Despite many attempts to figure out its underlying mechanisms, schizophrenia remains one of the most poorly understood mental illnesses. Yet, a study published in the journal Neuron may have gotten a step closer after finding deficits in social memory — a key feature of schizophrenia — may be caused by a decrease in the number of inhibitory neurons in the brain.

Researchers from Columbia University's Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University Medical Center (CUMC), and the Universite Paris Descartes found a decrese of inhibitory neurons in a lesser-explored region of the brain's memory center may be to blame for more difficult symptoms, including reduced motivation, decreased emotional capacity, and social withdrawal. Scientists have long suspected the illness originates somewhere in the brain's hippocampus, resulting in extensive examination of nearly every region of that brain structure. One exception, they found, was a miniscule area called CA2.

"Smaller and less well-defined that other parts of the hippocampus, CA2 was like a small island that was depicted on old maps but remained unexplored," said Dr. Vivien Chevaleyre, group leader in neuroscience at the Universite Paris Descartes and a lead author on the paper, in a statement.

Previous studies have suggested a possible association between the mysterious CA2 region and schizophrenia. The area is associated with vasopressin, a hormone associated with sexual bonding, motivation, and other important social behaviors; many of which become impaired after schizophrenia surfaces. Post-mortem examinations of those with the disorder also revealed a decrease in the number of CA2 inhibitory neurons, while the rest of the hippocampus showed no such changes. The significance of this observation, however, remained unclear.

To investigate, researchers performed several behavioral and electrophysiological experiments on a mouse model of schizophrenia created at CUMC. They observed a significant increase of inhibitory CA2 neurons compared to normal, healthy mice — a very similar observation to those seen in post-mortem examinations of humans with schizophrenia. In addition, the team found the schizophrenia-model mice demonstrated a reduced capacity for social memory, raising the idea that changes in CA2 could account for some of the odd social behaviors occurring in those with the disorder.

"Even the timing of the emergence of symptoms in the mice — during young adulthood — parallels the onset of schizophrenia in humans," explained Dr. Joseph Gogos, a professor of physiology and neuroscience at CUMC, a principal investigator at the Zuckerman Institute and a lead study author.

The discovery potentially opens up a new avenue for schizophrenia research that could lead to earlier diagnosis for patients.

Source: Piskorowski R, Nasrallah K, Diamantopoulou A, Mukai J, Hassan S, Siegelbaum S, et al. Age-Dependent Specific Changes In Area CA2 Of The Hippocampus And Social Memory Deficit In A Mouse Model Of The 22q11.2 Deletion Syndrome. Neuron. 2016.