Crossed Wires in the Brain as Potentially Reversible Cause of Schizophrenia

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Christoph Kellendonk, Ph.D., expert on schizophrenia research
Christoph Kellendonk, Ph.D.

The brain forms its thicket of connections early in life, but additions to its wiring diagram may be made even in adulthood, according to a study published in Neuron on January 8th. The researchers, led by two-time NARSAD Young Investigator Grantee, Christoph Kellendonk, Ph.D., Assistant Professor of Psychiatry at Columbia University, suggest that too many of these extra connections may contribute to schizophrenia.

The study, which included five NARSAD Grantees in total, focused on a mouse model of schizophrenia that mimics the surplus of dopamine, a chemical messenger, found in the disorder. This extra dopamine is found mainly in a part of the basal ganglia, a region deep within the brain important for movement, learning and motivation. These mice have problems with learning and motivation, similar to the cognitive and negative symptoms of schizophrenia.

Researchers found that the brains of these mice had extra connections between neurons that aren’t normally connected. These “crossed wires” scrambled the activity in these neurons, leading to unexpected effects on movement. The wayward connections could be unplugged in several ways, however. For example, blocking dopamine receptors with haloperidol, an antipsychotic medication, decreased the number of connections. This is evidence of the brain’s continuing capacity to adapt―its plasticity―that may be able to be targeted and enhanced with future therapies for schizophrenia.

Other NARSAD Grantees who took part in this research study included Nao Chuhma, M.D., Ph.D., Stephen Rayport, M.D., Ph.D., and Holly Moore, Ph.D. of Columbia University and Susanne E. Ahmari, M.D., Ph.D., of the University of Pittsburgh.

Read more about this research from the Schizophrenia Research Forum.

Read the abstract of this research study.

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Will this study be used in a clinical trial?

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