The American Heart Association alters the natural history of bipolar disorder

l Individuals with bipolar disorder

Mania and periods of hypomania could have become rarer with the recommendations of the American Heart Association to avoid long chain saturated fats. With the decrease in intakes of long-chain saturated fats periods of depression in bipolar disorder lengthen. Individuals with bipolar disorder are now mainly depressed or rapidly cycling. What was bipolar disorder historically is now no longer bipolar disorder. .

Opioids can result in euphoria so opioid antagonists would be perfect for individuals with schizophrenia

l

Samidorphan is an opioid antagonist. Samidorphan supposedly reduces weight gain that very frequently occurs with olanzapine. ALKERMES INC, a pharmaceutical corporation, concluded that individuals with schizophrenia could benefit from less than normal opioid agonism, which fits right in with the history of the treatment of schizophrenia. Some terrible treatment is somehow or other a boon to individuals with schizophrenia. Olanzapine/samidorphan, with olanzapine being the antipsychotic and samidorphan being the opioid antagonist, combines two pleasure killing drugs in one pill so, of course, olanzapine/samidorphan is a treatment advance for individuals with schizophrenia. Metabolic parameters did not vary between olanzapine and olanzapine/samidorphan and individuals on olanzapine/samidorphan still gain weight. Also a meta-analysis indicates that olanzapine/samidorphan is not effective in reducing weight gain due to olanzapine. LYBALVI, an olanzapine/samidorphan combination, was recently approved by the FDA for the treatment of schizophrenia and bipolar 1 disorder.

Cortical thickness and antipsychotics

Cortical thickness is negatively correlated with normalized antipsychotic dosage with first generation antipsychotics having an especially negative effect on cortical thickness. The negative effect of antipsychotics on cortical thickness provides additional grounds for using antipsychotics in the lowest feasible dosage. Individuals with schizophrenia not on antipsychotics have decreased cortical thinning compared to individuals with schizophrenia on antipsychotics.. Cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. See also Antipsychotic Effects on Cortical Morphology in Schizophrenia and Bipolar Disorders. Antipsychotics are flat out toxic to brains.

Schizophrenia, anosognosia and Se-methylselenocysteine

Lack of insight or lack of awareness of illness in schizophrenia is termed anosognosia with some 30% of individuals with schizophrenia having anosognosia. The cardinal feature of anosognosiais not elaborate delusions rather the cardinal feature of anosognosia is confusion and disorganization. Individuals with agonosgnosia are having terrible cognitive difficulties. Se-methylselenocysteine treats cognitive symptoms of schizophrenia. Supplemental Se-methylselenocysteine could be a treatment for anosognosia.

Patients might not be responsive to treatment for anosognosia with Se-methylselenocysteine given patients are intensely sad. With the SMVT dysregulated, which transports biotin, needed for synthesis of saturated fatty acids, fatty acids are not being synthesized. 15 grams of cococa butter must be supplemented three time a day.

Patients on Se-methylselenocysteine and cocoa butter could have ahedonia but there would be an awareness of illnesses. More organized delusions though with an awareness of illness could be a feature of the treatment. I hold more can be done to treat schizophrenia, however, Se-methylselenocysteine and cocoa butter would be a treatment for agonosgnosia…Individuals with schizophrenia could benefit greatly from 600 mg of iron from iron carbonyl taken away from other supplements, food and drinks except water.

An exclusive focus on absorption of minerals is at odds with the gut being a key to various illnesses

The gut has become a primary focus of a lot of research on various illnesses. The gut has become a focus in research on major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder, autism, anxiety, Parkinson’s disease, Alzheimer’s disease, osteoporosis, amyotrophic lateral sclerosis etc.

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.

Biohack mental illness now!

l CRISPR DIY kit not required

A lot of biohacking does not appear to be safe. For example, trying to alter at home one’s genetic makeup via CRISPR seems beyond unsafe.

A lot of biohacking is undertaken to achieve increased longevity. Biohacking for increase longevity requires that one wait around for decades to see the results. One has to wait 30 or 40 years to see whether one selected a right mix of supplements and then in all probability if one lives to a healthy 100 years of age one would not know exactly which supplements were the key supplements. Knowledge as to what increases longevity would still be lacking. One could be interviewed with questions asked as to how longevity was achieved and a laundry list of supplements would then be detailed. Someone listening to the interview could say, ‘I will eat 3 strips of bacon every morning. The other guy eats three strips of bacon every morning and is an alert, healthy 102 year old.’

A lot of specialty nootropics taken for cognitive enhancement have unclear effects and have not been widely tested in clinical trials . Moreover most nootropics are likely manufactured in China which does not have a reputation for tight controls on drug manufacture. What is more there would be a huge mainstream market for nootropics given noontropics worked. Individuals with mental illnesses very frequently could use some cognitive enhancement but nootropics are not being prescribed. After decades of use and study use of nootropics appears to be a very sketchy practice.

The appeal now of becoming part cyborg is 98% aesthetic. Becoming part cyborg now does not result in cognitive enhancements or health enhancements.

