8-disorders-one-schizophrenia-complexity

New research suggests that what is commonly thought of as one disorder — schizophrenia — may in fact be eight different and distinct disorders.

Schizophrenia is a complex but rare mental illness characterized by a person experiencing hallucinations and/or delusions. It affects between 0.5 and 1 percent of the population at any given time and typically begins in a person’s early adulthood (their 20s).

Researchers from the Washington University School of Medicine analyzed the DNA of 4,000 people who were previously diagnosed with schizophrenia. After their analysis, they concluded that what we have traditionally considered to be one disorder may in fact be eight separate, distinct genetic disorders.

Furthermore, the researchers suggested that these eight different disorders can combine into clusters, each of which may carry different risk profiles for schizophrenia.

“There isn’t just this one kind of schizophrenia,” noted lead researchers C. Robert Cloninger, “but actually several different syndromes where some people have positive symptoms like hallucinations and delusions [and] others have negative symptoms where they’re not able to think logically and these different syndromes are associated with different groups of genes.”

The scientists in the new study took a different approach to examining the possible genetic causes of schizophrenia. Typically research has examined single gene or gene sequences for clues. But the new research examined how different symptoms seemed to be caused by specific configurations of genetic variations.

In all, the researchers analyzed nearly 700,000 sites within the genome where a single unit of DNA is changed, often referred to as a single nucleotide polymorphism (SNP). They looked at SNPs in 4,200 people with schizophrenia and 3,800 healthy controls, learning how individual genetic variations interacted with each other to produce the illness.

In some patients with hallucinations or delusions, for example, the researchers matched distinct genetic features to patients’ symptoms, demonstrating that specific genetic variations interacted to create a 95 percent certainty of schizophrenia.

In another group of people with schizophrenia, they found that disorganized speech and behavior were specifically associated with a set of DNA variations that carried a 100 percent risk of schizophrenia

The causes of schizophrenia, like most mental disorders, are poorly understood at present. Researchers currently believe that about 80 percent of the risk for schizophrenia is inherited. While genetics is understood to be a component of the cause of schizophrenia and some other mental illnesses, exactly what genes are responsible has been a cat-and-mouse game for decades. Dozens of genes and gene variations have been indicted for schizophrenia’s cause, resulting in a confusingly complex picture.

Although individual genes have only weak and inconsistent associations with schizophrenia, groups of interacting gene clusters create an extremely high and consistent risk of illness, on the order of 70 to 100 percent. That makes it almost impossible for people with those genetic variations to avoid the condition.

In all, the researchers identified 42 clusters of genetic variations that dramatically increased the risk of schizophrenia.

Then they divided patients according to the type and severity of their symptoms, such as different types of hallucinations or delusions, and other symptoms, such as lack of initiative, problems organizing thoughts or a lack of connection between emotions and thoughts. The results indicated that those symptom profiles describe eight qualitatively distinct disorders based on underlying genetic conditions.

The investigators also replicated their findings in two additional DNA databases of people with schizophrenia, an indicator that identifying the gene variations that are working together is a valid avenue to explore for improving diagnosis and treatment.

The new research could open the door to better understanding the underlying foundation of schizophrenia.

Source: Washington University School of Medicine