Researchers discover a specific brain circuit damaged by social isolation during childhood

Study in mice shows long-lasting effects and points the way to potential treatments

August 31, 2020

Science Daily/The Mount Sinai Hospital / Mount Sinai School of Medicine

Loneliness is recognized as a serious threat to mental health. Even as our world becomes increasingly connected over digital platforms, young people in our society are feeling a growing sense of isolation. The COVID-19 pandemic, which forced many countries to implement social distancing and school closures, magnifies the need for understanding the mental health consequences of social isolation and loneliness. While research has shown that social isolation during childhood, in particular, is detrimental to adult brain function and behavior across mammalian species, the underlying neural circuit mechanisms have remained poorly understood.

A research team from the Icahn School of Medicine at Mount Sinai has now identified specific sub-populations of brain cells in the prefrontal cortex, a key part of the brain that regulates social behavior, that are required for normal sociability in adulthood and are profoundly vulnerable to juvenile social isolation in mice. The study findings, which appear in the August 31 issue of Nature Neuroscience, shed light on a previously unrecognized role of these cells, known as medial prefrontal cortex neurons projecting to the paraventricular thalamus, the brain area that relays signals to various components of the brain's reward circuitry. If the finding is replicated in humans, it could lead to treatments for psychiatric disorders connected to isolation.

"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, PhD, 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."

Specifically, the team found that, in male mice, two weeks of social isolation immediately following weaning leads to a failure to activate medial prefrontal cortex neurons projecting to the paraventricular thalamus during social exposure in adulthood. Researchers found that juvenile isolation led to both reduced excitability of the prefrontal neurons projecting to the paraventricular thalamus and increased inhibitory input from other related neurons, suggesting a circuit mechanism underlying sociability deficits caused by juvenile social isolation. To determine whether acute restoration of the activity of prefrontal projections to the paraventricular thalamus is sufficient to ameliorate sociability deficits in adult mice that underwent juvenile social isolation, the team employed a technique known as optogenetics to selectively stimulate the prefrontal projections to paraventricular thalamus. The researchers also used chemogenetics in their study. While optogenetics enables researchers to stimulate particular neurons in freely moving animals with pulses of light, chemogenetics allows non-invasive chemical control over cell populations. By employing both of these techniques, the researchers were able to quickly increase social interaction in these mice once light pulses or drugs were administered to them.

"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.

Given that social behavior deficits are a common dimension of many neurodevelopmental and psychiatric disorders, such as autism and schizophrenia, identification of these specific prefrontal neurons will point toward therapeutic targets for the improvement of social behavior deficits shared across a range of psychiatric disorders. The circuits identified in this study could potentially be modulated using techniques like transcranial magnetic stimulation and/or transcranial direct current stimulation.

https://www.sciencedaily.com/releases/2020/08/200831112345.htm

Impact of children's loneliness today could manifest in depression for years to come

May 31, 2020

Science Daily/University of Bath

Children and adolescents are likely to experience high rates of depression and anxiety long after current lockdown and social isolation ends and clinical services need to be prepared for a future spike in demand, according to the authors of a new rapid review into the long-term mental health effects of lockdown.

The research, which draws on over 60 pre-existing, peer-reviewed studies into topics spanning isolation, loneliness and mental health for young people aged 4 -- 21, is published today (Monday 1 June 2020) in the Journal of the American Academy of Child and Adolescent Psychiatry.

According to the review, young people who are lonely might be as much as three times more likely to develop depression in the future, and that the impact of loneliness on mental health could last for at least 9 years.

The studies highlight an association between loneliness and an increased risk of mental health problems for young people. There is also evidence that duration of loneliness may be more important than the intensity of loneliness in increasing the risk of future depression among young people.

This, say the authors, should act as a warning to policymakers of the expected rise in demand for mental health services from young people and young adults in the years to come -- both here in the UK and around the world.

Dr Maria Loades, clinical psychologist from the Department of Psychology at the University of Bath who led the work, explained: "From our analysis, it is clear there are strong associations between loneliness and depression in young people, both in the immediate and the longer-term. We know this effect can sometimes be lagged, meaning it can take up to 10 years to really understand the scale of the mental health impact the covid-19 crisis has created."

For teachers and policymakers currently preparing for a phased re-start of schools in the UK, scheduled from today, Monday 1 June, Dr Loades suggests the research could have important implications for how this process is managed too.

She adds: "There is evidence that it's the duration of loneliness as opposed to the intensity which seems to have the biggest impact on depression rates in young people. This means that returning to some degree of normality as soon as possible is of course important. However, how this process is managed matters when it comes to shaping young people's feelings and experiences about this period.

"For our youngest and their return to school from this week, we need to prioritise the importance of play in helping them to reconnect with friends and adjust following this intense period of isolation."

Members of the review team were also involved in a recent open letter to UK Education Secretary, Gavin Williamson MP, focusing on support for children's social and emotional wellbeing during and after lockdown. In their letter they suggested that:

- The easing of lockdown restrictions should be done in a way that provides all children with the time and opportunity to play with peers, in and outside of school, and even while social distancing measures remain in place;

- Schools should be appropriately resourced and given clear guidance on how to support children's emotional wellbeing during the transition period as schools reopen and that play -- rather than academic progress -- should be the priority during this time;

- The social and emotional benefits of play and interaction with peers must be clearly communicated, alongside guidance on the objective risks to children.

Acknowledging the trade-offs that need to be struck in terms of restarting the economy and reducing educational disparities, their letter to the Education Secretary concludes: 'Poor emotional health in children leads to long term mental health problems, poorer educational attainment and has a considerable economic burden.'

https://www.sciencedaily.com/releases/2020/05/200531200333.htm