A virus that increases intelligence, and what else?

 

Caterpillar infected by baculovirus, before liquefaction (Wikicommons, Williams et al. 2017)

 

Higher IQ is associated with antibodies to cytomegalovirus, but only in adults whose IQ is already above a certain level. Which is the cause, and which is the effect?

 

Cytomegalovirus (CMV) belongs to the herpes family and is spread by contact with bodily fluids. Around 45 to 100% of the population may be infected, although most hosts are unaware that they are infected. It has one of the largest genomes among human viruses, a sign perhaps of its ability to manipulate its host:

 

With millions of years of coevolution within their hosts, CMVs, like other herpesviruses, encode numerous proteins that can broadly influence the magnitude and quality of both innate and adaptive immune responses. These viral proteins include both homologues of host proteins, such as MHC class I or chemokine homologues, and proteins with little similarity to any other known proteins, such as the chemokine binding protein. Although a strong immune response is launched against CMV, these virally encoded proteins can interfere with the host's ability to efficiently recognize and clear virus, while others induce or alter specific immune responses to benefit viral replication or spread within the host. (Miller-Kittreall and Sparer 2009)

 

CMV infection at birth leads to mental retardation (Andreou et al. 2021). Recently, however, it has been shown that infection later in life can lead to higher IQ. This is one of three findings from a Norwegian study on IQ and antibodies to CMV in adults. The study showed that CMV seropositivity was significantly associated with higher IQ in men who suffered from bipolar spectrum disorders and with lower IQ in women who suffered from schizophrenia spectrum disorders. CMV seropositivity was not associated with IQ in healthy controls (Andreou et al. 2021). The study’s authors were at a loss to explain the association between CMV seropositivity and higher IQ in bipolar men, all the more so because the number of bipolar men was small, only 35.

 

An association between CMV and IQ has now been found in healthy individuals. A Czech study has shown that IQ, especially verbal IQ, is higher in people with antibodies to CMV. Moreover, the IQ advantage decreases with decreasing levels of CMV antibodies, i.e., with increasing time since the CMV infection (Chvatálova et al. 2022).

 

Why do healthy Czechs show this association but not healthy Norwegians? It’s not because the Czechs were a larger sample. In fact, the Czech sample had 283 healthy individuals, and the Norwegian sample 474. The two samples did differ, however, in educational attainment. The Czechs were biology students at a university in Prague, whereas the Norwegians were randomly recruited from the Norwegian population register. The latter were also described as “Caucasians” living in Oslo. Oslo’s population is almost one third of immigrant origin, with Pakistanis forming the largest immigrant group. There are also large numbers of people from Sri Lanka, Turkey, Morocco, and Iraq (Wikipedia 2022). 

 

The last point would not be problematic if cognitive evolution had ended long ago among the common ancestors of Europeans, Middle Easterners, and South Asians. There is mounting evidence, however, for cognitive evolution in recent times. Ashkenazi Jews seem to have gained their cognitive advantage during the past 1,000 or so years, and the same seems to be true for the Parsis (Cochran et al. 2006; Dunkel et al. 2019; Frost 2021). There is even evidence for significant cognitive evolution in communities that are not normally thought of as ethnic groups, such as French Canadians in regions where British and American traders were historically few in number (Frost 2012).

 

Why does CMV seropositivity correlate with higher IQ?

 

The authors of the Czech study suggest that more intelligent people have more social contacts and are thus more likely to catch the virus: “we suggest that more intelligent subjects who have more social and sexual contacts—CMV is transmitted by close contacts, e.g. by kissing—might have a higher risk of encountering a CMV infection.” Yet there is no evidence that smarter people are more extraverted. In fact, they tend to be loners, if only because they have fewer people of their intellectual level to hang out with. The academic consensus seems to be that neither introversion nor extraversion correlates with intelligence (Saklofske and Kostura 1990).

 

Could the arrow of causality run in the other direction? Is it possible that CMV makes its host smarter? The authors reject that explanation because congenital CMV infection reduces intelligence. But maybe the effect is different in adults.

