Toxoplasma gondii is a parasite that infects warm-blooded animals. It is interesting to note that the term "toxon" in Greek means "crescent-shaped," which accurately describes one of the parasites three infec-tious stages known as the tachyzoite. Additionally, "plasma" is a Greek word for "creature." Conseque-ntly, the parasites name is derived from its tachyzoite form (Gunn and Pitt, 2012; Bogitsh et al., 2018). Briefly: T. gondiis life cycle is complex and involves both sexual and asexual reproduction. Asexual reproduction occurs in various tissues of mammals and birds, which serve as secondary or intermediate hosts. However, sexual reproduction exclusively takes place in felines digestive epithelium, which serves as the primary or definitive host. Numerous studies have demonstrated that several feline species can function as definitive hosts for T. gondii. This leads to the formation of oocysts excreted in feces (Dubey et al., 2009; Dubey, 2009a; Skariah et al., 2010).  

Furthermore, oocysts become infectious once they sporulate in the environment and can be transmitted through wind and water. Oocysts resist harsh envi-ronmental, physical, and chemical circumstances. This allows them to remain infectious as long as they remain in appropriate environments (Tenter et al., 2000). This parasite belongs to the Apicomplexa phylum, which is commonly referred to as the sporo-zoa. It is a versatile unicellular protist that thrives in a variety of environments. Besides, it is assumed to be an obligate intracellular parasite, which means it can only live within living cells. The apical complex, an evolutionarily distinct organelle beneath the oral cavity, distinguishes this parasite. All apicomplexan parasite groups are pathogenic to humans and animals (Gould et al., 2008; Yoon et al., 2008). T. gondiis life cycle includes three infectious stages: sporulated oocysts with sporozoites, tachyzoites, and tissue cysts containing bradyzoites. All three stages can infect both definitive and intermediate hosts. While, cats become infected by ingesting sporulated oocysts found in the feces of an infected cat through contaminated food or water. They can also become infected by consuming an intermediate host containing bradyzoites. On top of that, vertical transmission from a pregnant mother to her fetus is another significant route of infection (Gunn and Pitt, 2012). T. gondii can infect humans in a variety of ways, the most frequent being the ingestion of oocysts or tissue cysts. Oocysts are common in the environment and may be found in both domestic and stray cats, making them a source of infection. Another way is vertical transmission from mother to fetus. This occurs via the transplacental route (Frenkel et al., 1970; Dubey and Beattie, 1988).

In countries where raw or undercooked meat consump-tion is common, the estimated prevalence of T. gondii is greater than 50%. For instance, in France, where this dietary practice is prevalent, the prevalence rate was 54%. Analogously, tropical regions in Latin America and Africa, characterized by high cat populations and favorable climate conditions for oocyst survival, exhibit a high seroprevalence of the parasite (Jones et al., 2001; Di Carlo et al., 2008; Dubey et al., 2009). Shockingly, an estimated 15% of women of child-bearing age, between 25 and 44 years old, in the United States are infected with T. gondii. Moreover, congenital toxoplasmosis is estimated to occur annually from 400 to 4,000 cases (Jones et al., 2001). On the other hand, T. gondii infects 25% to 30% of the worlds population, although infection rates vary among ethnic groups. In North America, Asia, and Northern Europe, infection rates range from 10% to 30%. Central and Southern Europe report moderate rates of 30% to 50%, while Latin America and the tropical regions of Africa exhibit a high incidence of infection (Robert-Gangneux and Dardé, 2012).

Although T. gondii infection usually remains asymp-tomatic or causes mild flu-like symptoms in healthy individuals, it can have serious consequences for those with compromised immune systems. Toxoplasmosis may cause central nervous system abnormalities, myo-carditis, or pneumonitis in immunocompromised per-sons. Notably, among immunocompromised persons with toxoplasmosis, Toxoplasmic encephalitis is the most prevalent cause of intracerebral mass lesions. This is related to the reactivation of their chronic infection (Schmidt-Hieber et al., 2009; Siberry et al., 2013; Hadiloo, 2023).

Psychopathology definition and statistics

Typically, an individuals psychological state is cate-gorized as balanced or imbalanced based on their level of participation in social activities within society. This is also accompanied by the existence of functional impairments or weaknesses. Psychopathology encom-passes various elements, such as functional limitations, distress, irrationality, and lack of control. It is signi-ficant to note that there may be additional problematic psychological traits that should not be disregarded (Bergner, 1997; Maddux and Winstead, 2015; Cicc-hetti, 2016). Despite the extensive criteria and numerous research papers available, there remains a significant amount of uncertainty and lack of awareness regarding psychopathologys development. These uncertainties result from the complex inter-connections between an individuals genotype and various social environments. In addition, they stem from the fundamental and intense experiences they endured during their early growth stages. However, they also stem from persistent stress and hormonal imbalances they may have faced. Moreover, recent studies have highlighted the potential involvement of diverse parasites and microbes in contributing to these psychological consequences (Giudice and Ellis, 2016; Manning, 2019; Rantala et al., 2019). According to recent statistics, more than 10% of the worlds popu-lation suffers from psychological, mental, and behave-oral disorders. These disorders exert a substantial influence on public health and are associated with numerous factors such as personal distress, disability, and premature mortality. Additionally, these disorders have a substantial economic impact, contributing to 12% of the worldwide disease burden. They also lead to diminished productivity and strain on healthcare resources due to excessive utilization (W.H.O., 2001; Demyttenaere et al., 2004; Wang et al., 2007).

