National Alliance on Mental Illness
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By Stephanie Corkett, NAMI Communications Intern
At the annual NAMI National Convention this past June, Dr. Jack McClellan, the Medical Director of Child Study and Treatment at the State Hospital of Child and Adolescents in Washington, presented the latest findings in the genetics of schizophrenia.
In the last five years, new research in the psychiatric field has led to enormous breakthroughs in mental illnesses including schizophrenia. McClellan recently finished a study examining the genome, (an individual’s entire genetic code consisting of more than 3 billion units of DNA), of individuals living with schizophrenia and comparing them to the genomes of people without the illness.
In the past, scientists believed that schizophrenia came from a certain gene that was passed down from parent to child; this process was called the Common Allele Model. The model suggested that each parent had the small genetic risk and when a child was born, the combined risks would result in their child having schizophrenia.
“This older model is questionable because if schizophrenia included completely heritable genes then it should not have been able to exist at all”
“This older model is questionable because if schizophrenia included completely heritable genes then it should not have been able to exist at all,” says McClellan. Considering the evolutionary process of natural selection, schizophrenia genes should not be passed on because most of those who are living with the disease do not have children. Eventually, the disease would be bred out of the human race.
McClellan’s study partially discredits this model. In his findings, McClellan noticed that of the 150 people he examined no one had the exact same mutations in their DNA, even siblings who were in the study together didn’t have the same genetic mutations that could have caused schizophrenia.
Looking at past research studies about schizophrenia, McClellan found two factors that could genetically contribute to schizophrenia: paternal age and rates of maternal famine. Two previous studies from the 1900s both showed that in times of famine, children had a twofold risk of having schizophrenia, this coupled with the fact that children are more likely to have a neural defects as the age of their father increases, are the only two factors that could genetically predispose a person towards schizophrenia.
McClellan realized that because schizophrenia wasn’t completely a heritable trait there had to be something else causing schizophrenia to appear, in turn he began looking at gene mutations.
McClellan found different combinations of mutations in every individual he tested. This means that because there is no common cause for schizophrenia everyone who is living with schizophrenia has a different strain and can exhibit different symptoms.
A normal human genome can have thousands of mutations in their genes. These mutations can either be deletions, where DNA code is deleted from DNA base pairs, or replications, where DNA is replicated more than one time when DNA is being created. “Most of these mutations are benign and won’t interfere with brain development or the body’s normal processes” says McClellan. McClellan believes that people who have schizophrenia have more mutations that people without mental illness, and that their mutations are a combination of a number of benign mutations that when combined produce mental illnesses.
The problem with this finding is that there is not a common mutation for schizophrenia. McClellan found different combinations of mutations in every individual he tested. This means that because there is no common cause for schizophrenia everyone who is living with schizophrenia has a different strain and can exhibit different symptoms. This is why people can show symptoms early or late in life and why not everyone reacts to medication for schizophrenia the same.
McClellan notes that the psychiatric field needs to move beyond categorizing someone by the disease and begin deducing how that person developed that disease. Because every case is different one general medication across the board isn’t effective for individuals living with schizophrenia.
“Until science can determine every single combination of mutations that can potentially cause schizophrenia they cannot begin to create medications to significantly see results in their patient’s symptoms,” notes McClellan.
McClellan has hope for the future of this research and believes that with continued support in the psychiatric field and extensive research into the different causes of schizophrenia, that the secrets behind the complex illness of schizophrenia will finally be revealed and understood.