 

If CMV does increase the intelligence of adult hosts, the effect would be confined to those whose IQ is already above a certain level. The above two studies showed a significant increase only among university students, and not in a more mixed population with varying levels of educational attainment. But why did the latter study show significantly higher IQ in men with bipolar disorders and significantly lower IQ in women with schizophrenia? For the answer, we can turn to the results of a recent genome-wide association study: most of the alleles for schizophrenia are associated with lower intelligence, and most of the alleles for bipolar disorder are associated with higher intelligence (Smeland et al. 2020). Those results are partially confirmed by the findings of a prospective cohort study: “at least in men, high intelligence may indeed be a risk factor for bipolar disorder, but only in the minority of cases who have the disorder in a pure form with no psychiatric comorbidity” (Gale et al. 2013).

 

Behavior alteration?

 

Why would a virus try to make its host smarter? What would it gain? Perhaps the increase in intelligence is a side-effect. Perhaps the virus is trying to improve its chances of spreading to new hosts by altering the behavior of its current host (Cochran et al. 2000; Frost 2020).

 

Although behavior is more often altered by larger and more complex pathogens, particularly fungi, there are many viruses that engage in behavior alteration. For example, viruses from the baculoviridae family will infect a caterpillar and make it hyperactive to spread their viral progeny over a wider area. Or the caterpillar will be made to climb to the top of a plant and dissolve itself through overproduction of enzymes, thus becoming a mass of tasty goo for ingestion by potential hosts (Han et al. 2015; Williams et al. 2017). Rabies is another behavior-altering virus: it makes its host more aggressive and thus more likely to bite potential hosts.

 

Although CMV infects a wide range of people, it seems to target a smaller subgroup for behavior alteration, i.e., individuals with intelligence above a certain threshold, and men more than women. If we look at the epidemiological data, we see that male homosexuals are especially susceptible. A study at a venereal disease clinic found that antibodies to CMV were present in 94% of the male homosexual patients and 54% of the male heterosexual patients. “The data suggest that sexual transmission is an important mode of spread of CMV among adults and that homosexual men are at greater risk for CMV infections than are heterosexual men” (Drew et al. 1981). Another study has identified passive anal sex as the most effective means of transmission: “Of seven sexual practices investigated, only passive anal-genital intercourse correlated with the acquisition of cytomegalovirus infection (p =0.008)” (Mintz et al. 1983).

 

Which is the cause and which is the effect? Does passive anal sex facilitate CMV infection? Or does CMV infection facilitate the desire for passive anal sex? The answer may be ‘yes’ to both questions. Sometimes ‘the cause’ and ‘the effect’ are two sides of the same coin.

 

This virus may indeed be the ‘gay germ’ that Greg Cochran has written about. Or one of them. Male homosexuality probably has several causes, and the microbial cause probably involves more than one pathogen.

 

 

References

 

Andreou, D., K.N. Jørgensen, L.A. Wortinger, K. Engen, A. Vaskinn, T. Ueland, R.H. Yolken, O.A. Andreassen, and I. Agartz. (2021). Cytomegalovirus infection and IQ in patients with severe mental illness and healthy individuals. Psychiatry Research 300:113929. https://doi.org/10.1016/j.psychres.2021.113929  

 

Chvatálová, V., B. Šebánková, H. Hrbáčková, P. Tureček, L. Příplatová, and J. Flegr. (2022). Differences in cognitive performance between cytomegalovirus-infected and cytomegalovirus-free students. PsyArXiv, 5 May 2022. https://doi.org/10.31234/osf.io/jbvky  

 

Cochran, G.M., P.W. Ewald, and K.D. Cochran. (2000). Infectious Causation of Disease: An Evolutionary Perspective. Perspectives in Biology and Medicine 43 (3): 406-48.

https://doi.org/10.1353/pbm.2000.0016  

 

Cochran, G., J. Hardy, and H. Harpending. (2006). Natural history of Ashkenazi intelligence. Journal of Biosocial Science 38: 659-693, https://doi.org/10.1017/S0021932005027069  

 

Drew, W.L., L. Mintz, R.C. Miner, M. Sands, and B. Ketterer. (1981). Prevalence of Cytomegalovirus Infection in Homosexual Men. The Journal of Infectious Diseases 143(2): 188–192. https://doi.org/10.1093/infdis/143.2.188

 

