPOSE: This article provides an overview of the evidence of a potential pathophysiological relationship between depression, suicide, and the Toxoplasma gondii (T. gondii) infection. It discusses the role of inflammatory processes in depressive illness and the infection theory of psychiatric disease. It also provides guidelines for the screening, diagnosis, and treatment of depression for nurse practitioners (NPs). DATA SOURCE: A narrative review was conducted of the literature from PubMed, PsycINFO, and Google Scholar. References of identified articles were also reviewed. CONCLUSIONS: Seropositivity of the obligate intracellular protozoan parasite, T. gondii is related to various mental health disorders including schizophrenia, suicide attempt, depression, and other neuropsychiatric diseases. Depressive symptoms have been linked to interferon-gamma (IFN-gamma) blocking T. gondii growth by inducing indoleamine-2,3-dioxygenase (IDO) activation and tryptophan depletion, which results in a decrease of serotonin production in the brain. Although exposure to T. gondii was considered unlikely to reactivate in immune-competent individuals, new findings report that this reactivation may be triggered by immune imbalance. IMPLICATIONS FOR PRACTICE: NPs caring for patients with psychiatric illness need to understand the potential mechanisms associated with depression and the T. gondii infection in order to provide effective screening, treatment, and disease prevention.