Toxoplasma gondii as a potential cause of behavioral disorders

Previously, it was widely accepted and acknowledged that toxoplasmosis infection in healthy individuals remained dormant and asymptomatic. However, this perspective has evolved over time. Ongoing investi-gations have revealed a connection between latent toxoplasmosis infection and cognitive function changes in both children and older individuals. More-over, numerous studies have associated T. gondii infection with various psychiatric conditions, including schizophrenia, bipolar disorder, and obsessive-com-pulsive disorder. Additionally, this infection has been linked to elevated mortality risk in schizophrenia patients (Dickerson et al., 2007; Campos-Carli et al., 2017). The prevailing consensus among scholars and experts is that behavioral disorders have varied and a variety of causes, including genetic and environmental factors. Nevertheless, it is noteworthy to highlight that numerous theories propose the involvement of infec-tious agents, such as T. gondii, viruses like herpes simplex, CMV, and influenza. This is associated with the occurrence of certain mental and behavioral disorders. T. gondii serves as a significant model for examining the influence of microorganisms on human behavior and mental disorders, as it are frequently related with neuropsychiatric disorders (Fekadu et al., 2010; Flegr, 2013). Schizophrenia factors have been extensively studied and can be categorized into two main groups: genetic and environmental variables. Environmental factors implicate numerous infectious pathogens in schizophrenia development. Particularly, T. gondii has received significant attention and is consistently associated with schizophrenia in various research studies (Sutterland et al., 2015; Owen et al., 2016).

What are the mechanisms and reasons behind Toxoplasma gondii infection leading to behavioral, psychological, and neurological disorders in the host?

Characteristically, when a woman is infected with parasites during pregnancy, it can influence the deve-lopment of specific brain neurons. These neurons include mesolimbic dopaminergic or prefrontal cortical neurons. This impact might involve issues like abnor-mal migration, altered location, or reduced connec-tions, leading to neurodevelopmental problems. Inter-estingly, these initial flaws may not immediately mani-fest as disease symptoms, but instead, they may emerge after a latency period of one to three decades. During childhood, glial progenitor cells continue to undergo proliferation, migration, differentiation, and maturation. In addition, the amount of grey matter in the brain reaches its peak during puberty before gradually declining. Furthermore, significant changes occur in the brains wiring and connections during this period, potentially contributing to symptoms later in life. Understanding these developmental pathways is crucial for identifying early biomarkers and developing effective therapies for neurodegenerative diseases (Paus, 2005; Stiles and Jernigan, 2010). Furthermore, like other pathogens, parasites can modify their own behavior and influence the behavior of their hosts to enhance their survival and reproductive success. Consequently, parasite genes can interact and generate traits that extend beyond the physical boundaries of the parasites own body (Tong et al., 2021). T. gondii, one of the most extensively studied infectious agents, is frequently associated with neuropsychiatric and beha-vioral disorders. However, some explain this phenol-menon through manipulation theories. This theory proposes that parasites, in general, can significantly alter the characteristics of their hosts, a feature that facilitates their transmission to new hosts. In this context, scientists, particularly biologists, psycho-logists, and evolutionary scientists, cite T. gondii as a compelling example. The parasites global existence and remarkable dissemination success, coupled with the severe diseases it causes in humans, contribute to its recognition. Besides, all forms of toxoplasmosis impose substantial economic and social burdens world-wide (Pappas et al., 2009; Torgerson and Macpherson, 2011). 

