May 2019Research at the Lady Davis Institute

Developmental abnormalities in the brain offer clue to schizophrenia

An underdeveloped area in the brains of individuals with schizophrenia has been revealed as the first clear anatomical signature for the disease, says a study by a leading researcher at the Lady Davis Institute.

The findings by Dr. Hyman Schipper, published in The Neuroscientist, indicate that the dentate gyrus—in a region of the brain known as the hippocampus—is noticeably underdeveloped in people with schizophrenia. His research is based on a close examination of the hippocampus in humans and mice.

Dr. Schipper has proposed that when immature properties in this region of the brain are retained into adulthood, they could be responsible for the disease. Schizophrenia does not usually present in men until they are in their 20s, and women in their 20s or 30s.

“This abnormality may account for many cardinal symptoms of schizophrenia,” Dr. Schipper says, “because the dentate gyrus is associated with the brain’s capacity to separate and process sensory stimulation and to distinguish the real from the delusional.”

Molecular and electrophysiological abnormalities in the dentate gyrus have already been identified in schizophrenic patients, but no one had previously described a specific anatomical anomaly.

“Since the dentate gyrus is anatomically normal until adolescence in schizophrenia and in animal models of the disease, it appears as though developmental arrest within this brain structure, manifesting soon after adolescence, may be responsible for the emergence of psychotic symptoms,” Dr. Schipper elaborates.

There is currently no validated biomarker for diagnosing schizophrenia, but a high-resolution MRI might allow for diagnosis, based upon the architecture of the dentate gyrus. This promises to be more efficient and accurate than the current practice, which consists of a clinical (psychiatric) evaluation of an individual in the midst of psychosis.

Drug therapies, which are shown to be effective in preventing maturational arrest of the dentate gyrus in animal models, could be tested in humans who are at risk for schizophrenia. This would offer an unprecedented opportunity to possibly influence the pathogenesis of the disease and not merely its symptoms.

Ayda Tavitian, a Ph.D. candidate in Dr. Schipper’s lab, first recognized the immature hippocampal morphology, winning her the IPN Star award from McGill’s Integrated Program in Neuroscience for her work on this paper.

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