Tuesday, January 15, 2008

Specific Genes Inherited from Both Parents May Lead to Type of "Schizophrenia"

Some families have noticed a form of schizophrenia that runs in their particular family which seems to "skip" a generation. What that indicates is that there may be recessive genes involved in one parent's "schizophrenia". (That's what happened in my own family, but at least in the younger generation, we were able to beat that "genetic curse").

If the other parent does not have the same type of genes, the children would inherit only one copy and thus not get the "schizophrenia". They find that regardless of multiple other environmental risk factors they may have, none of them get the illness.

Notes that we are not talking about a single gene, but a whole constellation of genes, which together, still does not mean the person WILL get schizophrenia, but rather, they increase risk. Also remember, Schizophrenia is not one single illness, but rather, a label from the DSM for communication purposes (as are all the diagnoses in the DSM). The label means the person has some of a large set of possible symptoms of that label (for more on medical vs non-medical aspects of the label, see here: [1] [2] [3] [4]. And, Schizophrenia, schizoaffective, and bipolar (all considered to be on the same "spectrum") are not just genetic, but EPIGENTIC. This means environmental factors affect the functioning of the genes (see [5] ) and some of these epigentic are seen to be passed down to the developing fetus as well. In fact, some of these epigenetic changes HAPPEN en-utero.

Yet, the "schizophrenia" seems to appear among the children of some of those siblings or other family members, even though they may be exposed to less environmental risk factors than the generation before them.

The astounding research article below is about just the large array of genes involved and how THAT can raise... or LOWER.. the risk of schizophrenia. Why the RISK of schizophrenia often does NOT get passed down to the next generation. A leading schizophrenia research organization, NARSAD, may have come up with an explanation for such families -- an explanation for a subset of patients with "schizophrenia".

NARSAD has found recessively inherited genes which greatly increase the risk of a person developing a "subtype" or "variant" of "schizophrenia" when a child inherits the same copy from both parents.

Here is their press release:

Genes Inherited From Both Parents Could Trigger Schizophrenia
(Great Neck, NY -January 06, 2008) — A research team led by a 2001 NARSAD Young Investigator has identified nine genetic markers that can increase a person’s risk for schizophrenia.

In a study published in December in the Proceedings of the National Academy of Sciences, Todd Lencz, Ph.D., associate director of research at The Feinstein Institute for Medical Research in Manhasset, N.Y., and colleagues, reported evidence that schizophrenia can be inherited in a recessive manner.

A recessive trait is one that is inherited from both parents. “If a person inherits identical copies of these markers from each parent, his or her risk for schizophrenia increases substantially,” said Dr. Lencz, who was the paper’s lead author. One in every 100 people suffers from schizophrenia, a condition marked by episodes of hallucinations, delusions and disordered thinking.

The scientists developed a complex mathematical approach called whole genome homozygosity association (WGHA) that provides a new way of analyzing genetic information. It enables scientists simultaneously to look at genetic information derived from a patient’s mother and father, and identify pieces of chromosomes that are identical.

They tested genetic material from 178 patients and 144 controls. It has been the prevailing view in psychiatric genetics that there are probably dozens, if not hundreds, of genetic variations that could lead to schizophrenia, but that each gene has a small effect. It is the wrong mix of many genes, plus unknown environmental stressors, that trigger the onset of symptoms, according to the theory.

The new findings suggest another scenario, at least for a subset of patients. Dr. Lencz and his colleagues identified nine regions along the chromosomes that might play a large role in triggering the disease when two identical variants are inherited. Four of these regions contain genes that have been previously associated with schizophrenia. This can be interpreted as validation for the technique. The remaining five regions provide an additional set of newly discovered genetic risk factors.

Many of the genes located in these “high-risk” regions are involved with the structure and survival of neurons. In genetic parlance, several of the markers demonstrated high penetrance, meaning that their effect on disease risk was large. In the study, 81 percent of the schizophrenia patients had at least one of these recessive markers, compared to only 45 percent of the normal control group. Nearly half of the patients had two or more, compared to 11 percent of the controls. And while no one in the healthy group had identical chunks of chromosomes in four or more of these risk regions, subjects with more than three demonstrated a 24-fold increased risk of developing schizophrenia.

“This type of analysis could greatly improve our ability to diagnose schizophrenia and clarify specific subtypes of patients,” Dr. Lencz said. “The critical next step is confirming these results in independent datasets.”

“What is most exciting is that the study implicates new genes in schizophrenia,” said David Goldman, M.D., chief of laboratory of neurogenetics at the National Institute on Alcohol Abuse and Alcoholism. “Now, they have to trace down the genes that mediate this vulnerability.”

Here is the abstract of the actual research article:
Runs of homozygosity reveal highly penetrant recessive loci in schizophrenia.

And here is the link to the full scientific research article in PDF format:
Runs of homozygosity reveal highly penetrant recessive loci in schizophrenia. Lencz T, Lambert C, DeRosse P, Burdick KE, Morgan TV, Kane JM, Kucherlapati R, Malhotra AK Proc Natl Acad Sci U S A. 2007 Dec 11; 104(50): 19942-7

And something about the genetic overlap between Schizophrenia, Bipolar Disorder, and Depression -- also from NARSAD:
NARSAD Researchers Identify Specific Genes And Family Traits Linked To Schizophrenia, Bipolar Disorder And Depression

Genetics and Epigenetics:

Property of:      http://itsnotmental.blogspot.com/
Last Updated:  25 November 2012


P said...

