Vineyard Brains

in News
July 11th, 2011

Going on vacation with my family for thirteen days was both exciting and daunting. The West Coast adventure was extremely appealing and I couldn’t wait to see the Grand Canyon, explore Yosemite National Park, and drive a convertible down the Pacific Coast Highway. But where was I going to get my brain fix? The Scientific American issue I bought for the flight to Phoenix wasn’t doing it for me. Some hope was gained at The Exploratorium, a hands-on science museum in San Francisco that managed to convince my thirteen-year-old sister that neuroscience might be almost potentially cool, but it wasn’t until a trip to Sonoma County that my curiosity was finally piqued.

Tiger the horse and I were riding along on a vineyard tour and I was talking to the tour guide about school. I’ve got yet another new response to “I’m studying neuroscience”: the tour guide told me about his son’s mysterious mental illness that may or may not be schizophrenia and we rode through wine country discussing psychiatrists, Thorazine, thought disorders and SSRIs. All in all, a good day.

This conversation got me wondering about the kinds of challenges psychologists and psychiatrists face when having to diagnose patients with schizophrenia. All the clinicians have to go on are whatever behavioral abnormalities make themselves apparent. But how do you weed out schizophrenia from other kinds of psychosis (some of which may respond to the typical treatment for schizophrenia)?

In March, scientists in Finland published a paper in Genome Medicine in which they described a study done on patients with DSM-IV primary psychosis – disorders that included schizophrenia, other non-affective psychosis (ONAP) and affective psychosis. The researchers measured cholesterol (HDL and LDL), triglycerides, glucose, insulin, C-reactive protein (CRP) and cotinine. They also measured blood pressure, weight, and waist circumference as well as asking for the participants’ use of butter versus vegetable oil, fat content in milk products, and use of raw vegetables. The study investigated various metabolic processes that could be associated with schizophrenia, with the hope that certain metabolites have the potential for use as diagnostic tests for the disorder.

Schizophrenics tend to have a high level of fasting total triglycerides and show insulin resistance, but this feature is usually seen as a side effect of antipsychotic medication. However, other recent studies have shown abnormal insulin secretion and glucose response, along with diabetes risk, to be common in new schizophrenia patients who have yet to start treatment. One study, published in Molecular Psychiatry last year, showed that despite normal to slightly elevated glucose levels, untreated schizophrenia patients showed heightened levels of insulin and related proteins (the precursor proinsulin, the intermediate des31,32-proinsulin, C-peptide, which links the A and B chains of insulin, and chromogranin A, a precursor to other secretory hormones) where their bipolar counterparts did not. The extra insulin could certainly have a negative effect on brain function.

In the Genome Medicine study, branched-chain amino acids (BCAAs) from metabolic cluster MC3 were elevated in the schizophrenia patients. BCAAs are important to insulin secretion and they also compete with aromatic amino acids trying to cross the blood-brain barrier, suggesting a possible mechanism for psychosis. A drop in concentration of the amino acids needed to make catecholamines and serotonin in the brain (tyrosine and tryptophan, respectively) could be part of the problem. Perhaps this is why the tour guide’s son had spent some time on SSRIs when a clinician thought he was schizophrenic – although the drugs didn’t do much for his problem.

Catecholamines and serotonin don’t make up the whole story, which could have been why the SSRIs didn’t help this young man’s illness even if he definitely had schizophrenia. Another pathway that this article links to the schizophrenia mystery involves the up-regulation of proline that is apparent in schizophrenia patients. Many patients seem to be predisposed to variations of the PRODH gene that cause a decrease in proline oxidase. The result (excess proline in the brain) has been associated with cognitive dysfunction.

Too much proline and too much insulin, BCAAs competing with tyrosine and tryptophan – I’d never read this before, and my tour guide told me that his son was doing well on Thorazine, a drug (as I’d learned in school) was used to put the brakes on dopamine in patients with which disorder? Schizophrenia. 

What about dopamine, then? It turns out that the hypothesis relating overabundance of dopamine to schizophrenia is somewhat outdated. Studies have shown that patients who did not benefit from antipsychotics, like Thorazine, still had 90% of their D2 dopamine receptors blocked. Conversely, it has been demonstrated that patients that did benefit from treatment had low levels of D2 blockade. In addition, the up-regulation of D2 receptors noted in post-mortem examination of schizophrenics’ brains could have been the result of the treatment they were on, not of the illness itself. Imaging of living, yet-untreated schizophrenics has not shown an increase in D2 receptors. It seems likely, then, that whatever the Thorazine is treating in my tour guide’s son was not schizophrenia. The mystery as to what the disorder actually is remains…but now I know why there is a mystery to begin with!

One Step Closer to a Diagnostic Test for Schizophrenia – Science Daily

Metabolome in Schizophrenia and Other Psychiatric Disorders: a General Population-based Study – Genome Medicine

Increased Levels of Circulating Insulin-Related Peptides in First Onset, Antipsychotic Naive Schizophrenia Patients – Molecular Psychiatry

Dopamine and Antipsychotic Drug Action Revisited – The British Journal of Psychiatry

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3 Comments on Vineyard Brains

  • You’ve made some good points there. I looked on the internet for more information about the issue and found most people will go along with your views on this website.

  • Hello,
    I was wondering if there are any studies that researched the effectiveness of the various schizophrenia medications. Is there anything in the diagnosis of schizophrenia that can be used to determine which drug will likely have the best effect for the patient?

    Many thanks,

  • It does not genuinely make a difference a lot, so that as it progresses every thing kind of draws jointly. Plumbing

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