Nonetheless, it has been suggested that chronic infection with T. gondii leads to numerous alterations in the neurotransmitters involved in the communi-cation between nerve cells within the body. For instance, the parasite controls the secretion rate of specific hormones in the infected individual. The genome of T. gondii contains two regions that closely resemble mammalian genes responsible for encoding the enzyme crucial for dopamine production, called amino acid hydroxylase. This similarity explains the increased availability of dopamine in the hosts brain following chronic localization of T. gondii (Gaskell et al., 2009). T. gondii infection manifests asymptomatic and can lead to mild symptoms. However, it usually begins during childhood and persists in a chronic state, causing the parasite to reside inactively within the organism infected with it. Subsequently, it takes advantage of weakened immunity in certain patients, such as those with AIDS, organ transplant recipients, individuals with various immune disorders, and cancer patients. Exploiting the compromised immune system, the parasite can reactivate the infection, leading to a range of symptoms and potentially fatal outcomes. Reactivation symptoms usually include neurological manifestations like meningitis and encephalitis, as well as cysts and abscesses in the brain. These observations provide additional insights into the potential impact of latent and chronic T. gondii infection on the psycho-logical, behavioral, and neurological conditions of some toxoplasmosis patients (Roberts et al., 2001; Montoya and Liesenfeld, 2004). Due to its direct impact on nerves, T. gondii, the parasite responsible for toxoplasmosis, has been linked to numerous sensory and congenital neurological disorders (Torrey et al., 2007; Torrey and Yolken, 2019). Moreover, numerous research studies have shown that T. gondii possesses an intricate mechanism to penetrate and invade various cells in the brain, particularly those of the central nervous system. Furthermore, the parasite can form cysts within these cells, enabling it to influence the hosts behavior and consequently induce a range of neurological and psychological symptoms in certain patients (Holliman, 1997; Webster et al., 2006; Carruthers and Suzuki, 2007). It is also intriguing to note that both sexually transmitted parasites and the genes of the host share a common interest and object-tive, which is to alter the hosts programming to enhance reproductive viability. Therefore, the hosts survival is crucial to the parasites survival. On the other hand, parasites transmitted through food, such as T. gondii, have different interests and goals. For instance, the parasite aims for the definitive host, such as a feline, to prey upon and consume the intermediate host, such as a mouse. The mouse strives to survive and reproduce to ensure its offsprings continuation. Among the various behaviors associated with toxoplas-mosis, one notable example is the elongation of response times in infected hosts. This arises from the parasites manipulative activities rather than being mere side effects of the infection (Poulin, 1995; Hrdá et al., 2000). To guarantee their survival and propa-gation, certain parasites implement strategies to modify their hosts physical characteristics and behaviors. This manipulation increases the likelihood of transmission from an infected host to an uninfected one. T. gondii can exploit these manipulative activities, both in terms of behavior and morphology, to achieve this goal (Flegr and Hrdy, 1994; Webster, 1994). Numerous mechanisms and pathways have been suggested to explain how the T. gondii parasite influ-ences its hosts behavioral state. One such mechanism involves cytokines, associated with T. gondii infection. These cytokines activate microglia and facilitate neurodegeneration, leading to activation and apoptosis. These proposed mechanisms may contribute to the impact of T. gondii infection on mental disorders in the host, as neurotransmitters and immune dysregulation also play significant roles in the pathophysiology of psychosis and schizophrenia (Flegr, 2013; Fabiani et al., 2013). While postnatal toxoplasmosis contributes to various psychological and neurological impair-ments, it targets specific neurotrophic regions in the brain. These regions include the cerebral hemisphere, cerebellum, basal ganglia, and brain stem. The forma-tion of tissue cysts within neurons and glial cells further explains the emergence of these psychological and behavioral disabilities in individuals who acquire postnatal toxoplasmosis. Congenital toxoplasmosis, on the other hand, presents a range of clinical mani-festations. Some newborns show no symptoms while others experience severe symptoms due to possible neurological abnormalities that may arise years after birth or even during puberty (Avelino et al., 2014; Elzeky et al., 2022). An additional justification for the impact of T. gondii on infected individuals behavior is based on the parasites inclination towards specific regions of the brain. This selective affinity can account for behavioral changes observed in the host, due to localized signal modifications. Furthermore, T. gondii induces specialized enlargement in the brain, eyes, and testes. These are immune-privileged sites that immune cells cannot access. Experimental evidence suggests T. gondii can enter these areas through brain endothelial cells and dendritic immune cells. Consequently, the occurrence of cysts in these regions disrupts their normal functioning, leading to impairments in fear processing and decision-making abilities (Gonzalez et al., 2007; Lachenmaier et al., 2011; Vyas, 2015). Unquestionably, T. gondii is among the most conspi-cuous infectious agents linked to mental and neuro-logical disorders. Given its relationship to a range of psychological, behavioral, and neurological issues in infected patients, this parasite serves as an excellent model for studying the impact of micro-organisms on human behavior and mental disorders (Flegr, 2013).

