Candida and autism

Shamanic ritual (Wikipedia - Idries Shah). There is a correlation between autism and antibodies for Candida albicans. Does a pathogenic strain of this yeast promote the development of autism? Cui bono?


In my previous posts I've argued that certain pathogens have acquired the capacity to manipulate human behavior. Humans are an interesting target for several reasons:

1. The human mind oversees an extensive range of complex behaviors

2. Humans are long-lived, thus providing a useful vehicle for spreading to other potential hosts.

3. Humans have particularly long generation times and are thus less able to develop resistance to short-generation pathogens, which can more easily “outmanoeuvre” the evolution of human resistance.

Among animal hosts in general, behavior can be manipulated by many pathogens, including fungi. Fungi seem to be better able than viruses and bacteria at producing and coordinating the array of chemicals needed for the targeted neural tissue. One of them may be Candida, a genus of yeasts that most often live in the gut but can be found elsewhere in the body. In particular, there seems to be a connection between their presence and the development of autism spectrum disorders (ASD):

We aimed to determine if children with ASD exhibit elevations in antibodies that target C. albicans, indicating current or previous overgrowth of this fungal species. [...] Plasma anti-C. albicans antibody positivity was found in 36.5% (19/52) of children with ASD. Anti-C. albicans antibodies in typically developing controls was (14.3%; 4/28). Overall, ASD children had a higher rate of high-positive values compared to typically developed children with an unadjusted odds ratio of 3.45 (95% confidence interval, 1.0409 to 11.4650; p = 0.041, two-tailed). (Hughes and Ashwood 2018)

The above study takes the line that Candida albicans is a "passive commensal" that "under certain conditions [...] is capable of transitioning to its pathogenic and invasive fungal form" (Hughes and Ashwood 2018). In reality, C. albicans encompasses a variety of strains, some of which live more as a commensal and others more as a pathogen: 

Here, intra-species analyses of C. albicans isolates revealed extensive variation between strains, both at the genotypic and phenotypic level. Substantial genomic differences were observed between the set of 21 clinical strains and included single nucleotide polymorphisms, inversions, copy number changes, LOH events, and whole or partial chromosomal aneuploidies.

[...] The phenotypic plasticity of this species has long been recognized, and our studies reveal the genetic differences underlying phenotypic differences are due to a variety of mechanisms, of which LOH and aneuploidy are major contributors. Furthermore, we uncover a genetic polymorphism responsible for altered phenotypic behavior, including a change in the balance between commensalism and pathogenesis. (Hirakawa et al. 2015)

Some strains of C. albicans have evolved the capacity to adhere to neural tissue:

An ex vivo adhesion assay was used to examine adhesion of Candida albicans yeast cells to brain tissue of the primate Macaca mulata. Tissues from frontal lobes and striatum (caudate, putamen, and portions of the globus pallidus) were used in the assay. Yeast cells adhered to gray matter at about six times the level of adhesion to white matter. The fungus was able to bind to different cell types within the cortex, basal ganglia, and white matter. Binding to neurons, small neurons or glia, endothelial cells, and neuropil was observed. (Denaro et al. 1995)

What's in it for the pathogen?

This is the weakest link in the argument for behavioral manipulation. How does autism benefit the pathogen? Does it help Candida spread to another host? If not, where is the benefit? People have speculated about the evolutionary advantage of autism, but only from the standpoint of the affected person. Perhaps a low dose makes one more inventive and creative (Pickard et al. 2011). Perhaps it gives rise to the "autonomous imagination" of shamans:

[…] “autonomous imagination” [is] a framework for cross-cultural interpretations of inner experience such as dreams, waking visions, trance, spirit possession and mediumship, and shamanistic and meditative states.

[…] Autonomous imagination is characterized by: a) being more freely and richly inventive than ordinary thought; b) emerging into conscious awareness in the form of vivid hallucinatory imagery which is experienced as an external reality; c) possessing a more extensive access to memory; d) exhibiting a special sensitivity to external cues and direction which enables communication to and from deeper levels of the mind, while bypassing conscious awareness, and; e) possessing a capacity to influence somatic and intrapsychic processes usually beyond conscious control (Stephen and Suryani 2000)

Shamans, through their prestige and reproductive success, may have favored a predisposition to autism in the gene pool. This hypothesis assumes that autism is mainly due to a genetic predisposition, i.e., that autism is highly heritable. In fact, heritability is "moderate": 37% for autism and 38% for autism spectrum disorder (Hallmayer et al. 2011). As with male homosexuality, it looks like something in the environment is interacting with a genetic predisposition.

