Disease Gene Linked to Evolution

Once you establish that a devastating disease has a heritable component, you are at pains to explain how the genetic predisposition has survived if the illness confers a reproductive disadvantage, right? The classic example is sickle cell anemia. Homozygotes have the illness; heterozygotes have sickle trait, which confers resistance to malaria, an endemic cause of excess mortality where sickle cell disease originated. Here’s a discovery about the genetics of schizophrenia that bears on this phenomenon; this is the first such explanation of which I am aware for a behavioral disease. For psychiatric diseases, I have been assuming that the selective advantage for those who get the ‘trait’ by inheriting one copy of the gene would be in the behavioral realm. For example, people have speculated that a ‘watered-down’ version of the bipolar (manic-depressive) genetic heritage might confer a selective advantage by giving its bearer a creative and mercurial temperament. At first reading I thought they were saying this ‘schizophrenia gene’ also confers malaria resistance (see the discussion in the comments to the post) but I realized that was a misreading; the article simply drew the same analogy to the sickle cell situation that I have above. The selective advantage of the gene being investigated here is not specified but may be in the realm of physical, not behavioral, health. I am on the lookout for further reports of this research.

“Approximately two percent of Caucasians have a gene segment variation that can cause a certain form of schizophrenia. Most people with the variation, known as a polymorphism, do not have the disease. A University of Iowa, Iowa City, study reveals a good prognosis for those who do have this form of schizophrenia. The researchers also found that this polymorphism is associated with overall benefits for human survival, and the initial mutation occurred in a single common ancestor about 100,000 years ago.

This has implications for finding better ways to treat this particular type of schizophrenia and possibly augmenting the positive influences of the polymorphism on human survival, as well as studying other gene defects.” (RedNova )

This is an aside, but when they refer to ‘types’ of schizophrenia with different symptoms, some psychiatrists, myself included, believe we are talking about distinct, heterogeneous diseases. Without going into too much detail, some people carrying that diagnosis have a disease such as the one described in this article, characterized predominantly by ‘positive’ symptoms such as hallucinations or paranoia. In the realm of schizophrenia, this is the type with the greatest evidence for heritability, and it has the best response to antipsychotic medication and the best overall prognosis. Other schizophrenics have a disease with more disturbance of the organization and logic of thought as well as ‘negative’ symptoms such as passivity, flatness and withdrawal. These are the schizophrenics who show abnormalities in the structure of their brains on MRI and other imaging studies; less genetic influence; less medication response; poorer premorbid functioning even in childhood; and overall worse prognosis. I believe that, in contrast to the ‘other’ schizophrenics who have a biochemical defect on the genetically encoded molecular level, usually inherited, which primarily affects synaptic communication between neurons, this latter class have a disease process, probably acquired or perhaps neurodegenerative, that affects the structure and gross organization (the ‘wiring’) of the brain. Research into the basic nature of the schizophrenic defect or defects and their etiology is hampered by lumping together patients with very different pathologies and processes.

As an analogy, what if our classification of diseases lumped chronic lower back pain sufferers and patients with migraine headaches as having a condition called dolorophrenia, because both had ‘pain’ and responded somewhat to various analgesic medications, and we did not recognize that that basis for classification was inadequate and the patients really had two (or more) very different pathological processes going on. If we took all these dolorophrenic patients and tried to do research into the genetics of their disease, did imaging studies of various parts of their anatomy, studied the longitudinal course of the illness, investigated the efficacy of other treatment approaches such as spinal surgery, looked at the question of whether there were perceptual or cognitive distortions during episodes, etc. etc., we would not be able to reach statistically significant conclusions about the nature of dolorophrenia because of its heterogeneity. That is the case, I think, with schizophrenia.