#6. Mental Illness as Communication [neuroscience, genetics]

NE   GE

Red, theory; black, fact

The effects of most deleterious mutations are compensated by negative feedback processes occurring during development in utero. However, if the population is undergoing intense Darwinian selection, many of these mutations become unmasked and therefore contribute variation for selection. (Jablonka and Lamb, 2005, The MIT Press, "Evolution in Four Dimensions")

Basic Darwinism Is So Inefficient

However, since most mutations are harmful, a purely random process for producing them, with no pre-screening, is wasteful. Raw selection alone is capable of scrubbing out a mistake that gets as far as being born, at great cost in suffering, only to have, potentially, the very same random mutation happen all over again the very next day, with nothing learnt. Repeat ad infinitum. This quarrels with the engineer in me, and I like to say that evolution is an engineer. 

Evolution of Evolution 

Nowadays, evolution itself is thought to evolve. A simple example of this is the evolution of DNA repair enzymes, which were game-changers, allowing much longer genes to be transmitted to the next generation reliably, resulting in the emergence of more complex lifeforms.

What I Would Like to See

A further improvement would be a screening, or vetting process for genetic variation. Once a bad mutation happens, you mark the offending stretch of DNA epigenetically in all the close relatives of the sufferer, to suppress further mutations there for a few thousand years, until the environment has had time to change significantly.

Obviously, you also want to oppositely mark the sites of beneficial mutations, and even turn them into recombination hotspots for a few millennia, to keep the party going. Hotspots may even arise randomly and spontaneously, as true, selectable epi-mutations. 

A Problem With Mutation Hotspots on the DNA Strand

The downside of all this is that even in an adaptive hotspot, most mutations will still be harmful, leading to the possibility of "hitchhiker" genetic diseases that cannot be efficiently selected against because they are sheltered in a hotspot. Cystic fibrosis may be such a disease, and as the hitchhiker mechanism would predict, it is caused by many different mutations, not just one. It would be a syndrome defined by the overlap of a vital structural gene and a hotspot, not by a single DNA mutation. I imagine hotspots to be much more extended along the DNA than a classic point mutation.

It is tempting to suppose that the methylation islands found on DNA are these hotspots, but the scanty evidence available so far is that methylation suppresses recombination hotspots, which are generally defined non-epigenetically, by the base-pair sequence.

Mental Illness In Evolution 

The human brain has undergone rapid, recent evolutionary expansion, presumably due to intense selection, presumably unmasking many deleterious mutations affecting brain development that were formerly silent. Since the brain is the organ of behavior, we expect almost all these mutations to indirectly affect behavior for the worse. Does that explain mental illness?

Mental illnesses are not random, but cluster into definable syndromes. My reading suggests the existence of three such syndromes: schizoid, depressive, and anxious. My theory is that each is defined by a different recombinant hot spot, as in the case of cystic fibrosis, and may even correspond to the three recently-evolved association cortices of the human brain, namely parietal, prefrontal, and temporal, respectively. 

How Mental Illness Could Be Beneficial 

The drama of mental illness would derive from a communication role in warning nearby relatives that they may be harbouring a bad hotspot, causing them to find it and cool it by wholly unconscious processes. Mental illness would then be the push-back against the hotspots driving human brain evolution, keeping them in check and deleting them as soon as they are no longer pulling their weight fitness-wise. The variations in the symptoms of mental illness would encode the information necessary to find the particular hot spot afflicting a particular family.

A Possible Mechanism

Now all we need is a communication link from brain to gonads. The sperm are produced by two rounds of meiosis and one of mitosis from the stem-like, perpetually self-renewing spermatogonia, which sit just outside the blood-testes barrier and are therefore exposed to all blood-borne hormones. These cells are known to have receptors for the hypothalamic hormone orexin A, as well as many other receptors for signalling molecules that do or could plausibly originate in the brain as does orexin A. Orexin A is lipophilic and rapidly crosses the blood-brain barrier by diffusion. Some of the other receptors are:

• retinoic acid receptor α
• glial cell-derived neurotrophic factor (GDNF) receptor
• CB2 (cannabinoid type 2) receptor
• p75 (For nerve growth factor, NGF)
• kisspeptin receptor.

PS: for brevity, I left out mention of three sub-functions necessary to the pathway: an intracellular gonadal process transducing receptor activation into germ line-heritable epigenetic changes, a process for exaggerating the effects of bad mutations into signals for purposes of interpersonal communication, and a process of decoding the communication in the brains of the recipients.

Photo by Charlotte Noelle on Unsplash