Behavioral, neurological, and psychopathological disorders associated with Toxoplasma gondii infection

While the host itself influences some behavioral changes following infection, the pathogen causes others to facilitate its own transmission. This provides a plausible explanation for certain parasites ability to interact with their hosts central nervous systems (CNS). Although some infection-related behavioral changes, such as feelings of sadness or overall malaise, may appear broad, they target specific physiological traits of the host to enhance the parasites chances of survival and propagation (Webster et al., 2013). One of the remarkable behavioral changes associated with T. gondii is the phenomenon called "fatal attraction," where infected mice display an unusual attraction to cats scent instead of their natural aversion to it. This alteration in behavior is accompanied by increased activity levels and reduced fear. This is believed to be influenced by the learning and memory impairments caused by the parasite, distinguishing infected mice from their uninfected counterparts (Berdoy et al., 1995; Berdoy et al., 2000; Webster, 2001). It is also intriguing and noteworthy that T. gondii infection is associated with behavioral and cognitive changes in intermediate hosts. For instance, infected chimpanzees are attracted to tiger urine, a member of the feline family. This behavior is interpreted as a developmental adaptation to facilitate the completion of the T. gondii life cycle within the definitive host, which exclusively belongs to the feline family (Webster, 2001; Poirotte et al., 2016; Brüne, 2019). Additionally, the formation of persistent cysts by T. gondii in brain tissue may directly impact specific regions of the brain, such as the amygdala or hippocampus, potentially explaining the occurrence of behavioral and psychological changes observed in individuals infected with T. gondii (Mortensen et al., 2007; Carruthers and Suzuki, 2007; Hari Dass and Vyas, 2014).

Schizophrenia

Toxoplasmosis transitions from a mild and acute infection to a chronic and latent stage. Over the past two decades, numerous studies and research have continuously shown that this latent stage is strongly associated with an increased risk of psychological, neurological, and behavioral disorders in patients. This association has been well-documented, with a notable relationship between toxoplasmosis and schizophrenia patients. Research focusing on these patients has revealed a high prevalence of T. gondii infection, particularly among those experiencing persistent symptoms of schizophrenia and other mental disorders (Torrey et al., 2007; Torrey et al., 2012; Flegr et al., 2014; Sutterland et al., 2015). In addition to what has been mentioned, studies have demonstrated that T. gondii could influence schizophrenia clinical chara-cteristics (Flegr, 2013; Fabiani et al., 2013). Numerous clues have indicated a relationship between toxoplas-mosis and schizophrenia, as changes in brain structure, such as reduced grey matter in the frontal cortex, temporal cortex, cingulate cortex, and thalamus, are commonly observed in individuals with schizophrenia. These same alterations have been found in patients with schizophrenia with toxoplasmosis (Niebuhr et al., 2007; Horacek et al., 2012; McConkey et al., 2013). 

Furthermore, it extends beyond mere alterations in brain morphology. Studies have revealed that schizo-phrenia patients infected with T. gondii exhibit 15 times more positive symptoms than non-infected schizophrenic patients. Moreover, there is a higher likelihood of developing a persistent course of the disease in individuals with both schizophrenia and toxoplasmosis (Wang et al., 2006; Holub et al., 2013; Çelik et al., 2015). Further research and hypotheses have expanded our understanding of this area. It has been proposed that certain characteristics and symptoms observed in schizophrenia patients could be attributed to toxoplasmosis infection. Additionally, schizophrenia and toxoplasmosis may share psycholo-gical symptoms. For instance, both schizophrenia patients and individuals with latent or chronic toxo-plasmosis exhibit increased startle reflex latency. In addition, they show a diminished effect of prepulse on latency in the acoustic startle reflex inhibition test (Horacek et al., 2012; Pearce et al., 2013; Příplatová et al., 2014). The association between schizophrenia and toxoplasmosis extends beyond behavioral and psycho-logical disorders and includes an interconnection with distinctive changes in certain senses, like smell. More-over, toxoplasmosis impact on smell differs based on gender. For instance, research revealed that males perceive diluted cat urine as more pleasant (Flegr et al., 2011). In contrast, infected females find cat urines diluted smell less pleasant (Berdoy et al., 2000). However, several studies have indicated a significant negative impact of schizophrenia on patients performance in odor identification tests, characterize-ation, and smell recognition memory (Flegr et al., 2017).

Self-directed violence, suicide attempts and others

While the majority of studies on T. gondii have mainly concentrated on its associations with schizophrenia, increased rates of toxoplasmosis exposure have been detected in the various other mental diseases, which include psychotic disorder-like symptoms, bipolar disorder, self-directed violence, the suicide attempts, generalized anxiety disorder, the mixed anxiety and depressive disorder, obsessive-compulsive disorder, autism, and pregnancy depression (Xiao et al., 2018). 

Fascinatingly, several animal studies have revealed a strong correlation between toxoplasmosis infection and heightened risk-taking behaviors, including attraction to cat urine, increased adventurousness, exploratory behavior, reduced fear response, and a lack of aversion to open spaces. Surprisingly, toxoplasmosis infection has also been associated with a higher occurrence of motor vehicle accidents, mental and neurological disorders, and substance abuse in humans. Addi-tionally, suicide attempts have increased (Johnson et al., 2018).

