An aside on psychiatric links from Sid Dishes

Sid has recently put these two excellent links up on her Facebook timeline. The Protons thread is slowly working its way towards probable causes of complex I failure and an awful lot of the basic mitochondrial information comes from papers on Parkinsons disease or Alzheimers disease.

It has been clear for some time that many, many mitochondrial problems, when localised in specific sets of neurons, are categorised as psychiatric illnesses without needing to have a full blown genetic mitochondrial disease at their core. Acquired mitochondrial dysfunction, most likely at complex I, might well be all you need. Have the right SNPs in genes for proteins of the ETC or assorted ion channels might allow you to be allocated schizophrenia, bipolar disorder or major depression as your pigeonhole.

Trying to treating mitochondrial psychosis by tinkering with the superficial knock on effects at the neurotransmitter level will be of limited effectiveness. Altering bioenergetics using an NAD+ precursor or by inducing ketosis might be far more logical approaches.

Enjoy:

The psychiatric presentation of mitochondrial disorders in adults

Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra.

The second paper is a rather broad brushed picture of evolution, society and NADH. Gross NAD deficiency with adequate calories (pellagra) will mean that there is almost no time for NAD+ to exist before being reconverted to NADH. The high NADH/NAD+ ratio will particularly favour excess superoxide generation at complex I if there is any reverse electron flow from the CoQ couple. It's a pity this paper does't have mtG3Pdh in its diagram of the ETC. An interesting read even if it's full of concepts which the Hyperlipid perspective might question or might invert the causality there-of.

EDIT: I found this one myself and nearly lost it. The perils of PubMed-ing in your lunch break at work and not emailing the link to yourself!

Neuroanatomical Pattern of Mitochondrial Complex I Pathology Varies between Schizophrenia, Bipolar Disorder and Major Depression

END EDIT



Peter