Can a virus make you smarter?

What is your IQ? (… and do you have Toxoplasmosis?)

Cytomegalovirus is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae. Humans and monkeys serve as natural hosts. The 11 species in this genus include human betaherpesvirus 5, which is the species that infects humans. 

https://evoandproud.blogspot.com/2022/05/a-virus-that-increases-intelligence-and.html

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