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Schizophrenia Not One Disease, New Genetic Evidence Shows

Schizophrenia Not One Disease, New Genetic Evidence Shows: Fifteen of the 48 patients (31.25%) carried rare or novel variants in one or more of the four genes, and these subgroups of patients had significantly different symptoms.

One gene is PTPRG (receptor-type tyrosine-protein phosphatase gamma), which encodes a protein that allows nerve cells to connect as they form nerve networks. Patients with rare variants in this gene experienced earlier onset of relatively severe psychosis and had a history of learning disabilities. Despite high intelligence in some, they showed cognitive deficits in working memory, the researchers say.

Another influential gene is SLC39A13 (zinc transporter family 39 member 13). Patients with mutations in this gene also experienced early onset of schizophrenia, but they showed globally disrupted cognition and the most severe psychopathology, including negative symptoms and severe suicide attempts. They had the lowest intelligence and the least educational attainment, consistent with a developmental disorder, the researchers report.

Patients with variants in a third influential gene, ARMS/KIDINS220 (ankyrin repeat-rich membrane-spanning protein), showed early promise, and many attended college. They then experienced cognitive decline, consistent with a degenerative process.

Patients with variants in a fourth influential gene, TGM5 (transglutaminase 5), had less severe symptoms but often experienced attention-deficit disorder during childhood, and processing speed was slow in these patients.
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