Health & Medicine - Posted by David Salisbury-VU on Tuesday, June 15, 2010 9:15 - 4 Comments 
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(2 votes, average: 5.00 out of 5) Loading ...Impaired insulin signaling links food to mood
Scientists have discovered a molecular link between impaired insulin signaling in the brain and schizophrenia-like behavior in mice. The findings offer a new perspectice on psychiatric and cognitive disorders that affect diabetics. (Credit: iStockphoto)
VANDERBILT (US)—Defects in insulin action—which occur in diabetes and obesity—could directly contribute to psychiatric disorders like schizophrenia.
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Scientists have found a molecular link between impaired insulin signaling in the brain and schizophrenia-like behaviors in mice.
The findings, reported recently in PLoS Biology, offer a new perspective on the psychiatric and cognitive disorders that affect patients with diabetes and suggest new strategies for treating these conditions.
“We know that people with diabetes have an increased incidence of mood and other psychiatric disorders,” says Kevin Niswender, assistant professor of medicine and molecular physiology and biophysics at Vanderbilt University.
“We thought that those co-morbidities might explain why some patients have trouble taking care of their diabetes.”
Aurelio Galli, professor of molecular physiology and biophysics, was among the first to show that insulin—the hormone that governs glucose metabolism in the body—also regulates the brain’s supply of dopamine—a neurotransmitter with roles in motor activity, attention, and reward.
“Something goes wrong in the brain because insulin isn’t signaling the way that it normally does,” Galli explains.
Disrupted dopamine signaling has been implicated in brain disorders including depression, Parkinson’s disease, schizophrenia, and attention-deficit hyperactivity disorder.
Now, Galli and Niswender have pieced together the molecular pathway between perturbed insulin signaling in the brain and dopamine dysfunction leading to schizophrenia-like behaviors.
The researchers developed mice with an insulin-signaling defect only in neurons and found that the mice have behavioral abnormalities similar to those frequently seen in patients with schizophrenia.
They also showed how defects in insulin signaling disrupt neurotransmitter levels in the brain—the mice have reduced dopamine and elevated norepinephrine in the prefrontal cortex, an important area for cognitive processes.
These changes resulted from elevated levels of the transporter protein (NET) that removes norepinephrine and dopamine from the synaptic space between neurons.
By treating the mice with NET inhibitors (drugs that block NET activity), the investigators were able to restore normal dopamine levels and behaviors.
Clinical trials of NET inhibitors in patients with schizophrenia are already under way, Galli says, and these new data provide mechanistic support for this approach.
Understanding the molecular link between insulin action and dopamine balance offers the potential for novel therapeutic approaches.
“Dysregulation of this insulin-signaling pathway—because of type 1 diabetes, because of a high-fat diet, because of drugs of abuse, because of genetic variations—may put a person on the road to neuropsychiatric disorders,” Galli says.
More Vanderbilt University news: www.vanderbilt.edu/news
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4 Comments
Martin P. Serna
Erika L
This is really great news! I have PCOS (Poly Cystic Ovarian Syndrome) which is thought to be caused by or contributed to by insulin resistance. PCOS causes many hormonal imbalances. It makes me gain weight rediculously fast, have physical exhaustion before my muscles have had a chance to be worked to where they should be tired, menstrul irregularities, infertility and severe mood swings! I also have brain fog where it is hard to problem solve or learn new things or even remember basic things.
All of the physical stuff I can deal with. I never wanted children and I was always a sporty tom-boy type girl so being far from having a nice figure isn’t too horrible. I do miss having energy but it’s the mental part that is the worst. I miss precious mental and emotional stability. There is something that is really effecting my mood and ability to think with pcos. The majority of other women with pcos have it too.This wreaks havoc on my mood. All of the medications I have tried in the past have offered no relief. Most women with pcos have the same problem. I think it is insulin resistanceand its effects on the brain like a lot of science is pointing to. Since pcos is mainly from insulin resistance in the body what stops the brain from also becoming resistant to insulin in people with pcos.
I do not hear any voices or anything but the anxiety, panic and depression can be so horrible. It is preventing me from holding a job. Like I said all the medications I’ve tried haven’t helped and therapy does nothing for it. Diet and exercise can help as long as I don’t overdo it. Exercising too hard can take days to recover from and make my mood so much worse…unbearable really.
Maybe the researchers will also be able to help people with all types of neurological problems from insulin resistance like alzheimers (which has also been linked to insulin resistance and it’s effects on the brain) schizophrenia and others.
Keep up the good work! I hope they continue to report on your findings with the NET inhibitors in humans.
Tif Clegg
It has been known for many years that food and mood are related . Food for some is a cure (albeit a poor one ) for anxiety , depression , fear , tension and becomes a habit . Habit formation is a big part of the overeaters world . Whenever one eats for reasons other than hunger there are problems , For many of us a hamburger cures even our subliminal problems , let alone our conscious pains . Eating for emotional reasons causes overweight and increases insulin resistance . Some bipolar people try to control mood with food . Psychosis can be unmasked by food restriction . Despair after eating is common in the obese . My view is that understanding all this requires a systems approach . Yes neurological changes are occurring along with learning/not learning/ habit/attempts to control emotion / old learning in the family and on and on .
It is the interaction of many factors in a very complex way that accounts for behaviour , and that includes genetics .
Pauline
just to say that the majority of life altering medication has been tested on animals, I am not in favour of it but the fact remains that if the drugs are going to save lives or improve lives we would be complaining if we couldn’t have access to them.
If the authors of this study were really studying nature and not just giving a science answer for a science caused problem, they would know that in biology nothing is mechanistic. There is Behavioralism somewhere in the backround. No nutrition studying here. Where is the funding for their study coming from, again?
I’d hate to be the mice in their study. Crippled at birth and then exterminated after use. This truly is the pardigm for humans, also.