Saturday, December 8, 2007

What are some genetic causes of psychosis?

In our bodies, we have two types of DNA (genetic material) that get passed down to our children in very different ways.

Nuclear DNA: Nuclear deoxyribonucleic acid (referred to as nDNA or simply, DNA) is what we commonly think of when we think of “genetics” and genes. It is the DNA in the nucleus of the cell. It is the DNA we learn extensively about in biology class when we learn about “meiosis” and the forming of “gametes”—the sperm and eggs that merge to create our precious children.

Mitochondrial DNA: The other type of DNA is located in little organelles in the cell cytoplasm called the mitochondria. It gets referred to as mtDNA.

The mitochondria are the “power-houses” of the cells. We inherit a set of mitochondria from the mother’s egg cell. Which of the mother’s mitochondria that ends up in the egg cell is random. When the egg starts splitting to form the ball of cells which will become the baby, some cells may get more of one type of mitochondria than another type. The distribution may not be exactly the same throughout the resulting body.

Disorders inherited from mitochondrial DNA can be much more difficult to determine. To complicate matters, nuclear DNA can affect the functioning of mitochondria, so some inherited diseases of the mitochondria can actually arise in the nuclear DNA.

Here is a partial list of some of the genetically transmitted medical disorders that doctors say can have psychotic symptoms[1]. These are not labeled “psychotic disorders”:

Turner’s syndrome (XO karyotype)
Wilson’s disease
Velocardiofacial syndrome (VCFS--22q11 deletion, also known as Shprintzen & DiGeorge syndromes)
congenital adrenal hyperplasia (*)
erythropoietic protoporphyria
Fabry’s disease
familial basal ganglia calcification
G6PD deficiency
Gaucher’s disease
Huntington’s chorea
ichthyosis vulgaris
Kartagener’s syndrome
Klinefelter’s syndrome (karyotype 47,XXY),
metachromatic leukodystrophy,
Niemann-Pick disease,
acute intermittent porphyria.

Here are some links to information about inherited mitochondrial disorders causing psychosis. Sometimes, the only symptoms manifesting of a problem in mitochondria is in the brain, and may get diagnosed as “schizophrenia”.

Mitochondrial myopathies
Leigh syndrome, subacute sclerosing encephalopathy
Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)
Myoneurogenic gastrointestinal encephalopathy (MNGIE)

In addition, it is suspected that the stress of severe symptoms of fear, emotional dysregulation, anxiety, paranoia, delusions, and psychosis resulting from the child’s neurobiological brain disorder can cause severe oxidative stress and dysfunction of the mitochondria without the presence of an actual inherited mitochondrial disorder. It is possible, however, that there is a genetic predisposition to this oxidative stress.

Sadly, as we now discover more genetic causes of psychosis that were previously called "schizophrenia", rather than creating new labels for them, we apparently are still calling them "schizophrenia".

References and Notes

[1] Is Schizophrenia a Psychotic Disorder?  - Dr. Henry Nasrallah

[*] CAH can cause anxiety and depression which can contribute to psychosis in predisposed individuals. Although psychosis is listed as a symptom by some doctors, a direct link has not been definitively proven. It is possibly just a secondary, contributing factor.

Further Reading:
Genetics and Epigenetics:

Property of
Last Updated:
16 November 2011


KellyCARES said...

Can you please give the citation for congenital adrenal hyperplasia causing psychosis? I thought there have been no studies that have pinpointed it as a cause.

Jeanie said...

Thanks, I added the list source.

For those who may not know what we are talking about, congenital adrenal hyperplasia, also known as Adrenogenital syndrome and 21-hydroxylase deficiency, refers to a group of inherited adrenal gland disorders. People with this condition do no produce enough of the hormones cortisol and aldosterone, and produce too much of androgen.

I am also asking a friend of mine in medical school if it is being listed in her medical books as causing psychosis.

It has been explained thusly by my daughter's doctors about her own low cortisol (but from a different etiology).

The low cortisol makes a person extremely vulnerable to stressors and is involved in PTSD and possibly escalating into psychptic symptoms however brief. To make matter worse, the low cortisol can inhibit the conversion of T4 thyroid hormone to the T3 form which the body actually uses. The low T3 can also cause a person to be extremely vulnerable to stressors, cause depressive symptoms, and other major psychiatric stmptoms (including psychosis).

I suspect that the condition is being listed as having a possible symptom of psychosis in some individuals due to a secondary effect of the low cortisol, rather than the primary one. But I am not an endocrinologist.

Sometimes to look at what effect a low hormone (or elevated one) can really have, one must look at the whole cascade. I know that my brain was swimming whaen the doctors started talking about my daughter's low T4->T3 conversion possibly due to her low cortisol, possibly influenced by the low progesterone...but then there is also the low T4 and the low hormones from hypothalamic function... say what!?

The endocrine system is a complex feedback loop. The low hormones in one area can create low hormones in other areas. I suspect that's why it is being included in "the list".