Life expectancy among persons with schizophrenia or bipolar affective disorder

Life-expectancy was 18.7 years shorter for schizophrenic men compared to men in the general population. Corresponding numbers for schizophrenic women was 16.3 years, for bipolar men 13.6 years, and for bipolar women 12.1 years,.’ With DNA demethylating mechanisms going awry in schizophrenia, due to dysregulation of TET enzymes and JumjC domain-containing proteins, all kinds of illnesses in individuals with schizophrenia can develop shortening life spans.

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

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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.

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.

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.