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Neurophysiological mechanisms of action on behavior by pathogens


Neurophysiological mechanisms of action on behavior by pathogens

Infections caused by viruses and other pathogens are capable of changing the behavior of living organisms.
Toxoplasma gondii is one such pathogen. T. gondii increases dopamine turnover in the brains of those affected, whereas ADHD is characterized by a dopamine (action) deficiency in the PFC and striatum.
T. gondii should probably be considered more as a model for the influence of pathogens on behavior than as a direct influencing factor in relation to ADHD. At the very least, T. gondii may play a role in the differential diagnosis of ADHD-HI. Infected humans show an increased entrepreneurial drive, infected rodents an increased risk-taking behavior and an attraction to cat urine.
T. gondii is thought to be linked to an increased risk of car accidents, mental illness, drug addiction and other behavioral disorders in humans.
T. gondii is found in 50 to 60 % of the population in Germany. The parasite reproduces exclusively in cats.
A T. gondii infection in the mother during pregnancy can increase the child’s risk of ADHD.

1. Toxoplasma gondii

1.1. Toxoplasma gondii alters behavior in humans and animals

It has long been known that the Toxoplasma gondii pathogen alters behavior in cats. However, a more recent study shows that an infection with Toxoplasma gondii also significantly alters the behavior of humans.1 T. gondii causes changes in several thousand genes and proteins and poses considerable health risks.2

People who are infected with Toxoplasma gondii showed

  • 1.8 times more likely to want to be self-employed as an entrepreneur1

Toxoplasma gondii has infected an estimated 20 to 30 % of the world’s human population.34 The regional prevalence varies between 9 % in Norway and 60 % in Brazil. The prevalence in women in Germany is 50 to 63 %.5 The prevalence in the respective population correlates

  • Positively with neuroticism6 and
  • Negatively with the institutional quality and economic performance of the respective countries7

The parasite reproduces exclusively in wild and domestic cats.1

In rodents, a T. gondii infection causes

  • Increased risk behavior in rats8910
  • An attraction to cat urine10
  • Greater exploration of new areas in labyrinths10
  • Less avoidance of open spaces10

In humans, T. gondii is suspected of being the cause of an increased risk of

  • Car accidents (2.65 times higher)11
  • Mental illnesses,12 such as schizophrenia (odds ratio 2.7)13
  • Neuroticism10
  • Drug addiction, especially alcohol12
  • Impulsiveness1415
  • Aggression15
  • Suicide1012

T. gondii causes changes in the production, metabolism or synthesis of

  • Hormones14
    • Increased testosterone161
      Increased testosterone is a possible cause of risk-taking behavior, aggressiveness and impulsivity in humans
  • Neurotransmitters
    • Serotonin
    • Dopamine,17 whereby T. gondii increases dopamine turnover in the brain.1819
    • Noradrenaline

1.2. Toxoplasma gondii and ADHD

The study situation on the question of whether T. gondii increases or decreases the risk of ADHD is inconsistent.

Infection of the mother during pregnancy has been associated with an increased risk of ADHD in the child.20
However, there is no evidence that this is due to the specific effect of T. gondii. Other infections of the mother during pregnancy also increase the child’s risk of ADHD, such as rubella, herpes simplex 2 or influenza.
Another study found no increased antibodies against T. gondii in ADHD sufferers.21 Another study found no statistical association between cat ownership by the parents before the birth of the child and ADHD in the child at the age of 10.22 However, the same study found a 2.23-fold increased risk of ADHD in boys whose mother kept a dog before birth. Girls were not affected.
A larger study found that toxoplasmosis correlated with a 1.5-fold risk of ADHD (OR 2.5).23

While Toxoplasma gondii increases dopamine metabolism in the brain, dopamine metabolism is typically reduced in ADHD. This could indicate that T. gondii is not a cause of ADHD.

