DHEA and Increased Homocysteine in Schizophrenia and Other Mental Disorders and Declines

Copyright 2004, James Michael Howard, Fayetteville, Arkansas, U.S.A.

It is my hypothesis that schizophrenia results from low dehydroepiandrosterone (DHEA) in utero / neonatal. This results in reduced growth and development of the brain. Subsequently, the hormones cortisol (stress) and testosterone in both sexes (puberty), alone but most likely in combination, combine to reduce DHEA at the time when DHEA naturally begins to decline around age twenty. This then exposes, and further damages the reduced development of the brain of early life, and causes the symptoms of schizophrenia to begin and usually worsen with time. Low DHEA is a characteristic of schizophrenia.

Applebaum, et al., (J Psychiatr Res. 2004 Jul-Aug;38(4):413-6) report that "Homocysteine levels were markedly increased in this population of newly admitted schizophrenic patients, especially in young males." It is important to my hypothesis regarding low DHEA in schizophrenia, and other mental disorders and declines, that Bednarek-Tupilowska and Tupilowski reported that "Individual data showed that dehydroepiandrosterone probably lowers Hcy [homocysteine] level." (Postepy Hig Med Dosw (online) 2004; 58: 381-9. It should also be noted that cortisol and testosterone both raise homocysteine levels, also supporting my hypothesis.

Increased homocysteine is also found in many other disorders and diseases. I suggest reduced DHEA may be the root cause of these as well.

J.M. Howard wrote: "It is my hypothesis that schizophrenia results from low dehydroepiandrosterone (DHEA) in utero / neonatal."

Interesting. How does this notion reconcile low DHEA levels in twins discordant for schizophrenia? If low DHEA levels are found in utero, wouldn't both twins be affected?

Indeed, homocysteine has been found in many disorders and diseases. Do you think, reduced DHEA would also explain biopolar disorder?

Bettye said:

J.M. Howard wrote: "It is my hypothesis that schizophrenia results from low dehydroepiandrosterone (DHEA) in utero / neonatal." Interesting. How does this notion reconcile low DHEA levels in twins discordant for schizophrenia? If low DHEA levels are found in utero, wouldn't both twins be affected? Indeed, homocysteine has been found in many disorders and diseases. Do you think, reduced DHEA would also explain biopolar disorder?

DHEA for twins would be lower for both. Therefore, I would expect to find consequences of this effect. In fact, concordant and discordant twins with schizophrenia both show reduced brain volume. I suggest this would be predicted by sharing of DHEA by twins (Biol Psychiatry. 2004 Sep 15;56(6):454-61). However, there are differences in volumes within the brains of those discordant, suggesting environmental influences, as the authors of the citation suggest. It is my hypothesis that the in utero effects of low DHEA produce a brain vulnerable to schizophrenia because of low maternal DHEA. Once born, an individual may or may not produce "normal" DHEA. Normal DHEA would protect from the reductions in DHEA in life caused by stressful events (environmental influences) and testosterone. However, since most schizophrenics do produce low DHEA, these events may trigger a decline in their already reduced brains which produces the symptoms of schizophrenia.

I have thought about bipolar disorder and suspect that DHEA may be involved. However, this one is difficult to put together. Homocysteine levels have been found to be elevated in bipolar. High DHEA are connected with bipolar and lithium has been found to reduce DHEA in rat brains. The connection may occur when depression occurs in bipolar. It is my hypothesis from 1985 that low DHEA results in depression and this has since been supported.

Does anyone know about the genetics of DHEA (e.g. parent passes down low production of DHEA)? Could the genetics of it be correlated with the genetics of schizophrenia?

It's interesting that biopolar patients show elevated DHEA and that lithium reduces its level. That suggests (rather simply) that elevated DHEA is correlated with mania, which indirectly supports your hypothesis that low DHEA results in depression. Have there been any studies correlating homocysteine or DHEA levels with patients diagnosed with clinical depression?