Building a Better Antipsychotic Drug by Treating Schizophrenia's Cause: How Drugs Act On Dopamine-Producing Neurons
The classic symptoms of schizophrenia -- paranoia, hallucinations, the inability to function socially -- can be managed with antipsychotic drugs. But exactly how these drugs work has long been a mystery.
Now, researchers at Pitt have discovered that antipsychotic drugs work akin to a Rube Goldberg machine -- that is, they suppress something that in turn suppresses the bad effects of schizophrenia, but not the exact cause itself.
Grace hypothesizes that it's the schizophrenic brain's dopamine system working overtime. "Our recordings of dopamine neurons suggest that the dopamine system is turned up too high," says Grace. "That fits with human imaging studies in schizophrenics showing the dopamine system is overreacting."
Currently available antipsychotic drugs work by blocking dopamine receptors and stopping dopamine neurons from firing. "Using these drugs, we're fixing the overreactivity by causing the neurons to be inactive," says Grace. "It would be better to fix overreactivity by correcting what causes it.
"It's like fixing a car that's going too fast by taking out the engine instead of lifting your foot off the gas."
"What we're doing today, using antipsychotic drugs currently available, is putting a sort of patch several steps downstream from where we think the problem is," says Grace. "By using these animal models, we can start to work backwards to figure out why the drugs are having the effects they do. The next step to look further back and try to fix the problem at its source"
In the schizophrenic brain, it's not just the dopamine system that's hyperresponsive. The hippocampus is also hyperactive. Grace's research shows that this hippocampal hyperactivity probably causes the dopamine system to go into overdrive.
"This is consistent with the hypothesis that the hippocampus is overdriving the system, and antipsychotics are just pushing it over the edge to shut it down," he says. "This gives us an idea of where to go to make a better antipsychotic drug."
Although I really am heartened to see someone admitting their drugs don't address the cause of mental illness- these results are also consistent with two or more distinct yet interactive pathologies. The dopamine responsiveness can easily be explained by streptococcal autoimmunity. The drugs reduce symptoms because they shut down the receptors. The antibodies have nothing to bind to. If you treat these people's infections, the agonist activity really will be fixed at it's source.
The hippocampal activity may be related to gluten or casein autoimmunity.
And there is probably something else going on too. Some influenza or other viruses.
Free your mind. Stop thinking this is caused by one thing.