Dunkel, C.S., M.A. Woodley of Menie, J. Pallesen, and E.O.W. Kirkegaard. (2019). Polygenic scores mediate the Jewish phenotypic advantage in educational attainment and cognitive ability compared with Catholics and Lutherans. Evolutionary Behavioral Sciences 13(4): 366-375. https://doi.org/10.1037/ebs0000158  

 

Frost, P. (2012). Tay-Sachs and French Canadians: A case of gene-culture co-evolution? Advances in Anthropology 2(3): 132-138. http://dx.doi.org/10.4236/aa.2012.23016  

 

Frost, P. (2020). Are Fungal Pathogens Manipulating Human Behavior? Perspectives in Biology and Medicine 63(4): 591-601. https://doi.org/10.1353/pbm.2020.0059   

 

Frost, P. (2021). Commentary on Fuerst et al: Do Human Populations Differ in Their Mental Characteristics? Mankind Quarterly 62(2). http://doi.org/10.46469/mq.2021.62.2.9  

 

Gale, C., G. Batty, A. McIntosh. et al. (2013). Is bipolar disorder more common in highly intelligent people? A cohort study of a million men. Molecular Psychiatry 18: 190–194. https://doi.org/10.1038/mp.2012.26  

 

Han, Y., S. van Houte, G.R. Drees, M.M. van Oers, and V.I. Ros. (2015). Parasitic Manipulation of Host Behaviour: Baculovirus SeMNPV EGT Facilitates Tree-Top Disease in Spodoptera exigua Larvae by Extending the Time to Death. Insects 6(3): 716–731. https://doi.org/10.3390/insects6030716  

 

Miller-Kittrell, M., and T.E. Sparer. (2009). Feeling manipulated: cytomegalovirus immune manipulation. Virology Journal 6: 4 (2009). https://doi.org/10.1186/1743-422X-6-4  

 

Mintz, L., W.L. Drew, R.C. Miner, and E.H. Braff. (1983). Cytomegalovirus infections in homosexual men. An epidemiological study. Annals of Internal Medicine 99(3):326-9. https://doi.org/10.7326/0003-4819-99-3-326

 

Saklofske, D. H., and D.D. Kostura. (1990). Extraversion-introversion and intelligence. Personality and Individual Differences 11(6): 547-551. https://doi.org/10.1016/0191-8869(90)90036-Q  

 

Smeland, O.B., S. Bahrami, O. Frei, A. Shadrin, K. O'Connell, J. Savage, K. Watanabe, F. Krull, F. Bettella, N.E. Steen, T. Ueland, D. Posthuma, S. Djurovic, A.M. Dale, and O.A. Andreassen. (2020). Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence. Molecular Psychiatry 25(4):844-853. https://doi.org/10.1038/s41380-018-0332-x  

 

Williams, T., C. Virto, R. Murillo, and P. Caballero. (2017). Covert Infection of Insects by Baculoviruses. Frontiers in Microbiology 17(8): 1337. https://doi.org/10.3389/fmicb.2017.01337

 

Wikipedia (2022). Oslo – Demographics. https://en.wikipedia.org/wiki/Oslo#Demographics

Red-haired women are special

The Damsel of the Sanct Grael – Dante Gabriel Rossetti (1828-1882)

It's known that red-haired women, but not red-haired men, are more sensitive to pain. Red hair is also associated with a higher risk of developing endometriosis, Parkinson's disease, and decreased platelet function.

A study in the latest issue of PLoS One has confirmed that red hair, especially in women, is linked to certain health issues. According to a survey of over seven thousand participants, red-haired women do worse than other women in ten health categories and better in only three, being especially prone to colorectal, cervical, uterine, and ovarian cancer. Red-haired men seem to be as healthy as other men, doing better in three categories and worse in three. Reproductive success, i.e., number of children, is the only category where redheads of both sexes do better than other participants.

This study has also confirmed that red hair is naturally more frequent in women than in men. To a lesser degree, the same is true for blond hair and green eyes. These bright colors seem to result from a selection pressure that mainly targeted women, i.e., sexual selection. In other words, among early Europeans there were too many women and not enough men; hence, competition between women for mates favored those who could better catch the attention of men, such as through a palette of bright hair and eye colors.