If we take the pathogen's standpoint, we must ask how an autistic person might become an interesting means to spread from one host to another. One possibility is the shaman's role as a community healer. Certain healing practices involve intimate contact. In particular, a shaman's phlegm may be thought to contain the essence of his power. 

A shaman also has a magical phlegm called yachay, lodged in his stomach, which gives him the ability to blow away evil and to such out the sorcery objects (virote) that cause certain forms of illness. (Gow 1996, p. 93)

By targeting people who are likely to fill the position of community healer, a pathogen could greatly increase its opportunities for transmission. 


Parting thought

This example suggests that the evolution of behavioral manipulation can involve more than a pathogen and a host. It may also require a genetic predisposition and a cultural context that create opportunities for behavioral manipulation.


References

Denaro, F.J., J.L. Lopez-Ribot, and W.L. Chaffin. (1995). Adhesion of Candida albicans to brain tissue of Macaca mulata in an ex vivo assay. Infection and Immunity 63(9): 3438-3441.
https://iai.asm.org/content/iai/63/9/3438.full.pdf

Gow, P. (1996). River People: Shamanism and History in Western Amazonia. In Thomas, N., and C. Humphrey (eds). Shamanism, History, and the State (pp. 90-113). Ann Arbor: The University of Michigan Press. 
https://books.google.ca/books?hl=fr&lr=&id=3_inrj3puRQC&oi=fnd&pg=PA90&dq=%22River+People:+Shamanism+and+History+in+Western+Amazonia%22&ots=r2_OIZbV5M&sig=aH8LVaJwqbmFUn3FpuARh3N3UF8#v=onepage&q=%22River%20People%3A%20Shamanism%20and%20History%20in%20Western%20Amazonia%22&f=false

Hallmayer, J., S. Cleveland, A. Torres, et al. (2011). Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism. Archives of General Psychiatry 68(11): 1095-1102.
http://www.feat.org/Portals/0/Document%20Library/Medical%20Research%20Abstracts/GeneticHeritability_2011_07_04.pdf 

Hirakawa, M.P., D.A. Martinez, S. Sakthikurmar, M.Z. Anderson, A. Berlin, S. Gujja; et al. (2015). Genetic and phenotypic intra-species variation in Candida albicans. Genome Research 25: 413-425.
https://europepmc.org/articles/pmc4352881

Hughes, H.K., and P. Ashwood. (2018). Anti-Candida albicans IgG antibodies in children with autism spectrum disorders. Psychiatry 26 November
https://www.frontiersin.org/articles/10.3389/fpsyt.2018.00627/full

Pickard, C., B. Pickard, and C. Bonsall. (2011). Autistic spectrum disorder in prehistory. Cambridge Archaeological Journal 21(3): 357-364.
https://www.research.ed.ac.uk/portal/files/539348/2011_CAJ_Pickard_etal.pdf

Stephen, M. and L.K. Suryani. (2000). Shamanism, psychosis and autonomous imagination. Culture, Medicine and Psychiatry 24: 5-40.
https://link.springer.com/article/10.1023/A:1005528028869

Echoes of the Upper Paleolithic?

Among early modern humans, men faced less mate competition with increasing distance from the equator. They were proportionately fewer in number and fewer of them could afford a second wife. This was partly because hunting distances were correspondingly longer, so that more men died of hunting fatalities, and partly because longer winters made polygyny costlier. With fewer opportunities for food gathering, women were less self-reliant and depended more on men for food (Frost, 2006).

But what happened to those women who remained single? If they had no providers, wouldn’t they have died of starvation and wouldn’t these deaths have balanced out the operational sex ratio?

The short answer is that they remained with their parents and never had children. It is, above all, children who incur food-provisioning costs and make a male provider necessary. Nonetheless, it is interesting to speculate about these single women who must have been numerous among early Europeans, particularly in the continental Arctic of Ice Age Europe where opportunities for food gathering were few and far between.

If contemporary hunter-gatherers are a guide, such women become secondary caregivers by caring for younger siblings or aging parents. This spinsterhood is temporary, unless the woman suffers from a serious disability. How, then, would a hunter-gatherer society cope with large numbers of women who remain single? I addressed this question in my 1994 Human Evolution article.

Patterns of behaviour become stereotyped over time, with the result that their ritualized vestiges can persist much longer than the conditions that created them. A surplus of unattached females should be associated with a pattern of specialization in communal rather than family-oriented niches, e.g. shamanism, maintenance of base-camp dwellings, and tending of communal fires. Another pattern should be taboos that would have come to define this caste of unmarried women, e.g. virginity as a mark of caste membership, immunity from harm for fear of their shamanistic power.

