Latent toxoplasmosis and psychiatric symptoms – A role of tryptophan metabolism? (original) (raw)
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Behavioural Brain Research, 2019
Toxoplasma gondii (TOX) is an intracellular parasite which infects warm-blooded animals including humans. An increasing number of clinical studies now hypothesize that latent toxoplasmosis may be a risk factor for the development of psychiatric disease. For depression, the results have been varied and we speculate that genetic background is important for the response to latent toxoplasmosis. The main objective of this study was to elucidate geneenvironment interactions in the behavioural response to TOX infection by use of genetically vulnerable animals (Flinders sensitive line, FSL) compared to control animals (Flinders resistant line, FRL). Our results show that all infected animals displayed increased anxiety-like behaviour whereas only genetically vulnerable animals (FSL rats) showed depressive-like behaviour as a consequence of the TOX infection. Furthermore, peripheral cytokine expression was increased following the infection, primarily independent of strain. In the given study 14 cytokines, chemokines, metabolic hormones, and growth factors were quantified with the bead-based Luminex200 system, however, only IL-1α expression was affected differently in FSL animals compared to FRL rats. These results suggest that latent TOX infection can induce anxiety-like behaviour independent of genetic background. Intriguingly, we also report that for depressive-like behaviour only the vulnerable rat strain is affected. This could explain the discrepancy in the literature as to whether TOX infection is a risk factor for depressive symptomatology. We propose that the low grade inflammation caused by the chronic infection is related to the development of behavioural symptoms.
No association between current depression and latent toxoplasmosis in adults
Changes in behaviour and cognition have been associated with latent infection from the apicomplexan protozoan Toxoplas-ma gondii (Nicolle et Manceaux, 1908) in both animal and human studies. Further, neuropsychiatric disorders such as schizophrenia have also been associated with latent toxoplasmosis. Previously, we found no association between T. gondii immunoglobulin G anti-body (IgG) seropositivity and depression in human adults between the ages of 20 and 39 years (n = 1 846) in a sample representative of the United States collected by the Centers for Disease Control as part of a National Health and Nutrition Examination Survey (NHANES) from three datasets collected between 1999–2004. In the present study, we used NHANES data collected between 2009 and 2012 that included subjects aged 20 to 80 years (n = 5 487) and used the Patient Health Questionnaire 9 (PHQ-9) to assess depression with the overall aim of testing the stability of the results of the prior study. In the current study, the seroprevalence of T. gondii was 13%. The percentage of subjects reporting clinical levels of depression assessed with the PHQ-9 was 8%. As before, we found no association between T. gondii IgG seroprevalence and depression (OR = 1.01, 95% CI = 0.81–1.25; p = 0.944) while controlling for sex, educational attainment, race-ethnicity, age, poverty-to-income ratio and cigarette smoking. We also found no positive associations between anti-T. gondii antibody titre and depression (OR = 1.00, 95% CI = 0.96–1.06; p = 0.868). Moreover, we found no association between T. gondii seroprevalence or antibody titre and suicidal ideation (seroprevalence: OR = 1.22, 95% CI = .85–1.75; p = 0.277, titre: OR = 1.05, 95% CI = 0.98–1.14; p = 0.177). Defining depression to also include subjects currently taking antidepressant medication even with non-elevated questionnaires did not find evidence of a positive association between latent toxoplasmosis and depression. In the present study, neither T. gondii seroprevalence nor anti-T. gondii antibody titre was positively associated with depression or suicidal ideation among subjects aged 20 to 80 years.
Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1 846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control’s National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T. gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186–1.258), GAD (OR = 0.737, 95% CI = 0.218–2.490) or PD (OR = 0.683, 95% CI = 0.206–2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.
Biological Psychiatry, 2012
Background-Toxoplasma gondii (T. gondii) is a neurotropic protozoan parasite that causes persistent infection in humans. A substantial literature suggests that schizophrenia is associated with increased seroprevalence of T. gondii, but a possible link of the parasite with mood disorders has not been as thoroughly investigated. Methods-We examined the association of Toxoplasma-specific IgG results with mood disorder outcomes in 7440 respondents from the third National Health and Nutrition Survey (NHANES III), which is a nationally representative sample of the U.S. noninstitutionalized civilian population. Regression models were adjusted for numerous potential confounders including tobacco smoking and C-reactive protein levels. Results-No statistically significant associations were found between T. gondii seroprevalence and a history of major depression (n=574; adjusted odds ratio, 0.8; 95% CI 0.5-1.2), severe major depression (n=515; adjusted odds ratio, 0.8; 95% CI, 0.6-1.2), dysthymia (n=548; adjusted odds ratio, 1.1; 95% CI 0.7-1.8), or dysthymia with co-morbid major depression (n=242, adjusted odds ratio, 1.2; 95% CI 0.6-2.4), all p-values were >0.05, including analysis stratified by gender. However, there was a significant relationship between T. gondii seroprevalence and bipolar disorder type I for respondents in which both manic and major depression symptoms were reported (n=41; adjusted odds ratio, 2.4; 95% CI, 1.2-4.8; p<0.05). Conclusions-In a population-based sample, T. gondii seroprevalence is not elevated in unipolar mood disorders but is higher in a subset of respondents with a history of bipolar disorder type 1.