Because women are overrepresented among redheads, it may be that estrogen promotes synthesis of red pigments by hair follicles, particularly during fetal development. Thus, if a baby is born red-haired and female, estrogenization of its body tissues should be, on average, near the top end of the normal range. It will therefore be more at risk of developing certain health issues.

Another hypothesis can be put forward. If red hair was the last hair color to evolve, the underlying alleles may not have finished adapting to the rest of the genome, and vice versa. This reciprocal adaptation is all the more necessary because one of the five alleles for red hair seems to be of Neanderthal origin. The hypothesis of incomplete adaptation does not exclude the hypothesis of high estrogenization. In fact, there may be interaction between the two factors. Although it's likely that sexual selection did produce new hair and eye colors, we must still explain why, in this palette of colors, red hair seems to show the greatest difference between men and women both in population frequency and in associated health effects. 

Reference

Frost P, Kleisner K, Flegr J (2017) Health status by gender, hair color, and eye color: Red-haired women are the most divergent. PLoS ONE 12(12): e0190238. 

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190238

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La rousse est particulière

On sait que les rousses, mais pas les roux, sont plus sensibles que les autres à la douleur. La rousseur est également associée à un plus grand risque de développer l'endométriose, la maladie de Parkinson, ainsi que des troubles de l'agrégation plaquettaire.

Une étude publiée dans le dernier numéro de la revue PLoS ONE confirme que la rousseur, surtout chez la femme, est reliée à certains problèmes de santé. Selon une enquête menée auprès de plus de sept mille participants, les rousses se classent pire que les autres femmes dans dix catégories de santé et mieux dans seulement trois, étant surtout susceptibles de développer des cancers du gros intestin, du col utérin, de l'utérus ou des ovaires. Quant aux roux, leur état de santé ressemble à celui des autres hommes : mieux dans trois catégories et pire dans trois. Le succès reproducteur, soit le nombre d'enfants, est la seule catégorie où les têtes rouges des deux sexes font mieux que les autres participants.

Cette étude confirme également que la rousseur est naturellement plus fréquente chez la femme que chez l'homme. Dans une moindre mesure,  c'est le même constat avec la blondeur et les yeux verts. Ces couleurs vives semblent être le résultat d'une pression de sélection visant surtout la femme, soit la sélection sexuelle. Autrement dit, il y aurait eu trop de femmes et pas assez d'hommes chez les premiers Européens, avec pour résultat une concurrence entre les femmes favorisant celles qui attiraient mieux les regards des hommes, comme par exemple par une palette de couleurs vives décorant les cheveux et les yeux.

Les femmes étant surreprésentées parmi les têtes rouges, on peut émettre l'hypothèse que l'œstrogène favorise la synthèse de pigments rouges dans les follicules pileux, particulièrement au cours du développement fœtal. Alors, si un enfant nait à la fois roux et de sexe féminin, l'œstrogénisation de ses tissus organiques doit être, en moyenne, vers la limite supérieure de la normale. La rousse sera donc plus à risque de connaitre certains problèmes de santé.

Une autre hypothèse est possible. Si la rousseur a été la dernière couleur de cheveux à paraître, il se peut que les allèles sous-jacents n’aient pas encore fini de s'adapter au reste du génome et vice versa. Cette adaptation réciproque est d'autant plus nécessaire parce que l'un des cinq allèles pour la rousseur semble être d'origine néandertalienne. Notons que l'hypothèse d'adaptation incomplète n'exclut pas celle de forte œstrogénisation. En fait, il pourrait y avoir une interaction entre les deux facteurs. S'il est vraisemblable que la sélection sexuelle ait produit de nouvelles couleurs des cheveux et des yeux, il faudra toujours expliquer pourquoi, dans cette palette de couleurs, la rousseur semble montrer la plus grande différence entre les hommes et les femmes, autant en termes de fréquence dans la population que sur le plan de la santé. 

Brainwashed by a microbe?

