Sunday, November 3, 2019

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.


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.

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.

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. 

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.

Hughes, H.K., and P. Ashwood. (2018). Anti-Candida albicans IgG antibodies in children with autism spectrum disorders. Psychiatry 26 November

Pickard, C., B. Pickard, and C. Bonsall. (2011). Autistic spectrum disorder in prehistory. Cambridge Archaeological Journal 21(3): 357-364.

Stephen, M. and L.K. Suryani. (2000). Shamanism, psychosis and autonomous imagination. Culture, Medicine and Psychiatry 24: 5-40.