Parkinsons disease

Furthermore, several findings regarding T. gondii infection have established its association with various neurological disorders in humans, including Parkin-sons disease. Parkinsons disease is a neurological condition characterized by the degeneration of specific neurons in the substantia nigra. This is a region in the brain stem responsible for dopamine production. Dopamine serves as a crucial neurotransmitter invol-ved in coordinating normal movement (Golbe et al., 2010; Miman et al., 2010). It is worth mentioning that, in a study conducted by Miman et al. (2010), the potential association between Toxoplasma gondii infection and Parkinsons disease was investigated. The researchers analyzed data from a large study involving individuals in Turkey. They observed a higher like-lihood of Parkinsons disease development in those infected with Toxoplasma gondii. The authors pro-posed that this connection could be attributed to the parasites ability to damage brain neurons. However, further research is required to validate this correlation and gain a deeper understanding of the underlying mechanism through which Toxoplasma gondii might contribute to Parkinsons disease (Miman et al., 2010).

Gender-related alterations associated with Toxo-plasma gondii infection.

Even though the vast majority of infected individuals show no apparent health consequences from T. gondii infection, latent and chronic forms of the disease can lead to involuntary changes in behavior and per-sonality. Interestingly, these behavioral alterations can vary depending on the infected persons sexuality. For instance, infected men may display higher levels of suspicion, jealousy, and dogmatism. On the other hand, infected women may exhibit increased moral values, conscientiousness, and persistence compared to others. These findings suggest a potential gender-specific impact of infection on the personality traits. However, further research is required to fully under-stand the extent and causality of these associations (Flegr, 2007; Del Giudice, 2019).

Impulsivity and aggression 

Additionally, toxoplasmosis impacts the corticolimbic region, which regulates impulsivity and aggression in humans. Furthermore, recent studies have broadened the investigation into psychological and mental dis-orders, including schizophrenia, obsessive-compulsive disorder, and suicidal tendencies in individuals with latent and chronic toxoplasmosis. These findings suggest a potential connection between toxoplasmosis and various psychological conditions (Torrey and Yolken, 2019; Inceboz and Inceboz, 2021). Never-theless, studies investigating the behavioral biology of the parasite T. gondii have revealed the fascinating neuroendocrinological discoveries, particularly in terms of the regulation & interaction between the brain and hormones (Tong et al., 2021). 

Furthermore, pursuant to a study conducted by Cook and colleagues, there was a correlation between T. gondii IgG seropositivity and increased impulsive sensation-seeking, specifically related to suicidal self-directed violence (SSDV) disinhibition, in young men aged 20 - 59 years (with a median age of 60). The study also observed that aggression and impulsivity, which are considered endophenotypes for SSDV, were associated with latent T. gondii infection in a manner specific to gender and age. This study suggests that T. gondii infection may influence behavior & mental health, particularly in terms of impulsivity & aggres-sion (Cook et al., 2015).

Cancers 

Toxoplasmosis has been detected in various cancer types, including lymphoma, acute and chronic leuke-mia, and myeloma. Furthermore, recent research has identified the presence of anti- T. gondii antibodies in women with breast and ovarian cancers. However, the specific mechanism behind this association remains unknown, but it is evident that toxoplasmosis contri-butes to tumor advancement (Aabasian et al., 2016). Yuan and colleagues conducted a study to examine the potential association between Toxoplasma infection and cancer by detecting anti- T. gondii antibodies in cancer patients. The study involved 267 cancer patients who underwent ELISA testing. It revealed higher rates of T. gondii IgG positivity than the control group. Specifically, the nasopharyngeal carcinoma and rectal cancer groups exhibited significantly higher rates of T. gondii IgG seropositivity than other cancer groups. However, IgM seropositivity rates fluctuated not significantly. These findings suggest a link between T. gondii infection and various cancers, including naso-pharyngeal carcinoma and rectal cancer. Nevertheless, further research is required to determine whether T. gondii infection is a causal factor for cancer and whether it can be targeted for cancer prevention. This study underscores the importance of investigating infectious agents involvement in cancer development and progression (Yuan et al., 2017).

Psychological disorders in individuals co-infected with Toxoplasmosis and HIV/AIDS.

Toxoplasma gondii-related psychological disorders are prevalent in AIDS patients with compromised immune systems, where latent infection is reactivated. Pursuant to research on AIDS cases with toxoplasmosis, up to 60% of patients have abnormal mental states that appear as delusions, auditory hallucinations, and cognitive deficits (Israelski and Remington, 1988).