Toxoplasma gondii (source: A.J. Cann)

It’s long been known that many organisms are parasites, i.e., they survive by living off a host. In recent years we’ve learned that some of them can improve on their life strategy by manipulating their host’s behavior. A fungus, Ophiocordyceps unilateralis, will invade an ant’s brain and direct its host to go to the right height above ground, lock itself into position … and die (Ophiocordycepsunilateralis, 2013). A tapeworm, Schistocephalus solidus, will infect a fish and cause its host to turn white and prefer the water surface, thereby making it an easy prey for a passing bird—the next stage in the worm’s life cycle (Fish diseases and parasites, 2013). A protozoan, Toxoplasma gondii, after being excreted in cat feces and then picked up by a mouse, will infiltrate the brain of its new host and neutralize the fear response to the smell of cat urine. The host thus becomes a way to get back into a cat’s gut—the only place where this protozoan can sexually reproduce (Ingram et al., 2013). 

Ants, fish, mice … The sequence is troubling. What about us? Have some microbes evolved to manipulate our brains? Perhaps, but it would be hard to prove. For one thing, we’re continually being infected by seemingly benign microbes that trigger no symptoms of infection, i.e., fever, pus formation, immune response, etc. They go about their business without our knowing they’re inside us.

For another thing, a microbe can permanently alter our mental wiring and then be removed from our body. The culprit vanishes from the scene of the crime and leaves only a few ambiguous clues. This is the conclusion of a recent study on Toxoplasma gondii. When mice were infected with a weakened strain of this protozoan, they were able to overcome the infection and clear all traces of it from their brains. Yet the behavioral change remained:

[…] our data indicate that infection with all three major North American T. gondii clonal lineages results in loss of innate, hard-wired aversion to feline predator urine in mice. […] permanent interruption of mouse innate aversion to feline urine is a general trait of T. gondii infection that occurs within the first three weeks, independent of parasite persistence and ongoing brain inflammation. (Ingram etal., 2013)

It seems that T. gondii moves around the host’s brain and alters many neurons without actually taking up residence in them, apparently by injecting specific proteins through the cell wall.

Although we’re not a natural host, T. gondii does appear to alter human behavior: 

Toxoplasma-infected subjects differ from uninfected controls in the personality profile estimated with two versions of Cattell’s 16PF, Cloninger’s TCI and Big Five questionnaires. Most of these differences increase with the length of time since the onset of infection, suggesting that Toxoplasma influences human personality rather than human personality influencing the probability of infection. Toxoplasmosis increases the reaction time of infected subjects, which can explain the increased probability of traffic accidents in infected subjects reported in three retrospective and one very large prospective case-control study. […] Toxoplasma-infected male students are about 3 cm taller than Toxoplasma-free subjects and their faces are rated by women as more masculine and dominant. These differences may be caused by an increased concentration of testosterone. Toxoplasma also appears to be involved in the initiation of more severe forms of schizophrenia. At least 40 studies confirmed an increased prevalence of toxoplasmosis among schizophrenic patients. Toxoplasma-infected schizophrenic patients differ from Toxoplasma-free schizophrenic patients by brain anatomy and by a higher intensity of the positive symptoms of the disease. (Flegr, 2013)

T. gondii is being studied for possible behavioral effects mainly because it has attracted so much attention. But we’re probably being manipulated by other parasites. “A large number of parasitic organisms probably exist in helminths, protozoa, fungi, bacteria, archea and viruses that may influence the phenotype of their human host even more than the Toxoplasma. These organisms are, however, still waiting for research teams to engage in a systematic study of their influence on the human host” (Flegr, 2013).

Where to look? Cherchez la femme. Sexually transmitted diseases have much to gain from altering host behavior. I would especially look at bacterial vaginosis, chlamydia, and vaginal yeast.

References 

Fish diseases and parasites. (2013). Wikipedia

http://en.wikipedia.org/wiki/Fish_diseases_and_parasites

Flegr, J. (2013). Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma–human model in studying the manipulation hypothesis, The Journal of Experimental Biology, 216, 127-133. http://jeb.biologists.org/content/216/1/127.full 

Ingram, W.M., L.M. Goodrich, E.A. Robey, and M.B. Eisen (2013). Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance. PLoS ONE 8(9): e75246. doi:10.1371/journal.pone.0075246

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075246

Ophiocordyceps unilateralis. (2013). Wikipedia

http://en.wikipedia.org/wiki/Ophiocordyceps_unilateralis#Anti-zombie-fungus_fungus