Biohacking mental illness

I hold that a lot of mental illness can be biohacked now, this week. 600 milligrams of carbonyl iron taken once a day at bedtime away from other supplements, food and drinks except water can treat psychosis. Iron interacts with lots of substances, coffee and tea being two examples. The point of taking the carbonyl iron at bedtime is to take the iron away from substances that can interfere with iron metabolism in the gut. The last cup of coffee or cup of tea of the day is drunk at least 6 or 7 hours before carbonyl iron is taken. 200 micrograms of Se-methylselenocysteine taken once a day in the morning. can treat disorganization. Cocoa butter. taken three times a day away from iron is very helpful. Difficulties in the transport of biotin could lead to difficulties in the synthesis of saturated fatty acids, Difficulties in synthesis of saturated fatty acids could be addressed by supplementation with cocoa butter. MCT oil and olive oil do not work.

Cons

I hold that iron-sulfur proteins are dysregulated in schizophrenia and that 600 milligrams of carbonyl iron taken once a day at bedtime can address the psychosis of schizophrenia. There is no direct clinical evidence that iron-sulfur proteins are dysregulated in schizophrenia. Given iron-sulfur proteins were dysregulated in schizophrenia this would cause major difficulties where psychosis could be one such difficulty.

There is no clinical evidence Se-methylselenocysteine effectively treats cognitive symptoms of schizophrenia.

Pros

Dirt simple and very quick. Very safe for at least a week. If the treatment has not worked at the end of week the treatment would be stopped. If the treatment is effective then safety of the supplements can be studied further and necessary tests obtained.

A lot of research I have cited cited on the website and in papers points to iron-sulfur cluster formation and selenoprotein metabolism being dysregulated in various neurological illnesses. Dysregulation of the SMVT which has been repeatedly addressed in this blog could result in dysregulation of saturated fatty acid synthesis which could certainly result in depressive illnesses.

There could a difficulty in synthesis of saturated fatty acids due to biotin deficiencies which supplementation with cocoa butter.could address. Difficulties in the transport of biotin could lead to difficulties in the synthesis of saturated fatty acids.

Not dangerous for at least a week. Would not be taken longer than a week if not effective.

What have I said that is straightforwardly testable?

600 milligrams of carbonyl iron taken at bedtime can treat a psychosis quickly. The carbonyl iron must be taken away from food, drinks except water and other supplements.200 micrograms Se-methylselenocysteine can quickly treat disorganization in schizophrenia.

600 milligrams of carbonyl iron taken at bedtime and 200 micrograms Se-methylselenocysteine can end treatment resistant schizophrenia.A huge difficulty is that individuals who are not psychotic can feel wretched.

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 with molybdenum glycinate, compared to sodium molybdate..

Individuals taking lithium and anticonvulsant mood stabilizers will have deficiencies in biotin, pantothenic acid, coenzyme A and protein bound iodide. .

CRISPR and schizophrenia

Emmanuelle Charpentier and Jennifer Doudna – awarded the Nobel Prize for work on CRISPR

CRISPR stands 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.

Serendipity and drug discovery

Frequently scientists talk about the serendipitous finding that leads to important discoveries. In psychiatry serendipitous drug discoveries, however, may not advance understanding of psychiatric illnesses very much. Dopamine antagonists are useful in the treatment of schizophrenia but there has been no revolution in the understanding of schizophrenia resulting from the discovery that dopamine antagonists can partially treat schizophrenia. Lithium has uses but lithium has not revolutionized the understanding of bipolar disorder.

A lot of research seems directed at finding the hidden fact that will be the key to unraveling a disease. Researchers seem to be in search of serendipity which is not how serendipity works. Psychiatric research would better off if there was more emphasis on basic research with translational research then sticking closely to basic research. Succeeding at translational research may require that all the various factors that complicate a hypothesis be considered. The devil is the details. Possessing a sliver of truth is surer route to scientific discovery than searching for serendipity.

The basic idea that the transsulfuration pathway is dysregulated in schizophrenia is a simple idea but treatment is complicated by the fact that downstream pathways from the transsulfuration pathway have to be addressed. Treatment would be so much simpler if only lowering homocysteine levels worked or only increasing l-cysteine levels worked but neither do. There can be effective treatments for schizophrenia that address the fundamental biology of schizophrenia but there can be no simple effective treatments for schizophrenia that address the fundamental biology of schizophrenia.

Schizophrenia, toxoplasma gondii and iron-responsive protein 1

toxoplasma gondii

The Odd Ratio for schizophrenia for indivduals with IgG antibodies for toxoplasma gondii were 1.81, With toxoplasma gondii infection.there is increased activity of iron-responsive protein 1 (IRP1). Aconitase 1 is a dual function protein, When iron levels are low aconitase 1 loses an iron sulfur cluster and becomes IRP1 but when iron levels are increased IRP1 gains an iron-sulfur cluster and becomes aconitase 1. Aconitase 1 is an enzyme in the tricarboxylic acid (TCA) cycle. Increased levels of IRP1 would indicate that the TCA cycle is dysregulated which could set the set the stage for schizophrenia. See my paper Treatment-resistant schizophrenia: focus on the transsulfuration pathway. on how dysregulation of IRP1, aconitase 1 and the TCA cyle could play a part in the development of schizophrenia.