Association Between Toxoplasma gondii Infection and Serum Neurotransmitter Levels in Major Depressive Disorder Patients: A Case-Control Study in Bangladesh

Abstract

Toxoplasma gondii (T. gondii) is an obligate, intracellular, neurotropic protozoan parasite. After primary infection, T. gondii parasite undergoes stage conversion from fast-replicating tachyzoites to slow-replicating dormant bradyzoites, particularly in the brain, and persists for a lifetime of an individual. In this study, the impact of T. gondii infection in individuals with psychological disorder, that is, major depressive disorder (MDD) has been studied. Ninety-five MDD (n = 95) patients were enrolled with age and sex-matched healthy controls (HCs, n = 90). The seroprevalence of T. gondii infection among these individuals was determined using the TOXO IgM/IgG Rapid Test Cassette that determines the anti-T. gondii IgM and IgG antibodies in the serum samples. Furthermore, to understand the impact of T. gondii in developing major depression, the serum level of neurotransmitters (i.e., dopamine, adrenaline, and noradrenaline) was determined using an enzyme-linked immunosorbent assay (ELISA). Our data suggest that anti-T. gondii IgG was slightly higher in MDD patients than in HCs. The level of dopamine was significantly lower in T. gondii-infected MDD patients than in HCs. However, adrenaline and noradrenaline levels showed increasing levels in T. gondii-infected MDD patients. The level of neurotransmitters was correlated with the DSM-D scores of MDD patients. These data, nevertheless, confirm that T. gondii might affect the level of neurotransmitters in MDD patients. However, whether the reduced level of dopamine and increased level of adrenaline and noradrenaline act as contributing factors for the development of MDD is yet to be known.

Keywords: Toxoplasma gondii; adrenaline; dopamine; major depression; noradrenaline.

Figure 1

Proposed model of T. gondii-mediated changes on neurotransmitter level.

Figure 2

The rate of seropositivity of T. gondii in MDD is higher than in healthy controls. The percentage of anti-T. gondii IgG-positive MDD cases and healthy controls were calculated and presented. p value was calculated using chi-square test between healthy controls and MDD cases and considered significant if p < 0.05.

Figure 3

Comparison of seropositivity of T. gondii in MDD patients with age groups and genders. (a) The anti-T. gondii IgG positive and negative cases for age groups 18–30 and 31–60 years were calculated and expressed as the absolute number. (b) In addition, the anti-T. gondii IgG-positive and negative cases were compared for both male and female groups and expressed as the absolute number.

Figure 4

Level of adrenaline, noradrenaline, and dopamine in the serum of MDD patients and healthy controls. The study subjects were divided into three groups: (a) healthy control, n = 24; (b) T. gondii-positive MDD patients, n = 24; (c) T. gondii positive healthy control, n = 8. Concentration (nanograms per milliliter) of adrenaline, noradrenaline, and dopamine was measured through Enzyme-Linked Immunosorbent Assay (ELISA) in the serum of the abovementioned groups. Here, a comparison of the level of (a) adrenalin, (b) noradrenaline, and (c) dopamine was shown between healthy control and T. gondii-positive MDD patients. Besides, the impact of T. gondii was further confirmed by comparing the level of (d) adrenaline, (e) noradrenaline, and (f) dopamine between healthy control and T. gondii-positive healthy control. X-axis represents sample population groups, and Y-axis represents the concentration of respective neurotransmitters in nanograms per milliliter. Data were expressed as mean ± SEM (standard error mean). Significant differences were calculated by unpaired students t-test and considered significant if p < 0.05.

Figure 5

Correlation of the concentration of adrenaline, noradrenaline, and dopamine with DSM-score. In this figure, the concentration of (a) adrenaline, (b) noradrenaline, and (c) dopamine (nanograms per milliliter) was correlated with the respective depressive index calculation (DSM) score. The concentration was calculated as the mean for the healthy control and T. gondii-positive MDD samples and plotted with the DSM score obtained during patients' interviews to diagnose major depression. The X-axis shows sample groups, the left Y-axis represents concentration (nanograms per milliliter), and the right Y-axis represents the DSM score. GraphPad Prism Version 9.0 was used to prepare the figure.