Bipolar disorder

Bipolar disorder (BD) is a chronic and recurring mental disorder that contributes to disability and mor-tality on a global scale. BD origins are complex, involving a combination of genetic inheritance and environmental risk factors. Among the various factors implicated, infectious agents have been enumerated. There is growing evidence pointing to the significance of immunological dysfunction in the development of the disorder. Moreover, inflammation and oxidative stress have been suggested as potential contributors to the onset and progression of BD, highlighting the importance of a systematic treatment approach that addresses both the biological and psychological aspects of the disorder (Del Grande et al., 2017). Highlighting the potential indirect contribution of T. gondii to bipolar disorder, also known as manic depression, is important. Numerous infectious agents, including T. gondii, have been linked to psychosis, either through direct effects on brain cells or indirect influences on immune cells and neurotoxic compounds (Inceboz and Inceboz, 2021). Numerous investigations have been conducted to investigate the relationship between bipolar disorder (BD) and toxoplasmosis infection. One such study involved 110 BD patients and 106 healthy individuals residing in France, a country with a high toxoplasmosis seroprevalence rate. The study found significantly higher seropositivity and antibody levels to T. gondii in BD patients compared to the control group. These results indicate that toxoplasmosis infection could potentially play a role in the development of BD (Hamdani et al., 2013).

Heightened libido

Toxoplasmosis is commonly known as a food-borne disease; however, it can also be transmitted sexually in rats. Infected rat males can carry T. gondii in their sperm, allowing the parasite to reach the female during mating. Interestingly, T. gondii -infected male rats become more attractive to females, while uninfected females tend to spend more time near infected males, providing them with increased reproductive oppor-tunities. These findings indicate that the parasite mani-pulates the hosts behavior to enhance its own sexual transmission routes. This demonstrates parasites ability to influence their hosts behavior for their own benefit. Such observations highlight the complex and intricate interactions between parasites and their hosts (Vyas, 2013; Vyas, 2015).

Autism 

Autism, a neurodevelopmental disorder with diverse characteristics, affects approximately one in sixty-eight children and is typically diagnosed in their second year of life (Nayeri et al., 2020). Numerous research studies have established a relationship between a positive maternal toxoplasmosis test and elevated autism risk. One hypothesis proposes that T. gondii tachyzoites may infiltrate specific types of brain cells in the cerebellum, influencing signaling pathways and trans-mission systems. The parasite participates in numerous tasks and functions, including cell apoptosis, immune cell maturation, and antimicrobial activities. Further-more, studies have linked the parasite to the activation of apoptosis in neural stem cells through the stress pathway in the endoplasmic reticulum (Fond et al., 2013; Wang et al., 2014; Al Malki et al., 2021).

Alzheimers disease and insomnia

Nayeri et al. have determined that toxoplasmosis poses a risk factor for Alzheimers disease. The findings of several studies linking toxoplasmosis infection and Alzheimers disease reinforce this conclusion, high-lighting the requirement for special attention from healthcare professionals and patients (Nayeri et al., 2021). Furthermore, aside from the aforementioned association between T. gondii infection & Alzheimers disease, another study revealed a relation-ship between toxoplasmosis prevalence and insomnia. Particularly, men over fifty with toxoplasmosis have shown a higher susceptibility to insomnia than others (Alva-rado-Esquivel et al., 2022).

Hormonal and neurotransmitter changes that can occur in people infected with Toxoplasma gondii.

Toxoplasma gondii infection promotes hormone and neurotransmitter changes. Patients infected with T. gondii have shown alterations in the levels and fun-ctioning of several hormones and neurotransmitters. For instance, the infection is related to fluctuations in dopamine, a neurotransmitter involved in motivation and reward. This results in elevated dopamine levels in certain areas of the brain. Likewise, T. gondii infection has been attributed to changes in serotonin, a neuro-transmitter critical for mood control. The infection may also affect hormone levels such as cortisol, which regulates the stress response, and testosterone, which participates in reproductive and sexual processes. These findings illustrate the complicated link between T. gondii and the neuroendocrine system, revealing the parasites potential influence across numerous physiological systems (Flegr et al., 2014; Prandovszky et al., 2020). Latent toxoplasmosis extends beyond psychological, behavioral, and neurological changes. Several studies have established a relationship between latent toxoplasmosis and alterations in specific hor-mones and neurotransmitters in infected animals and humans. This influence is particularly notable on certain sex and steroid hormones (Henry and Beverley, 1976; Kittas and Henry, 1979). The part of the article that follows delves into some of the significant hormones and neurotransmitters influenced by toxo-plasmosis infection.

Dopamine

Furthermore, T. gondiis contribution to the onset of psychological disorders in toxoplasmosis patients can be related to the brains immunological response to the parasite as well as its biochemical activity (Silva et al., 2002; Hunt et al., 2017). In response to T. gondii infection, the body produces gamma interferon, which helps to maintain latent and chronic infection by stimulating astrocytes in the brain to produce indol-eamine 2,3 dioxygenase (IDO), an enzyme involved in the degradation process via the Kynurenine metabolic pathway (Silva et al., 2002; Hunt et al., 2017). 