So, does this mean that I will be able to go to a doctor, along with my spouse, to get tested for these genetic markers? Assuming that is possible, what preventative measures would we be able to take to reduce the problems that our child may have?

Jeanie said...

It can take years for genetic tests to become commercially available after discovery even when it is for a single gene. This one is even more complex because it is for a set of genes.

You want to know "preventative" measures to take.

It is not known exactly what these specific genes do and how they interact. The press release says the scientists do not know which, if any, environmental factors may interact to prevent or to trigger these sets of genes.

They say that these genes are "higly penetrant" which means that this is a highly genetic way to get this set of symptoms which can qualify for the diagnosis of "schizophrenia". They are looking for other genes that might get turned on or off that may help to modulate the symptoms.

Four of the 9 involved DNA regions related to largely glutaminergic function of the neurons at the place they communicate with each other, called synapses. But other areas were different.

If in the future there is a commercially available genetic test for these genes, the hope is that they will also have a better understanding of exactly what a person can do or take to lessen the effects of those genes, if not outright treat the underlying biology. It may be complex since so many genes are involved each contributing different factors to that complex biology.

In the meantime, we can only do what we are already doing to aid the general health of our children and unborn babies. The research does not say if additional therapeutic measures to help preserve (and grow) brain function, such as omega-3 fatty acids (fish oil), and protect against oxidative stress in the affected child, lower homocysteine levels during pregancy, etc, will have any effect on THIS particular highly inherited genetic problem, but aiming for such health cannot hurt.

I could list a hundred things that get listed as contributing factors for diagnoses of other known forms of "schizophrenia" from highly biological to emotional (usually combined with a pre-existing vulnerability in the biolgy). These range from prenatal viral infections to childhood exposure to dry cleaning chemicals!

But I can talk about some things to be aware of in general about children who carry some versions of genetic risk for some types of "schizophrenia", which may have no connection to this type. I don't know. After all, the finding of the genes have just taken place.

In general with other known versions, there may be associated risk of food sensitivities, diabetes, sensory issues, sleep issues, endocrine problems, learning differences and autoimmune problems. All these things need to be watched out for and treated appropriately.

In some cases of childhood-onset "schizophrenias" the child may have lower IQ, delayed speech, abnormal gait, impaired facial emotion recognition. There are so many different types. I do not personally know any of these cases - I've only read about them in the literature. Can those cases be prevented? Some babies are born the way they are in spite of everything a person does to try to have a good pregnancy.

If you are worried about your future children, I would suggest you do what I am sure you would do anyway. Your wife should get all her vaccinations before getting pregnant, be healthy, and eat a healthy diet, take appropriate vitamins, see her ob-gyn regularly, and avoid toxic chemicals.

Oh, and as for you... of course... you need to treat your wife like a princess :-)

After birth, in general, kids (and adults) with autoimmune problems, genetic problems, endocrine disorders, learning differences, etc, along with the ones with a type of "schizophrenia" seem to be more vulnerable to stress from their pain, sensory overload, sleep issues, physical injury, emotional overload, etc.

So, as with any child, care needs to be taken to help the child deal with their own biology, such as any sensory processing issues, to lessen the impact (stress) of those issues.

Protecting the child's body and brain with good nutrition that is appropriate to that child's biology is important. An example is a young child with migraines who may be reacting to allergens, foods, or may need supplements (such as CoQ-10).

Omega-3 fatty acids (fish oil) helps reduce inflammatory response which seems to be associated with some types of "schizophrenia", and also helps protect and regrow brain cells.

Sleep issues are also extremely important to address as that alone can hugely stress a person's body and brain.

However, these are all generalities. The authors said nothing about how to prevent or redice problems if the child actually is homozygous for this particular set of recessive genes. They cannot know if they interact with viral infections or some environmental toxin, or even with other proteins, mitochondria... or... whatever in the body.

The hope they expressed is that some day they will know exactly what to do when the person does have double copies of these genes.

The hope that I see in this research is that if one parent does not have this form of schizophrenia in their family, even if the other parent has this form, the offspring are unlikely to have the double copies, so will not be ill. (Note that the press release did not describe the form - mostly positive symptoms? Mostly negative symptoms? Catatonia? Disorganized? Paranoid? etc).

It will be interesting to see what comes out of this research down the road. For now, it has no practical value for loving parents today, except to give a potential explanation for how some types of "schizophrenia" can be inherited, how it can affect none of the children of parents with it, yet show up in the grandchildren if both parents are carriers.

Herb said...

One of beauties of using a nutritional approach to both therapeutic and preventative scenarios is how innocuous it may be. It is very rare indeed that supplementing with nutrients that the normal body uses and needs will cause harm. I, personally, would encourage supplementation, with omega 3, CoQ10 and similar nutrients if there is the slightest question. I offer as an example of the case of cod liver oil. Before the present day when Vitamin D is added to milk, autism and ADHD was almost unknown, possibly because mothers ran after their children to gve them cod liver oil which was a good source of Vitamin D to prevent rickets. The fact is that it is also a fairly good source of Omega 3s which disappeared from the diets of children when Vitamin D fortification became ubiquitous.

I would encourage Philip to begin supplementation early and even if not needed for a specific morbidity, it can't hurt and may contribute to general good health of his children. Supplemenation should be age appropriate. It is possible that a preventative dose may be too small to be an effective therapeutic dose but it can be adjusted later should a pathology appear.