Study Shows Social Isolation Damages Brain Circuit and Leads to Phyciatric Disorders

If you boil all the components, loneliness might emerge as one of the biggest threats to mental health there is.​ Even as the world becomes more and more connected via digital platforms, people in our society are feeling an increased sense of isolation.

The pandemic, which made numerous countries force billions of people to social distance, isolate, and stop most activities, magnifies the need for understanding the mental health effects of social isolation and loneliness. While studies have demonstrated that social isolation during childhood, mainly, is harmful to adult brain function and behavior over the entire mammalian species, the fundamental neural circuit mechanisms have remained poorly understood.

Social Isolation and the Brain

A scientific team from the Icahn School of Medicine at Mount Sinai has now detected specific sub-populations of brain cells in the prefrontal cortex, a vital part of the brain that regulates social behavior that is required for normal sociability in adulthood and which are incredibly vulnerable to juvenile social isolation.

The research findings, which were published in the journal Nature Neuroscience, clarified a previously unrecognized part of these cells, known as medial prefrontal cortex neurons projecting to the paraventricular thalamus, the brain region that transmits signals to different components of the brain’s reward circuitry.

“In addition to identifying this specific circuit in the prefrontal cortex that is particularly vulnerable to social isolation during childhood, we also demonstrated that the vulnerable circuit we identified is a promising target for treatments of social behavior deficits,” says Hirofumi Morishita, MD, Ph.D., Associate Professor of Psychiatry, Neuroscience, and Ophthalmology at the Icahn School of Medicine at Mount Sinai, a faculty member of The Friedman Brain Institute and the Mindich Child Health and Development Institute, and senior author of the paper.

“Through stimulation of the specific prefrontal circuit projecting to the thalamic area in adulthood, we were able to rescue the sociability deficits caused by juvenile social isolation.”

In particular, the team of researchers found that, in male mice, two weeks of social isolation followed by immediate weaning leads to a failure to activate medial prefrontal cortex neurons projecting to the paraventricular thalamus throughout social exposure in adulthood.

Sociability Deficits and Psychiatric Disorders

Scientists discovered that juvenile isolation led to decreased excitability of the prefrontal neurons projecting to the paraventricular thalamus​ as well as enhanced inhibitory input from other related neurons, implying a circuit system emphasizing sociability deficits caused by social isolation.

To find out whether serious restoration of the activity of prefrontal projections to the paraventricular thalamus is enough to reduce sociability deficits in adult mice that underwent social isolation, the team used a method known as optogenetics to selectively stimulate the prefrontal projections to the paraventricular thalamus.

“We checked the presence of social behavior deficits just prior to stimulation, and when we checked the behavior while the stimulation was ongoing, we found that the social behavior deficits were reversed,” said Dr. Morishita.

Considering that social behavior issues are a common element of many neurodevelopmental and psychiatric disorders, the detection of these specific prefrontal neurons will indicate therapeutic targets for the improvement of social behavior deficits that a number of psychiatric disorders share.

This work was supported by the National Institutes of Health and the National Institute of Mental Health, and The Simons Foundation.

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