Suspect gene corrupts neural connections

iPSC-induced neurons drom Schizophrenia patients with DISC1 (Disrupted In Schizophrenia-1) gene mutation, , expressed 80 percent less DISC1 protein compared to members without the mutation. These mutant neurons showed deficient cellular machinery for communicating with other neurons at synapses.

The researchers traced these deficits to errant expression of genes known to be involved in synaptic transmission, brain development, and keyextensions of neurons where synapses are located. Among these abnormally expressed genes were 89 previously linked to schizophrenia, bipolar disorder, depression, and other major mental disorders. This was surprising, as DISC1's role as a hub that regulates expression of many genes implicated in mental disorders had not previously been appreciated.

The clincher came when researchers experimentally produced the synapse deficits by genetically engineering the DISC1 mutation into otherwise normal iPSC neurons – and, conversely, corrected the synapse deficits in DISC1 mutant iPSC neurons by genetically engineering a fully functional DISC1 gene into them. This established that the DISC1 mutation, was, indeed the cause of the deficits.

Researchers reported their discovery in the journal Nature.