Keywords

synapse, neuropil, schizophrenia, MRI, gene, dendritic spine

Abstract

Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitution significantly diminished the protein's ability catalyze the activation of Rac1. Contrary to wild-type kalirin-7, kalirin-7-D1338N failed to increase spine size and density. Both subjects carrying the polymorphism displayed reduced cortical volume in the superior temporal sulcus (STS), a region implicated in schizophrenia. Consistent with this, mice with reduced kalirin expression showed reduced neuropil volume in the rodent homolog of the STS. These data suggest that single amino acid changes in proteins involved in dendritic spine function can have significant effects on the structure and function of the cerebral cortex.

Document Type

Peer-Reviewed Article

Publication Date

2015-03-16

Permanent URL

http://hdl.lib.byu.edu/1877/8815

Language

English

College

Family, Home, and Social Sciences

Department

Psychology

University Standing at Time of Publication

Assistant Professor

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Psychology Commons

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