Consequently, due to the synthesis of indoleamine 2, 3 dioxygenase (IDO), there is a decrease in the level of tryptophan, an essential amino acid for T. gondii replication. This mechanism leads to the production of specific compounds with neurotoxic properties (Elsheikha et al., 2016) and directly impacts the balance of neurotransmitters through the involve-ment of two genes. In a similar manner to the human gene, T. gondii directly enhances dopamine activity, which plays a crucial role in the development of schizo-phrenia, autism, and various other mental disorders (Torrey et al., 2012; Krause and Müller, 2012; Sutterland et al., 2015; Qayyum et al., 2015). T. gondii may also affect the levels of the neurotransmitter in the intermediate hosts brains and play a significant role in increasing the levels of dopamine secretion among neurons (Prandovszky et al., 2011), possibly by influencing the ways of self-expression of the encoding genes for an enzyme that determines the rate of dopamine synthesis (Gaskell et al., 2009). T. gondii also encodes two essential enzymes for the production of dopamine, a neurotransmitter whose concentration increases in the human brain of toxoplasmosis patients and plays a significant and crucial role in side effects (hallucinations and delusions) in schizophrenia patients (Willner, 1997; Flegr et al., 2003; Gaskell et al., 2009). Furthermore, elevated, or modified levels of dopamine have been observed in rodents and humans infected with T. gondii, as well as in individuals with schizophrenia and other affective disorders such as obsessive-compulsive disorder (OCD), bipolar dis-order, and those with a history of suicide attempts. Additionally, recent research indicates that the parasite itself may be a potential source of this dopamine (Webster et al., 2013). Studies on rats have revealed that the parasite has the potential to alter dopamine levels in the host, influencing glutamatergic brain circuits. Interestingly, these pathways closely match the recognized neurotransmitter patterns identified in people with schizophrenia, despite the fact that current treatment techniques for schizophrenia target antipsychotic medicines anti-dopaminergic activity. Surprisingly, several antipsychotics have anti-parasitic characteristics (Brüne, 2020).

Sex hormones 

An investigation suggested that the infection caused by T. gondii is influenced by sex hormones, which can impact the immune system and consequently affect susceptibility to diseases in general. This is particularly pertinent because T. gondii can lead to congenital disease if contracted during pregnancy (Roberts et al., 2001). In addition to its association with psychiatric and behavioral disorders, toxoplasmosis has been linked to increased sex hormone secretion, particularly testosterone. Various studies have demonstrated that T. gondii enhances hormone production (Del Giudice, 2019; Tong et al., 2019). Testosterone, known as the male sexual hormone, reduces anxiety and fear. It is believed to play a crucial role in T. gondiis effects during its interaction with the brain. Furthermore, T. gondii infection also stimulates arginine vasopressin synthesis in a specific brain region called the medial amygdala. This area contains nerve cells involved in the perception of sexual hormones and is connected to brain regions responsible for arousal and stimulation (Hari Dass and Vyas, 2014; Tong et al., 2019; Tong et al., 2021b). In the male reproductive system, the testes serve as a barrier that restricts immune cells and pathogens access. Nonetheless, pathogens, including T. gondii, surpass this barrier and invade rats testes. This has been confirmed by the detection of T. gondii and other species in rat ejaculates. As a result, T. gondii infection enhances the production of testo-sterone, and this hormone, in turn, interacts with the hosts brain, further facilitating the effects of the parasite (Tong et al., 2021). Furthermore, according to Oktenli et al. (2004), acute T. gondii infection can lead to temporary gonadal insufficiency unrelated to disease progression. Interestingly, T. gondii infection has been observed to increase testosterone levels in infected animals and promote the expression of luteinizing hormone receptor mRNA (LHR). On the other hand, women with hyperprolactinemia, a condition charac-terized by high levels of prolactin hormone, had a lower prevalence of toxoplasmosis than other women (Oktenli et al., 2004; Galvan-Ramirez et al., 2014). In more detailed terms, T. gondii infection leads to an elevation in the number of luteinizing hormone (LH) receptors and specific enzymes involved in testo-sterone conversion from its precursor within Leydig cells. T. gondii influences testosterone levels by this mechanism, subsequently; the increased testosterone circulates in the bloodstream and crosses the blood-brain barrier, resulting in an upregulation of arginine vasopressin (AVP) transcription in the medial amyg-dala. While these neurons are part of the extra-hypothalamic vasopressin system and influence male rodent sociosexual behavior. It is proposed that elevated levels of vasopressin in the central amygdala system reduce fear by enhancing approach behavior (Singh et al., 2020). Furthermore, numerous studies have validated a notable rise in the levels of hormones 17β-estradiol and progesterone during the second and third trimesters of pregnancy, coinciding with an increased incidence of the toxoplasmosis infection (Montoya and Remington, 2008; Al-warid and Al-qadhi, 2012). Across the menstrual cycle, there are fluctuations in the levels of these hormones (E2 and Progesterone), which significantly influence immune system cells. This hormonal effect on the immune system could potentially lead to increased suscep-tibility to toxoplasmosis infection (Roberts et al., 2001). Due to the potential occurrence of progesterone secretion abnormalities during pregnancy, proges-terone levels become irregular in the women with toxoplasmosis during that period. Additionally, research has shown that toxoplasmosis-infected sheep experience low progesterone levels throughout pregnancy (Galvan-Ramirez et al., 2014). In response to the potential occurrence of progesterone secretion abnormalities during pregnancy, progesterone levels become irregular in women with toxoplasmosis during that period. Additionally, research has shown that toxoplasmosis-infected sheep experience low proges-terone levels throughout pregnancy (Galvan-Ramirez et al., 2014). Moreover, studies conducted on mice have highlighted the significance of sexual hormones, revealing that administering estrogen exacerbated the disease in mice, whereas a gonadectomy improved disease resistance. Similarly, in guinea pigs infected with T. gondii and subsequently treated with estrogen, there was an increase in mortality and a deterioration of infection due to a significant decline in cellular immunity caused by high doses of estrogen as compared to untreated control animals (Kittas and Henry, 1979).

