Genetic clash doubles schizophrenia risk

November 20, 2002

UCLA scientists have discovered that infants possessing a cell protein called Rhesus (Rh) factor that their mothers lack are twice as likely to develop schizophrenia in young adulthood. Reported in the December issue of the peer-reviewed American Journal of Human Genetics, the study suggests that the gene that codes for Rh factor is to blame for the higher risk.

"Previous studies reported a link between mothers and infants who are Rh-incompatible and a higher rate of schizophrenia in the children later in life," said Dr. Christina Palmer, a research scientist at the UCLA Neuropsychiatric Institute. "Our research is the first to take a genetic approach to examining this increased risk."

Rh factor is a protein that sits on the surface of each red blood cell. A person is Rh-positive when Rh factor is present and Rh-negative when Rh factor is not. The gene that codes for the Rh protein is called Rhesus D factor (RHD).

When a pregnant woman is Rh-negative and her fetus is Rh-positive, her immune system can attack the child's red blood cells. This deprives the brain of oxygen and can cause jaundice.

"In heavy doses, oxygen deprivation and jaundice can cause serious brain damage," said Palmer, an assistant professor-in-residence of psychiatry and biobehavioral sciences. "Even more subtle consequences may set the stage for abnormal brain development and schizophrenia down the road."

In 1970 a prophylactic injection became available for Rh-negative pregnant women whose Rh factors did not match their fetuses'. Now widely used, the drug prevents women's immune systems from destroying their babies' red blood cells.

Still, a large number of Rh-incompatible children living today were born before prophylaxis was available. The UCLA team decided to conduct the first gene-based study of whether Rh incompatibility increased these children's susceptibility to schizophrenia. Prior research on this topic had been limited to birth records. "Many studies have shown that mothers of children who develop schizophrenia experience a higher rate of fetal distress and obstetric complications," Palmer said. "We hypothesized that stressors produced by Rh incompatibility in the prenatal environment -- such as oxygen deficiency to the brain -- could predispose a child for schizophrenia later in life."

To test their theory, the UCLA team collaborated with Dr. Leena Peltonen, UCLA professor of human genetics. She mapped out the genetic make-up of 181 Finnish families in which at least one family member had been diagnosed with schizophrenia. Except for three cases, all of the children in the sample were born before the introduction of prophylaxis in 1970.

Dr. Janet Sinsheimer, UCLA associate professor of human genetics and biomathematics, created a new statistical test to determine if maternal-fetal Rh incompatibility increased the likelihood of schizophrenia. UCLA colleagues Palmer, Sonia Minassian and J. Arthur Woodward used the test to scrutinize the chromosomal location of RHD and analyzed the gene's data from the Finnish subjects' DNA.

Palmer and her colleagues discovered that when a mother is Rh-negative and her fetus is Rh-positive, the child is more than twice as likely to develop schizophrenia than infants born from different maternal-fetal Rh combinations.

"We found evidence that the Rh-positive children of Rh-negative mothers possess more than double the risk for developing schizophrenia later in life," Palmer said. "This suggests that the RHD gene is a risk factor for this mental disorder."

"The next important step will be to look at Rh incompatibility in people born after 1970 to test whether prophylaxis has reduced their risk of schizophrenia."

A board-certified genetic counselor, Palmer emphasizes that the UCLA findings should not panic mothers who don't share Rh compatibility with their children. "A two-fold increase is no cause for alarm," she said. "Schizophrenia is a complex disorder that likely stems from a combination of several genetic and environmental factors. It is doubtful that Rh incompatibility alone causes the disorder."

She encouraged Rh-negative women to take advantage of Rh-incompatibility prophylaxis, receive good prenatal care and review their family histories for schizophrenia.

Schizophrenia is a disabling brain disease that afflicts 1 percent of the worldwide population and more than 2 million Americans. Palmer estimates that Rh incompatibility accounts for about 4 percent of these cases. People with schizophrenia may suffer from hallucinations, delusions, disordered thinking and loss of emotional affect. Medication can treat certain symptoms, but less than one in five people completely recovers from the disorder.
-end-
The National Institute of Mental Health funded the UCLA study. In addition to the UCLA team, Palmer's co-authors included Joni Turunen, Tiina Paunio and Jouko Lonnqvist.

The UCLA Neuropsychiatric Institute is an interdisciplinary research and educational institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders.

University of California - Los Angeles

Related Schizophrenia Articles from Brightsurf:

Schizophrenia: When the thalamus misleads the ear
Scientists at the University of Geneva (UNIGE) and the Synapsy National Centre of Competence in Research (NCCR) have succeeded in linking the onset of auditory hallucinations - one of the most common symptoms of schizophrenia - with the abnormal development of certain substructures of a region deep in the brain called the thalamus.

Unlocking schizophrenia
New research, led by Prof. LIU Bing and Prof. JIANG Tianzi from the Institute of Automation of the Chinese Academy of Sciences and their collaborators have recently developed a novel imaging marker that may help in the personalized medicine of psychiatric disorders.

Researchers discover second type of schizophrenia
In a study of more than 300 patients from three continents, over one third had brains that looked similar to healthy people.

New clues into the genetic origins of schizophrenia
The first genetic analysis of schizophrenia in an ancestral African population, the South African Xhosa, appears in the Jan.

Dietary supplement may help with schizophrenia
A dietary supplement, sarcosine, may help with schizophrenia as part of a holistic approach complementing antipsychotic medication, according to a UCL researcher.

Schizophrenia: Adolescence is the game-changer
Schizophrenia may be related to the deletion syndrome. However, not everyone who has the syndrome necessarily develops psychotic symptoms.

Study suggests overdiagnosis of schizophrenia
In a small study of patients referred to the Johns Hopkins Early Psychosis Intervention Clinic (EPIC), Johns Hopkins Medicine researchers report that about half the people referred to the clinic with a schizophrenia diagnosis didn't actually have schizophrenia.

The ways of wisdom in schizophrenia
Researchers at UC San Diego School of Medicine report that persons with schizophrenia scored lower on a wisdom assessment than non-psychiatric comparison participants, but that there was considerable variability in levels of wisdom, and those with higher scores displayed fewer psychotic symptoms.

Recognizing the uniqueness of different individuals with schizophrenia
Individuals diagnosed with schizophrenia differ greatly from one another. Researchers from Radboud university medical center, along with colleagues from England and Norway, have demonstrated that very few identical brain differences are shared amongst different patients.

Resynchronizing neurons to erase schizophrenia
Today, a decisive step in understanding schizophrenia has been taken.

Read More: Schizophrenia News and Schizophrenia Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.