Tryptophan hydroxylase gene (TPH1) and peripheral tryptophan levels in depression
Journal of Affective Disorders, 2008
Background: Genetic variants have been discovered in two genes encoding for tryptophan hydroxylase (TPH)-TPH1 and TPH2. Low tryptophan (TRP) levels are associated with depression and may arise because of stress. Evidence suggests that hypothalamic and peripheral 5HT systems have a significant role in appetite regulation, possibly a homeostatic mechanism in regulating peripheral TRP levels. Methods: We examined the association between a polymorphism in intron 7 of TPH1, 218A N C and plasma total TRP levels in 118 patients with major depression. Results: There was an interaction between 218A N C and gender in determining plasma TRP whereby presence of the 218C allele, in women, was associated with markedly reduced plasma TRP. Limitations: The study investigated only the TRP1 gene and did not use a haplotype analysis. The results only apply to a population of subjects suffering from major depression. Conclusions: TPH1 may be associated with the regulation of peripheral tryptophan levels and therefore availability of tryptophan to the brain. This may have relevance to a range of neuropsychiatric conditions.
40. Tryptophan metabolism and immunogenetics in major depression
Brain, Behavior, and Immunity, 2009
the disease outcome in subordinate rats was related to behavioral differences: Intruder males that became clearly defeated during confrontations less frequently developed arthritis as compared to subordinates which rarely displayed submissive behaviors. Furthermore, we found a relationship between onset and severity of disease and aggressive behavior elements displayed by residents. These data suggest that the specific coping style of intruder males during social conflict-rather than subordination per se-is related to stress-induced influences on susceptibility, onset and severity of arthritic disease.
Tryptophan depletion and its implications for psychiatry
British Journal of Psychiatry, 2001
BackgroundOver the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems.AimsTo review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders.MethodSystematic review of preclinical and clinical studies.ResultsTryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar.ConclusionsThe findings that tryptophan depletion produces a relapse o...
Negative Effects of Latent Toxoplasmosis on Mental Health
Frontiers in Psychiatry
Infection by the parasite Toxoplasma, which affects about 33% of world population, is associated with an increased risk of several mental health disorders, the most strongly with schizophrenia. It is unknown whether schizophrenia is associated with this infection the most strongly, or whether this association has just been the most intensively studied for historical reasons. We used the data from 6,367 subjects tested for toxoplasmosis who took part in an internet survey to search for associations of these infections with 24 mental health disorders and evidence of otherwise impaired mental health. The typical symptom associated with toxoplasmosis was anxiety, and the typical toxoplasmosisassociated disorders were autism (OR = 4.78), schizophrenia (OR = 3.33), attention deficit hyperactivity disorder (OR = 2.50), obsessive compulsive disorder (OR = 1.86), antisocial personality disorder (OR = 1.63), learning disabilities (OR = 1.59), and anxiety disorder (OR = 1.48). Toxoplasmosis could play a substantial role in the etiopathogenesis of mental health disorders and its association with schizophrenia is the second strongest association, after autism.
Tryptophan depletion and depressive vulnerability
Biological Psychiatry, 1999
Background: Rapid and transient depletion of tryptophan (TRP) causes a brief depressive relapse in most patients successfully treated with and taking selective serotonin reuptake inhibitors, but little change in drug-free, symptomatic depressed patients. This study investigates the effects of TRP depletion in drug-free subjects in clinical remission from a prior major depressive episode (MDE). Methods: Twelve subjects with a prior MDE, currently in clinical remission and drug-free for at least 3 months (patients), and 12 healthy subjects without personal or family history of Axis I disorder (controls), received TRP depletion. The study was conducted in a double-blind, controlled [full (102-g) and quarter-strength (25 g) 15-amino acid drinks], crossover fashion. Behavioral ratings and plasma TRP levels were obtained prior to, during, and after testing. Results: All subjects experienced significant depletion of plasma TRP on both test-drinks, showing a significant dose-response relation. Healthy control subjects had minimal mood changes, but patients had a depressive response of greater magnitude. Conclusions: In the context of prior TRP depletion studies with antidepressant-treated, and drug-free symptomatic depressed patients, these results suggest that depression may be caused not by an abnormality of 5-HT function, but by dysfunction of other systems or brain regions modulated by 5-HT.