Cortisol

A study conducted to assess the impact of T. gondii infection on testosterone and cortisol levels as well as psychological stress in patients with T. gondii found a notable statistical association. The study revealed that toxoplasmosis patients exhibited elevated levels of testosterone and cortisol in their blood plasma. In addition, they showed elevated levels of stress and anxiety. However, it was observed that only males with toxoplasmosis experienced an increase in depression, as indicated by the study conducted by (Shirbazou et al., 2011). One hypothesis or explanation put forward to understand the high levels of steroid hormones in patients with toxoplasmosis suggests that a combination of weakened cellular immunity and increased steroid hormone levels plays a significant role in enabling the parasite to persist in the infected persons body. The rise in steroid hormones, coupled with a compromised immune system, aids parasite survival in the infected individual. Survival is the primary objective of the parasite, as highlighted in Flegr et al research. In 1996 several studies have revealed that latent toxoplasmosis leads to a reduction in corticosterone hormone secretion due to the withdrawal of dendrites from the basolateral amygdala. This reduction significantly contributes to various behavioral abnormalities, as demonstrated in (Mitra et al., 2013).

Thyroid hormones

Since T. gondii can infect numerous organs within the human body, such as the brain, eyes, muscles, and various visceral organs, its impact is particularly significant when it infiltrates the brain. In such cases, it can stimulate the hypothalamus nerves, leading to disruption of TSH secretion and abnormal secretion of T3 and T4 hormones. Furthermore, it can cause the thyroid gland to undergo changes, as well as notably elevate thyroid peroxidase levels. This is highlighted by research conducted by (Al-Issawi and Aysir, 2020). A study conducted in the Kurdistan Region of Iraq aimed to explore the link between latent toxoplasmosis and thyroid hormone levels in schizophrenia patients. The investigation indicated that schizophrenia patients had a higher likelihood of contracting toxoplasmosis. Moreover, T. gondii infection resulted in elevated levels of serum T3 and T4 hormones in patients with schizophrenia. Consequently, the study suggests that treatment and screening programs for toxoplasmosis should be prioritized among schizophrenia patients (Mohammed and Mageed, 2022). T. gondii-infected Nylar female mice eventually developed hypogon-adotropic hypogonadism due to the hypothalamic dysfunction. In these animals, T. gondii infection lowers serum thyroxine (T4) levels. Infertility can result from the hypogonadotropic hypogonadism, a reproductive system condition. Serum thyroxine insufficiency may play a role in metabolic problems in these animals (Galvan-Ramirez et al., 2014).

The present study revealed findings that challenge the prevailing consensus regarding toxoplasmosis. It reveals its typical asymptomatic nature or mani-festation of flu-like symptoms, and its ability to remain dormant throughout a patients life. Recent research suggests that it poses a significant risk, particularly to those with compromised immune systems, as it can reactivate later. Moreover, this parasitic infection influences psychological and neurological behavior by impacting the production of specific hormones and neurotransmitters. Notably, the T. gondii infection is associated with increased susceptibility to mental health disorders such as schizophrenia, autism, Alzheimers, and bipolar disorder. In addition, it has been associated with behavioral changes like impul-sivity and aggression. It is therefore crucial to fully understand the potential ramifications of this parasite on both physical and mental well-being. Moreover, infection with this parasite can alter the secretion rates of various hormones and neurotransmitters, including the dopamine, thyroid hormones, cortisol, and sex hormones.

All authors contributed evenly to this study. The researchers have emphasized that they have no source of funding.

The authors state that they have no conflicts of interest regarding the publication of this study