Neurophysiological mechanisms of action on behavior by pathogens.
Infections by viruses and other pathogens are capable of altering the behavior of living beings.
Toxoplasma gondii is such a pathogen. T. gondii increases dopamine turnover in the brain of affected individuals, whereas in ADHD there is a dopamine (effect) deficiency in the PFC and striatum.
T. gondii should probably be considered more as a model for how pathogens influence behavior than as a direct influencing factor in relation to ADHD. However, it is conceivable that T. gondii (especially in ADHD-HI with hyperactivity) could cause unfavorable behavioral summations that could be dysfunctional to a particular degree as a result. At least for the differential diagnosis of ADHD-HI, T. gondii might play a role.
- 1. Toxoplasma gondii
- 2. Lactobacillus rhamnosus (JB-1)
1. Toxoplasma gondii
1.1. Toxoplasma gondii alters behavior in humans and animals
It has been known for some time that the pathogen Toxoplasma gondii alters behavior in cats. However, a 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 or proteins and considerable health risks.2
People infected with Toxoplasma gondii showed
- 1.8 times more likely to aspire to be entrepreneurially self-employed1
Toxoplasma gondii has infected an estimated 20% to 30% of the world’s human population.34 Regional prevalence varies from 9% in Norway to 60% in Brazil. The prevalence in females ranges from 50% to 63% in Germany.5 The prevalence in each 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, T. gondii infection causes
- An increased risk behavior in rats8910
- An attraction to cat urine10
- A greater exploration of new areas in labyrinths10
- A lower avoidance of open spaces10
In humans, T. gondii is suspected to be the cause of an increased risk of
- Car accidents (2.65 times increased)11
- Mental illness,12 such as schizophrenia (odds ratio 2.7)13
- Drug addiction, especially alcohol12
T. gondii causes changes in the production, metabolism, or synthesis of
1.2. Toxoplasma gondii and ADHD
Studies on whether T. gondii increases or decreases the risk of ADHD are inconsistent.
Maternal infection during pregnancy has been associated with an increased risk of ADHD in the child.20
However, it has not been proven that this is due to the specific effect of T. gondii. Other infections of the mother during pregnancy also increase the ADHD risk of the child, such as rubella, herpes simplex 2 or influenza.
Another study found no increased antibodies to T. gondii in ADHD sufferers.21 Another study found no statistical association between cat ownership by parents before the child’s birth and ADHD in the child at age 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 decreased in ADHD. This may indicate that T. gondii is not a cause of ADHD.
It is theoretically conceivable that T. gondii could partially mask an existing ADHD, since T. gondii has a dopamine-increasing effect, whereas in ADHD there is (among other things) a dopamine (effect) deficiency. This hypothesis could be supported by results of a study that found T- gondii antibodies 25% less frequently in ADHD sufferers than in nonaffected individuals.24 In contrast, a metastudy of 7 studies did not reach a clear conclusion.25 A recent study found a 2.8-fold risk of ADHD in adults with T. gondii seropositivity, increased IgG titer (serointensity), and stronger anti-T. gondii IgG avidity. Symptom severity in affected individuals 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% and the level of N-acetylaspartate and N-acetylaspartylglutamic acid by 37% within 2 weeks 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 specific brain regions, which was associated with decreased anxiety and decreased depressive behavior.2728
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 ↥ ↥ ↥ ↥
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 ↥
Flegr (2013): How and why Toxoplasma makes us crazy. Trends Parasitol. 2013 Apr;29(4):156-63. doi: 10.1016/j.pt.2013.01.007. ↥
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. ↥
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 ↥
Lafferty (2006): Can the common brain parasite, Toxoplasma gondii, influence human culture? Proc Biol Sci. 2006 Nov 7;273(1602):2749-55. ↥
Maseland (2013): Parasitical cultures? The cultural origins of institutions and development. Journal of Economic Growth. June 2013, Volume 18, Issue 2, pp 109–136 ↥
Berdoy, Webster, Macdonald (2000): Fatal attraction in rats infected with Toxoplasma gondii. Proc Biol Sci. 2000 Aug 7;267(1452):1591-4. ↥
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. ↥
Lafferty (2006): Can the common brain parasite, Toxoplasma gondii, influence human culture? Proc Biol Sci. 2006 Nov 7;273(1602):2749-55. ↥ ↥ ↥ ↥ ↥ ↥
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. ↥
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. ↥ ↥ ↥
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. ↥
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. ↥ ↥
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. ↥ ↥
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 ↥
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. ↥
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 ↥
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. ↥
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 ↥
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 ↥
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 ↥
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. ↥
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 ↥
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 ↥
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 ↥
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. ↥
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. ↥