It is theoretically conceivable that T. gondii could partially conceal existing ADHD, as T. gondii has a dopamine-increasing effect, whereas ADHD is characterized by a dopamine (effect) deficiency (among other things). This hypothesis could be supported by the results of a study according to which T gondii antibodies were found 25 % less frequently in ADHD sufferers than in non-affected persons.24 However, a meta-study of 7 studies came to no clear conclusion.25 A more recent study found a 2.8-fold risk of ADHD in adults with T. gondii seropositivity, increased IgG titer (serointensity) and higher anti-T. gondii IgG avidity. The severity of symptoms in those affected was increased. In particular, hyperactivity correlated with increased serointensity.26

2. Lactobacillus rhamnosus (JB-1)

Lactobacillus rhamnosus (JB-1) given to healthy mice increased the level of glutamate and glutamine by 10 % within 2 weeks, the level of N-acetylaspartate and N-acetylaspartylglutamic acid by 37 % and the level of GABA by 25 % within 4 weeks. Glutamate and glutamine levels remained elevated for 4 weeks after the end of treatment.
There were consistent changes in GABA-A and -B receptor subtypes in certain brain regions, which was associated with reduced anxiety and depression behavior.2728

  1. Johnson, Fitza, Lerner, Calhoun, Beldon, Chan, Johnson (2018): Risky business: linking Toxoplasma gondii infection and entrepreneurship behaviours across individuals and countries. Proc Biol Sci. 2018 Jul 25; 285(1883): 20180822. doi: 10.1098/rspb.2018.0822, PMCID: PMC6083268, PMID: 30051870, n = 1495

  2. Carter (2013): Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders. J Pathog. 2013;2013:965046. doi:10.1155/2013/965046

  3. Flegr (2013): How and why Toxoplasma makes us crazy. Trends Parasitol. 2013 Apr;29(4):156-63. doi: 10.1016/

  4. Su, Khan, Zhou, Majumdar, Ajzenberg, Dardé, Zhu, Ajioka, Rosenthal, Dubey, Sibley (2012): Globally diverse Toxoplasma gondii isolates comprise six major clades originating from a small number of distinct ancestral lineages. Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5844-9. doi: 10.1073/pnas.1203190109.

  5. Flegr, Prandota, Sovičková, Israili (2014): Toxoplasmosis – A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries. PLoS One. 2014; 9(3): e90203. doi: 10.1371/journal.pone.0090203. PMCID: PMC3963851. PMID: 24662942

  6. Lafferty (2006): Can the common brain parasite, Toxoplasma gondii, influence human culture? Proc Biol Sci. 2006 Nov 7;273(1602):2749-55.

  7. Maseland (2013): Parasitical cultures? The cultural origins of institutions and development. Journal of Economic Growth. June 2013, Volume 18, Issue 2, pp 109–136

  8. Berdoy, Webster, Macdonald (2000): Fatal attraction in rats infected with Toxoplasma gondii. Proc Biol Sci. 2000 Aug 7;267(1452):1591-4.

  9. Tan, Vyas (2016): Toxoplasma gondii infection and testosterone congruently increase tolerance of male rats for risk of reward forfeiture. Horm Behav. 2016 Mar;79:37-44. doi: 10.1016/j.yhbeh.2016.01.003.

  10. Lafferty (2006): Can the common brain parasite, Toxoplasma gondii, influence human culture? Proc Biol Sci. 2006 Nov 7;273(1602):2749-55.

  11. Flegr, Havlícek, Kodym, Malý, Smahel (2002): Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study. BMC Infect Dis. 2002 Jul 2;2:11.

  12. Samojłowicz, Borowska-Solonynko, Kruczyk (2017): New, previously unreported correlations between latent Toxoplasma gondii infection and excessive ethanol consumption. Forensic Sci Int. 2017 Nov;280:49-54. doi: 10.1016/j.forsciint.2017.09.009.

  13. Torrey, Bartko, Yolken (2012): Toxoplasma gondii and other risk factors for schizophrenia: an update. Schizophr Bull. 2012 May;38(3):642-7. doi: 10.1093/schbul/sbs043.

  14. Peng, Brenner, Mathai, Cook, Fuchs, Postolache, Groer, Pandey, Mohyuddin, Giegling, Wadhawan, Hartmann, Konte, Brundin, Friedl, Stiller, Lowry, Rujescu, Postolache (2018): Moderation of the relationship between Toxoplasma gondii seropositivity and trait impulsivity in younger men by the phenylalanine-tyrosine ratio. Psychiatry Res. 2018 Dec;270:992-1000. doi: 10.1016/j.psychres.2018.03.045.

  15. Cook, Brenner, Cloninger, Langenberg, Igbide, Giegling, Hartmann, Konte, Friedl, Brundin, Groer, Can, Rujescu, Postolache (2015): “Latent” infection with Toxoplasma gondii: association with trait aggression and impulsivity in healthy adults. J Psychiatr Res. 2015 Jan;60:87-94. doi: 10.1016/j.jpsychires.2014.09.019.

