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New evidence for a neuronal link between insulin-related diseases and schizophrenia

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diabetes psychiatric schizophrenia insulin dopamineWhen the body does not properly manage insulin levels, diabetes and other metabolic disorders are familiar outcomes. That hormonal imbalance, however, has also been linked to a higher risk for psychiatric disorders, such as schizophrenia. And a new study has uncovered a potential pathway by which this metabolic hormone can upset the balance of a key neurotransmitter.

"We know that people with diabetes have an increased incidence of mood and other psychiatric disorders," Kevin Niswender, an endocrinologist at Vanderbilt University Medical Center and coauthor of the study, said in a prepared statement. Previous researchers, including Aurelio Galli, a neurobiologist at Vanderbilt, had found that insulin was affecting more than blood sugar levels.

"Something goes wrong in the brain because insulin isn’t signaling the way that it normally does," Galli, a coauthor of the new paper, published online June 8 in the journal PLoS Biology, said in a prepared statement. Although schizophrenia is a complex disease that is thought to have a variety of individual genetic and epigenetic causes, these researchers and others have proposed that a common thread is too little dopamine, a neurotransmitter that is involved in movement, reward and motivation.

But just how, molecularly, insulin and dopamine dysfunctions might be linked has yet to be settled.

In the new study, the researchers focused on the protein kinase Akt, which plays a role in cell signaling and has been linked to schizophrenia as well as to diabetes and obesity. It is controlled by hormones, neurotransmitter receptors and growth factors. To study Akt’s possible role in schizophrenia and its relation to insulin dysregulation, the researchers created a line of transgenic mice that had poor Akt signaling, leading to schizophrenia-like behaviors.

The researchers also found that the modified mice had increased transportation of another neurotransmitter norepinephrine (which also acts as a stress hormone) and a deficit of dopamine in their brains, a condition known as hypodopaminergia.

"We believe the excess [norepinephrine transporters are] sucking away all of the dopamine and converting it to norepinephrine, creating this situation of hypodopaminergia in the cortex," Galli said.

And when the researchers inhibited the norepinephrine transporter in these Akt knock-out mice, "we could reverse the cortical hypodopaminergia and behavioral deficits," they noted in the study.

"Taken together, this work supports the potential for targeting both Akt and the norepinephrine transporter for treating dopamine-related mood disorders," the researchers concluded. They also point out clinical trials are already testing norepinephrine transporter blockers for their effectiveness in restoring dopamine balance in schizophrenics.

The molecular pathway might also shed some light on behavioral issues associated with diabetes and other insulin-related metabolic disorders. "We thought that those co-morbidities might explain why some patients have trouble taking care of their diabetes," Niswender said.

Image of dopamine pathways in the brain courtesy of Wikimedia Commons/NIDA

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  1. 1. sds 7:57 pm 06/8/2010

    Maybe success rate for the insulin shock therapy used to treat schizophrenia in the 1940s and 1950s in the USA can be explained by this new research.

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  2. 2. Petra 2:22 pm 06/10/2010

    I’m very thankful for this research. When my husband had severe mood swings due to his diabetes I literally went in search of a book as to "how to live with diabetics" and found nothing. Eight years later he went crazy and attacked my daughter and when consulting with a doctor through the American Diabetes Assn he said he didn’t think he had schizophrenia despite the fact that it ran in his family. As he became quite dangerous and I divorced him, but it’s good to see a greater understanding for those who live with diabetics and those who have it need to know sometimes they are over the top.

    Though I’m curious to know if those under study had irregular blood sugar levels thus exacerbating the propensity to behave poorly or become a danger to those around them.
    And what might be a course of treatment? Psychiatric meds perhaps?

    Thanks for your research! It’s brought validation to a long held question I had in understanding more about this condition and given many more will have it in the future; caretakers, wives and families need to know it’s not unheard of and seek greater assistance.

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  3. 3. sunnystrobe 6:18 am 06/16/2010

    Food for thought indeed! Since sugar is our brain fuel, a too-muchness of it acts as a dangerous drug, wreaking havoc in our entire body- from top to toe- as diabetics know. What the general public, however, doesn’t get told is the ubiquity of sugar in all processed food- we get literally baited by sugar, and are consuming a hundred times more than our ancestors, with dire consequences to our national health..
    Two of my dearest friends have become schizophrenic, and this probably after nutrient-deficient body stress; the lady friend ate mainly white rice and adamantly refused any advice to eat fresh fruit and vegetables. In the light of medical evidence, it is absolutely vital to promote a nutritional rationale which is suited to our human genome – vide

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  4. 4. femtobeam 7:47 am 06/16/2010

    Insulin crosses the Blood/Brain barrier, unlike most other substances, and can carry any number of chemical compositions with it as a transport to affect neurons.

    A comprehensive study needs to be done to determine to what extent EM radiation has on the functioning of the brain in relation to insulin and blood sugar levels. The cause of the diabetes, the insulin levels and symptoms of many so-called mental disorders attributed to genetics, can then be disqualified as attributed to chemical substances which cross the Blood/Brain barrier with the Insulin transport, compared with those caused by EM radiation, affecting brain potentials and neuronal pathways.

    Can insulin be regulated by electricity and electric potential (brain wave) disruption using targeted EM radiation or not? If so, the cause of the observable symptoms is electromagnetic and/or compounds carried across the BBB along with insulin, not genetic. The degree to which this is so can be quantified to include blood sugar levels and intake over time between groups in a blind study.

    Such a study is unlikely to be underwritten by a pharmaceutical company but rather by a telecommunications or advertising agency… on the prowl for opportunities in remote medicine, mind control and neuromarketing.

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