https://www.ncbi.nlm.nih.gov/pubmed/31655921

Neurogenetics. 2019 Oct 26. doi: 10.1007/s10048-019-00593-2. [Epub ahead of print]

Infectious stress triggers a POLG-related mitochondrial disease.

Abstract

A 3-year-old girl presented with severe epilepsy in the context of Borrelia infection. After ceftriaxone/lidocaine administration, she showed secondarily generalized focal crises that led to neurological and motor sequelae. Genetic studies identified in the patient two heterozygous POLG mutations (c.2591A>G; p.Asn864Ser and c.3649G>C; p.Ala1217Pro). Through analysis of POLG activity in cultured fibroblasts, we confirmed that the mutations altered the mtDNA turnover. Moreover, patient fibroblasts were more sensitive than controls in the presence of a mitochondrial replication-affecting drug, the antiretroviral azidothymidine. To test if ceftriaxone treatment could worsen the deleterious effect of the patient mutations, toxicity assays were performed. Cell toxicity, without direct effect on mitochondrial respiratory function, was detected at different antibiotic concentrations.

The clinical outcome, together with the different in vitro sensitivity to ceftriaxone among patient and control cells, suggested that the mitochondrial disease symptoms were hastened by the infection and were possibly worsened by the pharmacological treatment.

This study underscores the benefit of early genetic diagnosis of the patients with mitochondrial diseases, since they may be a target group of patients especially vulnerable to environmental factors.

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**Comment**

Great work hailing from Spain demonstrating that some patients have a genetic predisposition setting them up for treatment failure. This is not a “21 days of doxycycline” treatment and the sooner mainstream medicine wakes up from its coma the better!  Until it does, patients will not improve.

I found I had a genetic predisposition which caused disulfiram psychosis:  https://madisonarealymesupportgroup.com/2019/10/15/disulfiram-psychosis-update/

https://madisonarealymesupportgroup.com/2019/10/27/disulfiram-psychosis-update-2/

Reports are coming in that I’m not alone.  For research regarding this:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290718/

Abstract

Disulfiram is the commonly prescribed drug for the treatment of alcohol dependence. It’s major metabolite (diethyldithiocarbamate) is an inhibitor of dopamine-betahydroxylase, an enzyme that catalyzes the metabolism of dopamine to norepinephrine resulting in psychosis. We recommend that disulfiram should be used at the lowest effective dose, possibly 250 mg daily and caution should be taken while prescribing disulfiram for patients with personal and familial antecedents of psychosis.…..Disulfiram-related psychiatric complications are reported to be more prevalent in eastern countries,3) which suggests that genetic factors may play a role in disulfiram induced psychosis.
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In this paper, a hypothesis of vulnerability to disulfiram psychosis is proposed, based on the current lines of evidence for the biological mechanisms involved in the psychoses.

Disulfiram Is a DA Agonist

Disulfiram is an inhibitor of dopamine-beta- hydroxylase (DBH), an enzyme that catalyzes the metabolism of DA to norepinephrine (NE).3 By inhibiting the metabolic pathway from DA to NE in the central nervous system, disulfiram results in an increase of DA concentrations. Therefore, disulfiram is a DA agonist, and is likely to exacerbate preexisting or latent psychosis, similar to amphetamine, methylphenidate and L-dopa.

DA and Affective Psychosis

Increased brain DA is highly correlated with psychomotor activity in animals, and L-dopa has been shown to produce episodes of hypo mania and mania in most patients with bipolar affective psychosis.4 It is possible, therefore, that disulfiram can uncover a preexisting or latent hypomania or mania.