  16. Abdoli, Dalimi (2014): Are There any Relationships between Latent Toxoplasma gondii Infection, Testosterone Elevation, and Risk of Autism Spectrum Disorder? Front Behav Neurosci. 2014; 8: 339. doi: 10.3389/fnbeh.2014.00339, PMCID: PMC4173877, PMID: 25309376

  17. Stock, Dajkic, Köhling, von Heinegg, Fiedler, Beste (2017): Humans with latent toxoplasmosis display altered reward modulation of cognitive control. Sci Rep. 2017 Aug 31;7(1):10170. doi: 10.1038/s41598-017-10926-6.

  18. Prandovszky, Gaskell, Martin, Dubey, Webster, McConkey (2011): The Neurotropic Parasite Toxoplasma Gondii Increases Dopamine Metabolism. PLoS One. 2011; 6(9): e23866. doi: 10.1371/journal.pone.0023866. PMCID: PMC3177840. PMID: 21957440

  19. Stibbs (1985): Changes in brain concentrations of catecholamines and indoleamines in Toxoplasma gondii infected mice. Ann Trop Med Parasitol. 1985 Apr;79(2):153-7.

  20. Bekdas, Tufan, Hakyemez, Tas, Altunhan, Demircioglu, Kısmet (2014): Subclinical immune reactions to viral infections may correlate with child and adolescent diagnosis of attention-deficit/hyperactivity disorder: a preliminary study from Turkey. Mervan. Afr Health Sci. 2014 Jun; 14(2): 439–445. doi: 10.4314/ahs.v14i2.21. PMCID: PMC4196392. PMID: 25320595

  21. Khademvatan, Riahi, Izadi-Mazidi, Khajeddin, Yousefi (2018): Toxoplasma gondii Exposure and the Risk of Attention Deficit Hyperactivity Disorder in Children and Adolescents. Pediatr Infect Dis J. 2018 Nov;37(11):1097-1100. doi: 10.1097/INF.0000000000001985. n = 200

  22. Cassidy-Bushrow, Sitarik, Johnson-Hooper, Phillips, Jones, Johnson, Straughen (2019): Prenatal pet keeping and caregiver-reported attention deficit hyperactivity disorder through preadolescence in a United States birth cohort. BMC Pediatr. 2019 Oct 29;19(1):390. doi: 10.1186/s12887-019-1719-9. n = 627 Familien

  23. Flegr J, Horáček J. Negative Effects of Latent Toxoplasmosis on Mental Health. Front Psychiatry. 2020 Feb 18;10:1012. doi: 10.3389/fpsyt.2019.01012. PMID: 32132937; PMCID: PMC7040223.

  24. Khademvatan, Riahi, Izadi-Mazidi, Khajeddin, Yousefi (2018): Toxoplasma gondii Exposure and the Risk of Attention Deficit Hyperactivity Disorder in Children and Adolescents. Pediatr Infect Dis J. 2018;37(11):1097-1100. doi:10.1097/INF.0000000000001985

  25. Nayeri, Sarvi, Moosazadeh, Hosseininejad, Amouei, Daryani (2020): Toxoplasma gondii Infection and risk of attention-deficit hyperactivity disorder: a systematic review and meta-analysis. Pathog Glob Health. 2020;114(3):117-126. doi:10.1080/20477724.2020.1738153

  26. Lam, de Sordi, Müller, Lam, Carl, Kohse, Philipsen1 (2020): Aggravation of symptom severity in adult attention-deficit/hyperactivity disorder by latent Toxoplasma gondii infection: a case–control study. Sci Rep. 2020; 10: 14382. doi: 10.1038/s41598-020-71084-w PMCID: PMC7463265 PMID: 32873854

  27. Janik, Thomason, Stanisz, Forsythe, Bienenstock, Stanisz (2016): Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate. Neuroimage. 2016 Jan 15;125:988-995. doi: 10.1016/j.neuroimage.2015.11.018.

  28. Scott, Clarke, Dinan (2013): The brain-gut axis: a target for treating stress-related disorders. Mod Trends Pharmacopsychiatry. 2013;28:90-9. doi: 10.1159/000343971.

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