Shamanism is strongly linked in early European traditions to women, especially virgins. This linkage is weaker in Siberian cultures, where female shamans predominate but are nonetheless married, and virtually unknown to the native peoples of North America, among whom most shamans are married men (Czaplicka, 1969: 243-255; Saladin d'Anglure, 1988; Hallowell, 1971: 19-22). The oldest sources from Greco-Roman, Germanic, and Slavic culture areas show an overwhelming preponderance of women among seers, witches, sibyls, oracles, and soothsayers (Baroja 1964: 24-57). Gimbutas (1982) and Dexter (1985) have argued that virgin females in early Europe were seen as "storehouses" of fertile energy and thereby possessed of extraordinary power. Thus, at the dawn of the Christian era the geographer Pomponius Mela mentioned nine virgin priestesses on an island off Brittany who knew the future and gave oracular responses to sailors who consulted them (Chadwick, 1966: 79). The first-century historian Cornelius Tacitus described a virgin prophetess among the Bructeri in present-day Germany, saying that this tribe "regards many women as endowed with prophetic powers and, as the superstition grows, attributes divinity to them" (Tacitus Histories 4:61). A similar caste of prophetesses, called dryades, existed among the Gauls (Chadwick, 1966: 80-81).

Single women also figured in what appear to be ritualized communal activities. The first-century geographer Strabo described a community of women who inhabited an island at the mouth of the Loire where "no man sets foot." (Geography 4.4.6) A sacred rite required them to unroof the temple and roof it again before sunset, a rite which Lefèvre (1900: 93) interpreted as recalling an age when women daily removed their hut's thatched roof to air the smoke-filled interior.

Another pattern links female virginity to the tending of communal fires. In both Roman and Greek mythology a virgin goddess, Vesta or Hestia, guards the communal hearth. The cult of Vesta required that the sacred fire of Rome be tended by a caste of virgin women — the Vestals. There is general agreement that this cult constituted an archaic element of Roman religion; the word Vesta, itself an archaism, appears to have come down unchanged from proto-Indo-European (6,000 B.P.), suggesting ritualization at an early date (Dumézil, 1970: 311-324). The idea that a celibate female must guard the hearth still survives in European folklore, the most familiar example being Cinderella — an unmarried woman whose name came from her having to sleep by the cinders of the fireplace.

Is there direct evidence of ‘excess’ women among Ice Age Europeans? We have a snapshot of one extended family from the Magdalenian period. The Maszycka Cave in Poland has yielded the remains of 3 men, 5 women and 8 children, all apparently from the same family and all apparently dying the same sudden death (Kozlowski & Sachse-Kozlowska, 1995).

References

Baroja, J.C. (1964). The World of Witches, trans. by N. Glendinning, Weidenfeld and Nicolson.

Chadwick, N.K. (1966). The Druids, University of Wales Press.

Czaplicka, M.A. (1969). Aboriginal Siberia. A Study in Social Anthropology, Clarendon.

Dexter, M.R. (1985). Indo-European reflection of virginity and autonomy. Mankind Quarterly, 26, 57-74.

Dumézil, G. (1970). Archaic Roman Religion, University of Chicago Press.

Frost, P. (2006). European hair and eye color - A case of frequency-dependent sexual selection? Evolution and Human Behavior, 27, 85-103

Frost, P. (1994). Geographic distribution of human skin colour: A selective compromise between natural selection and sexual selection? Human Evolution, 9, 141-153.

Gimbutas, M.A. (1982). The Goddesses and Gods of Old Europe, 6,500-3,500 BC, myths and cult images. University of California.

Hallowell, A.I. (1971). The Role of Conjuring in Saulteaux Society, Publications of the Philadelphia Anthropological Society, Vol. 2, Octagon.

Kozlowski, S.K., & Sachse‑Kozlowska, E. (1995). Magdalenian family from the Maszycka Cave. Jahrbuch der Römisch Germanischen Zentral Museums Mainz, 40, 115‑205. Jahrgang 1993, Mainz.

Lefèvre, A. (1900). Les Gaulois - origines et croyances, Librairie C. Reinwald.

Saladin d'Anglure, B. (1988). Penser le "féminin" chamanique. Recherches amérindiennes au Québec, 18(2-3), 19-50.

Strabo. (1923). The Geography of Strabo, Loeb Classical Library, William Heinemann.

Tacitus. (1969). The Histories, Loeb Classical Library, William Heinemann.