The media is abuzz today with news of a scientific breakthrough in schizophrenia research. Researchers at Harvard, Massachusetts General Hospital, Boston Children’s Hospital, and the Harvard/MIT Broad Institute have uncovered a relationship between the genetics and molecular mechanism of schizophrenia.
This is huge news.
For years, scientists have been searching for a mechanism by which schizophrenia develops. Here’s some of what we knew about the etiology of schizophrenia before this study:
- It’s heritable. It is associated with genetic variation at specific sites on DNA.
- The outer layer of the brain (cortex) is thinner.
- There are decreased connections between neurons (brain cells).
- It typically emerges in adolescence/early adulthood.
But never have researchers been able to uncover a physical pathway by which schizophrenia develops. Now, with the help of a very large genetic database, mice, brains, and lots of ingenuity, researchers have discovered one.
Here are the basics.
- Most schizophrenics have a tiny piece of genetic code that leads to the production of too much of a protein called C4-A.
- C4-A is involved in the “complement cascade,” an important part of the immune system that helps the body kill pathogens and get rid of infected or malfunctioning cells.
- C4-A is also deposited on synapses in the brain (connections between neurons) to get rid of connections that we do not need.
- This “pruning” of connections is an important part of adolescent brain development.
- The authors postulate that pruning is overactive in schizophrenia because there is too much C4-A, which is likely why the disease first shows up in late adolescence/early adulthood and why the brain’s outer layer is thinner.
Discoveries of illness pathways are exciting: they’re the first step to better treatments or even cures. Before we have pathways, all we can do is treat symptoms. We treat schizophrenia with antipsychotics like Haldol or Risperidone; these drugs reduce psychotic symptoms, but they have no effect on the so-called “negative symptoms” of schizophrenia -- cognitive decline and apathy, for example -- that are the major debilitating symptoms of the disease.
Now that a pathway has been identified, we can begin the development of disease-modifying medications and hopefully halt/slow the development of schizophrenia. This is a complicated and uncertain task, but we aren’t starting from scratch: we know a lot about this part of the immune system already and a few drugs that target similar proteins exist.
But what’s most exciting to me about this discovery is that it marks the beginning of a new era of psychiatry. In the past decade, technology has enabled the proliferation of genetic and epigenetic research. We’ve discovered myriad genetic variations that predispose people to developing mental disorders like depression, bipolar disorder, schizophrenia, and even personality disorders. But the research seems to stop there.
Too infrequently have researchers been able to take the next step and figure out what the genetic variation means and how it affects biological pathways. Now that this has been done once, it’s going to be done again and again and again.
The Big Bang of psychiatry has begun.