Genetic Variant May Explain What Causes Schizophrenia

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A single genetic variant is responsible for many of the classic symptoms of schizophrenia, a discovery that researchers say provides new insights into the molecular basis for the disease and could potentially lead to new treatments.

Scott Soderling, PhD, a neuroscientist at Duke University in Durham, N.C., and colleagues found that mice that were genetically modified to lack the Arp2/3 gene variant all suffered from psychosis, agitation, and problems with short- and long-term memory. That gene is responsible for the formation of neurons, which connect brain cells.

The researchers also found that three brain abnormalities in the mice are also present in people with schizophrenia, they reported in the journal Nature Neuroscience. Those are: fewer than normal “dendritic spines” in the cells of the brain’s frontal cortex; overactive excitatory neurons; and elevated levels of the neurotransmitter dopamine.

In their study, the brain cells of the variant-lacking mice rewired themselves to go around missing dendritic spines. But when this happened, the cells bypassed a filter than normally keeps excitatatory impulses in check. This also led to poorer performance on memory tests. And the hyperactive cells ended up sending signals into a part of the brain that contains a large amount of dopamine.

While the antipsychotic haloperidol has been used to reduce the amount of dopamine in the brain, Soderling said that excessive dopamine is not at the root of schizophrenia, but rather, a pattern of errors committed by brain cells is.

Depression, bipolar disorder, and schizophrenia have more in common than previously thought.
Genetic Variant May Explain What Causes Schizophrenia

Schizophrenia is one of psychiatry's most puzzling afflictions, with a complex of symptoms that goes far beyond its hallmark hallucinations and delusional thinking.

But new research has found connections among several of schizophrenia's peculiar collection of symptoms — including agitation and memory problems — and linked them to a single genetic variant among the hundreds thought to heighten risk of the disorder.

The findings offer new insights into the molecular basis for schizophrenia and could lead to treatments for the disease that are more targeted and more comprehensive.

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