A biologically valid genetic risk factor

Researchers identify new genetic risk factor for severe psychiatric illness. November 19th, 2013.

Excerpt: ” This gene is critical to neurodevelopmental processes such as axon formation and synaptic function. These findings shed new light on the genetic architecture and potential therapeutic targets for the treatment of psychiatric disease.”

This is an open access article: Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder

Concluding paragraph (with my emphasis):

“Consistency of results across both schizophrenia and bipolar disorder support a growing body of evidence that current diagnostic boundaries in psychiatric nosology are not biologically valid5, 8. [That fact has been addressed by the NIMH, ASAM, and IOM.] Although modifier genes influencing specific clinical features of the phenotype may be identified by future research, NDST3 variation appears to predispose to severe psychiatric disease of varying presentations.”

My comment: That is a scholarly way to tell some psychiatrists: “You missed manifestations of one single-nucleotide polymorphism (SNP) in at least two mental disorders!” Genome-wide significance results from the change in one base pair. There is no mention of “mutation” in the news article. Instead, as we can read in the journal article abstract: “Heparan sulphate binding is critical to neurite outgrowth, axon formation and synaptic processes thought to be aberrant in these disorders.” In my opinion, that is a subtle way to tell some psychiatrists: “The physics and chemistry of molecular bonds must be considered in the context of developmental disorders of the brain and behavior.”

I have not been so subtle. Indeed, I am demanding that all psychiatrists forget what they were taught to believe about mutations and learn to consider how olfactory/pheromonal input associated with food odors and social odors causes the epigenetic ‘landscape’ to become the physical landscape of DNA in the organized genome of species from microbes to man. My demands are not scholarly, no matter how many scholarly facts are included. On the other hand, I have not been treated like a scholar who has published a series of peer-reviewed works should be treated. With the exception of two awards for publishing (one in neuroscience and one in social science), I have been largely ignored.

Moving forward, given what is currently known about molecular epigenetics, there are Laws to be considered in nosology. For example, the Second Law of Thermodynamics appears to be at least temporarily defied in the context of increasing organismal complexity in species from microbes to man. That’s probably why physics is now being extracted from the biophysics of adaptations. Now, organismal complexity “just happens.”

However, the increased complexity of molecular bonds, which are required for amino acid biosynthesis,  suggests that we can look at achiral glycine and the addition of the methyl group, which makes it alanine, and the addition of the methyl group, which makes valine from alanine as examples of missing entropy. Entropy remains missing from the ecological, social, neurogenic, and socio-cognitive niche construction of organismal complexity associated with amino acid substitutions in species from microbes to man. It may reenter the continuum of evolution at some point in the future, nonetheless.

In the meantime, every instance of niche construction appears to be nutrient-dependent, because organisms that lack sufficient nutrients do not survive. Presumably, nutrient-uptake alters the thermodynamics of intercellular signaling that leads to alternative splicings via  SNPs that link the epigenetic “landscape” to the physical landscape of DNA.

In my model, the metabolism of nutrients to species-specific pheromones, which control the physiology of reproduction, links the increased organismal complexity of molecular bonds required for amino acid biosynthesis and degradation from SNPs to amino acids substitutions and species diversity. The results from this study support my model of what may happen to individuals who mature to become capable of reproduction. They may be genetically predisposed to be less reproductively fit by the change in one base pair that alters the entirety of intercellular thermodynamics and the development of the brain and behavior, which is controlled by nutrient-dependent organism-level thermoregulation. There’s a model for that. Also, please consider this one Explaining Organismal Complexity with Non-Coding DNA !

Author: James Kohl

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