Dopamine Is Key to the Mystery of Metabolic Dysfunction in Psychiatric Patients

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ngd- All current psychiatric medications affect more than the “targeted” parts of the brain. SSRIs alter the serotonin nerves in the gut and then alter the brain through the vagus nerve…

Summary: Anti-psychotic drugs do not only block dopamine signaling in the brain, they also block dopamine signaling in the pancreas. Blocking dopamine signaling in the pancreas leads to uncontrolled production of blood-glucose regulating hormones, increasing obesity and diabetes risks.

Why do patients who receive antipsychotic medications to manage schizophrenia and bipolar disorder quickly gain weight and develop prediabetes and hyperinsulemia? The question remained a mystery for decades, but in a paper published today in Translational Psychiatry, researchers from the University of Pittsburgh School of Medicine finally cracked the enigma.

Antipsychotic drugs, scientists showed, not only block dopamine signaling in the brain but also in the pancreas, leading to uncontrolled production of blood glucose-regulating hormones and, eventually, obesity and diabetes.

“There are dopamine theories of schizophrenia, drug addiction, depression and neurodegenerative disorders, and we are presenting a dopamine theory of metabolism,” said lead author Despoina Aslanoglou, Ph.D., a postdoctoral fellow at Pitt’s Department of Psychiatry. “We’re seeing now that it is not only interesting to study dopamine in the brain, but it is equally interesting and important to study it in the periphery.”

Dopamine is a neurotransmitter that acts as a chemical messenger between neurons and is commonly known to play a role in pleasure, motivation and learning. And antipsychotic medications–such as clozapine, olanzapine and haloperidol–relieve hallucinations and delirium by blocking a subtype of dopaminergic receptors in the brain called D2-like receptors and preventing dopamine molecules from causing neurological effects.

But, as Aslanoglou and senior author Zachary Freyberg, M.D., Ph.D., assistant professor of psychiatry and cell biology at Pitt, found, it’s not so simple.

“We still don’t really understand how dopamine signals biologically,” said Freyberg. “Even decades after dopamine receptors have been discovered and cloned, we still deploy this ‘magical thinking’ approach: something happens that’s good enough. We use drugs that work on dopamine receptors, but how they intersect with this ‘magical system’ is even less understood.”

The human pancreas contains miniature structures called pancreatic islets, which are made up of alpha and beta cells whose function is to produce and secrete hormones that regulate blood glucose. Alpha cells produce glucagon to raise blood glucose, and beta cells produce insulin to lower blood glucose back to normal.

If even one player in the glucose-regulating machinery breaks, our bodies begin to suffer. Low blood glucose makes us feel dizzy and faint, while high blood glucose–when sustained for a long time–causes diabetes and other complications in the cardiovascular system.

And, as it turns out, dopamine can tip the scales.

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