Psychiatric genetics is basically a research program with no connection to treatment except for very rare high impact genetic loci.
An endophenotype refers to a characteristic that is not easily observed on the surface. Almost all mental illnesses are due to epigenetic dysregulations. The endophenotypes of psychiatric illnesses would be the sets of epigenetic marks that are associated with given mental illnesses. The variability in symptoms in given illnesses is due to variations on the basic sets of epigenetic marks associated with such illnesses.
Mental illnesses arise due to dysregulation of TET enzymes and JmnjC-domain containing .proteins with TET enzymes involved in DNA demethylation and JmnjC-domain containing proteins involved in histone demethylation. Histone acetylation which requires acetyl-coenzyme A also plays a part.
Though dysregulation of TET enzymes and JmnjC-domain proteins and dysregulation of acetyl-coenzyme A are fundamental to all mental illnesses various mental illnesses separate from each other as spatially closely associated pathways fall together. Use the pathways or lose the pathways. And as these are epigenetic dysregulations, pathways that are lost are spatially localized to various organs and/or regions of organs, for example, regions of the brain. Trying to distinguish mental illnessesby examining genes is pointless.
Trying to isolate endophenotypes so as to enhance treatments is not necessary. With basic epigenetic dysregulations addressed almost all mental illnesses. can be treated. A treatment that addresses dysregulation of TET enzymes and JmnjC-domain proteins and dysregulation of acetyl-coenzyme A could address all mental illnesses.
The thyroid may still yet have large undiscovered lands. There are many ways that individuals can feel below par.. Sadness in depressions is different than malaise, fatigue are lethargy though malaise, fatigue and lethargy are very frequently associated with depression.
Sadness in all depressions could be due to dysregulation of iodide transporters. Thyroid hormone levels can be normal while thyroid hormone homeostasis can be upset resulting in sadness though thyroid tests show patients as apparently euthyroid. In all instances of intense sadness iodide transporters could be dysregulated even intense sadness due to mourning.. A reasonable period of mourning would, of course, not call for pharmaceutical treatment.
There is an upside to this and a downside to this. Sadness is all depressions except due to mourning, could be highly pharmaceutically treatable. Sadness can pop up in almost any illness and everywhere depression as sadness pops could be due to dysregulation of iodide transporters. Sadness in all depressions could be treated by iodide from kelp, l-tyrosine and Se-methylselenocysteine. Iodide from kelp, L-tyrosine and Se-methylselenocysteine would not treat all states associated with depression only sadness. Kelp and L-tyrosine have to be taken three or four times a day. Thyroid tests must be obtained. The goal is most definitely not high thyroid hormone levels. Iodide from potassium iodide apparently reacts with too many substances. The effect of iodide from potassium iodide is not dependable. Approximately 1000 micrograms of iodide from kelp have to be taken each dosage. Iodide from kelp and L-tyrosine are taken three times a day . L-tyrosine taken without iodide is not helpful. L-tyrosine is taken on an empty stomach. Se-methylselenocysteine is supplemented. Selenium is required for thyroid hormone homeostasis. 200 micrograms of Se-methylselenocysteine is taken once a day. More Se-methylselenocysteine is not better.
The downside of this is that iodide from kelp, L-tyrosine and Se-methylselenocysteine would only treat sadness. Individuals could still feel way below par even though their intense sadness had been addressed . The SMVT besides transporting iodide also transports biotin, lipoate and pantothenic acid.. Supplemental iodide would not necessarily re-regulate the SMVT. At this point treatment becomes much more complex. Under no grounds should lipoic acid ever be supplemented as lipoate is synthesized on residues and supplemental lipoic acid would only block the SMVT. Iodide from kelp, L-tyrosine and Se-methylselenocysteine can do a lot but far from everything.
Yet the key selling point of most mineral supplements is increased absorption with increased absorption demanding that the gut be bypassed. Moreover almost all clinical studies done on humans employ inorganic forms of minerals rather than chelated organic forms of minerals. ‘Zinc gluconate human‘ turned up 560 results in Pubmed whereas ‘zinc methionine human, turned up 11 results where there were two human trials with an equivocal result in one of the trials and a positive result on a narrow measure of reduced acne in the other.
Individuals taking organic chelated mineral supplements are venturing into unknown lands and I think dangerous lands. Chelated minerals are highly absorbed but that is a bug not a feature.
The first step in the synthesis of thyroid hormones is catalyzed by thyroid peroxidasewhich requires hydrogen peroxide. Hydrogen peroxide used by thyroid peroxidase is produced by dual oxidase 1 and dual oxidase 2. Hydrogen peroxide is both required for thyroid hormone synthesis but also can be toxic to the thyroid gland. Selenium is required both for thyroid hormone synthesis and protection of the thyroid from hydrogen peroxide needed to synthesize thyroid hormones. .
600 milligrams of carbonyl iron taken at bedtime can treat a psychosis quickly. A huge difficulty is that individuals who are not psychotic can feel wretched.
200 micrograms Se-methylselenocysteine can quickly treat disorganization in schizophrenia. A difficulty here is that a whole lot is askew in schizophrenia.
Chelated minerals are not bioavailable in the gut but supplemented minerals must be bioavailable in the gut. Tests could be done on gut enzymes after chelated mineral supplementation. for example on molybdenum glycinate, compared with non-chelated mineral supplementation.
Individuals taking lithium and anticonvulsant mood stabilizers will have deficiencies in biotin, pantothenic acid and coenzyme A.
Emmanuelle Charpentier and Jennifer Doudna – awarded the Nobel Prize for work on CRISPR
CRISPRstands for clustered regularly interspersed short palidromic repeats. The key fact about CRISPR is that CRISPR makes gene editing very easy to do. CAS9, which is an enzyme that makes double stranded breaks in DNA, guided by a guide RNA can cut out undesired DNA and then insert desired DNA at any give location in the genome with the DNA strand then put back together via homologous repair. There are difficulties in off target edits with CRISPR but I will not go into that.
How helpful will CRISPR be to schizophrenia?. By and large CRISPR will be no help at all. There are a few rare high impact alleles in schizophrenia that could be edited out but in the vast majority of cases a single gene edit would not even be noticeable. Ten edits would not be noticeable. A hundred edits would hardly be noticeable. And what is more schizophrenia is associated with common alleles which presumably, as evidenced by being common, serve very useful functions.
A lot of polygenetic diseases would be as difficult to gene edit out of existence as schizophrenia would be. The same deal applies to beneficial polygenetic traits. Gene editing for beneficial polygenetic traits would demand way too much gene editing where outcomes would be highly uncertain and could very easily be disastrous . Attempting to gene edit humans genomes to eradicate polygenetic illness or to drive beneficial polygenetic traits is not only immoral but also an error.
A lot of good can be done with edits of single genetic loci. With humans CRISPR should stick to editing single loci where the edited genetic loci has a high impact on an illness or trait.. George Church doing massive edits on elephant DNA could be allowed but humans should be off limits is terms of massive gene edits.