Can Cats trigger self harm behaviour in humans? Arch.Gen.Psych. Nov,2012

08.11.2012

Toxoplasma gondii is a widespread  parasite affecting approximately one-third of people world- wide. Cats are the definitive hosts and humans are infected by ingestion of oocysts.  Parasite hides in neurones and muscle cells. Symptoms range from none to minimal in the most common cases, to severe in rare cases.Immune system fails to eradicate the infestation.The parasites are found in brain including  amygdala and prefrontal cortex.

An association  of  this infection with schizophrenia is consistently reported. (Torrey et al 2007. Schizophr Bull. 2007;33(3):729- 736).  Women with a high level of IgG antibodies have a significantly elevated risk of developing schizophrenia spectrum disorders.( reported in the same cohort as present study by Pedersen  et al Am J Psychiatry. 2011;168(8):814-821).  Arling et al ,209 found greater titers of T gondi IgG antibodies in patients with mood disorders who attempted suicide as compared with both patients with mood disorders who did not attempt suicide and healthy controls. A significant relationship between T gondii infection and suicidal self-directed violence in younger patients  independent of symptom severity or antipsychotic dosage was reported by Okusaga et al in 2011.

Present study: Pregnant women living in 5 counties in Denmark from 1992 to 1995 were offered to have their child screened for T gondii shortly after birth. These mothers ,whose children were screened for T gondii constitute the study population. IgG levels in blood from the newborn were measured.Mothers of children with an IgG level more than 24 were regarded as T gondii positive from the time of delivery.(The IgG antibodies measured in the blood from the child were maternal in origin).For one  fourth of the women (n = 12 740) in the study population, data were also available on IgG level based on the first-trimester serum sample.Danish Cause of Death Register ( data on suicide), the Danish National Hospital Register (data on patients treated in general hospitals and their outpatients) and  the Danish Psychiatric Central Research Register ( data on  all admissions to psychiatric inpatient and outpatient facilities)  provided all the data required.

Findings:

Among the 45 271 mothers studied from delivery until 2006, 488 had a first contact for self-directed violence during the 595 306 person-years at risk, corresponding to a crude incidence rate of 8.20 per 10 000 person- years. Mothers who were T gondii sero positive had a 1.53-fold (95% CI, 1.27-1.85; P<.001) significant relative risk of self- directed violence compared with T gondii–sero negative mothers.

Risk of self-directed violence seemed to increase with increasing IgG level

Among women with self-directed violence prior to delivery, sero positive women had a relative risk of self-directed violence after delivery of 1.54 (95% CI, 0.98-2.39; P = .06) compared with sero negative women.

Women who were sero positive had a relative risk of a violent suicide attempt of 1.81 (95% CI, 1.13-2.84; P = .01) compared with sero negative women.

The results indicate a predictive association between T gondii IgG antibody titers shortly after delivery and self-directed violence in later life. It is consistent with other studies from Turkey (Yagmur et al 2010) Maryland (Arling et al 2009) and Germany (Okusaga, 2011).

How?

1. Immune/inflammatory mechanism: Many Studies report that suicide attempters have high interleukin 6 (IL-6) and tumor necrosis factor. These are elevated in T Gondii infection also.Pro inflammatory cytokines activate the enzyme indolamine 2,3- dioxygenase (IDO) resulting in degradation of tryptophan toward kynurenines and a relative tryptophan deprivation state. The Kinurenine metabolites kynurenic acid and quinolinic acid are  potent neuromodulators of the NMDA receptor. Kynurenic acid concentrations in the CSF  is reported in some studies as associated with violent suicide attempts.

2.One could argue that pre existing immune abnormalities might have lead to increased T gondii infection as well as increased suicidal behaviour. Longitudinal studies can only answer this issue.

Limitations:

1. Even though T gondi titres were measured before the self harm behaviour, the observed association cannot be interpreted as causal.It is possible that people with psychiatric distur- bances might have  a higher risk of becoming T gondii infected prior to contact with the health system. ( for eg  consumption of raw or undercooked meat, incompletely washed fruits and vegetables, cleaning the cat litter box, and washing the kitchen knives infrequently after preparation of raw meat, prior to handling another food item).

2.The cohort excluded men and nulliparous women who may have different risk factors for self-directed violence.

3. The data from registers had limitations: It was not always possible to conclude whether nonfatal self-directed violence was suicidal or non- suicidal.

This is the largest study of  T Gondii infection and self directed violence with complete follow up data for 14 years .The observations are consistent with previous studies.

Clinical practice:
Is the level of evidence enough for looking for T gondii in our suicidal patients?
Trials of  Azithromycin, (Dickerson 2007), Trimethoprim (Shibre,2010) Artemisinin, (Dickerson, 2011) by adding these medication to regular antipsychotics in patients with schizophrenia who are  sero positive for T Gondii, did not show any significant benefit.Also, there is no medication that is effective in the cyst stage of the organism (in brain and muscles).
summary of the article
Toxoplasma gondii Infection and Self-directed Violence in Mothers.Pedersen MG, Mortensen PB, Norgaard-Pedersen B, Postolache TT.Arch Gen Psychiatry. Nov.2012

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