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

New research highlights increased loneliness in over-70s during COVID-19 pandemic

July 15, 2020

Science Daily/Trinity College Dublin

A joint report published by researchers at the Irish Longitudinal Study on Ageing (TILDA) and ALONE examines issues of loneliness and social isolation in older adults. The report offers fresh insight into the experiences of those over 70 who were advised to 'cocoon' as part of public health measures to curtail the spread of the COVID-19 virus. New data from ALONE which documents increased feelings of loneliness, anxiety and isolation in older adults throughout the pandemic, is compared with experiences of loneliness and isolation in older adults before the COVID-19 outbreak.

Previous research into this area has shown that strong social ties may protect people from emotional distress, cognitive decline, and physical disability, while loneliness and social isolation can cause harm to physical and psychological wellbeing. Both loneliness and social isolation have been strongly associated with poorer quality of life and other measures of well-being.

The TILDA study offers unique insights into the health, habits and experiences of older adults living in Ireland through its longitudinal research, examining a variety of key areas that affect older adults such as physical and mental health as well as economic and social factors. Research from TILDA highlights the prevalence of loneliness and social isolation in its nationally representative survey of participants which gives clear insight into the experiences of older people.

What does TILDA's research show prior to the pandemic?

• Over 70% of TILDA participants reported that they never or rarely feel lonely; less than 25% feel lonely some of the time while just 5% reported feeling lonely often.

• Of those living alone, 31% are rarely lonely, 32% sometimes lonely and 37% often lonely.

• Of those living with others, 49% are least lonely, 30% sometimes and 21% often lonely.

• Researchers point out that most older adults are not often lonely and appear quite resilient, while data from ALONE's helpline suggest that the COVID-19 pandemic has taken a toll on older people.

The rise of loneliness in a pandemic

Measures introduced to curb the spread of the COVID-19 virus, including physical distancing, and self-isolation particularly affected those over 70 who were 'cocooning'; disrupting daily routines and social interactions with friends and family. Following the outbreak of the virus, ALONE's Support and Telephone Befriending service continued remotely with volunteers calling and sending regular texts to older people with health and well-being tips and practical supports. Almost 500 smartphones were distributed to older adults with limited means of social interaction. Following an increase in calls for support, ALONE established a dedicated phoneline to provide help and services to vulnerable older adults who may have needed them. Report data from ALONE highlights increased feelings of loneliness and isolation amongst older people during the COVID-19 pandemic.

What does ALONE's research show?

• The ALONE national support line has received 26,174 calls during the period: March 9th to July 5th, 2020.

• 55% of callers were from the over 70s, the cohort advised to 'cocoon'.

• 75% of callers to the helpline were living alone.

• There has been an increase in callers who are putting off medical treatment or examination, including after falls.

• ALONE has seen a rise in callers reporting negative emotions, including suicidal ideation during the pandemic.

• Callers have most often requested support for their physical health, befriending, and emotional and mental health needs.

The data highlights that public health measures such as social distancing and cocooning to curb the spread of the virus has increased levels of loneliness and social isolation in older people. This may have a negative effect on the well-being of older adults and suggests that public policies should be developed to ensure that these issues are addressed. Researchers suspect that current physical distancing and social isolation measures will be most keenly felt by those who rely on community or church-based social participation and engagement.

A future research project led by TILDA in collaboration with ALONE will investigate and document the impact of the COVID-19 pandemic on the health and general well-being of older adults.

Professor Rose Anne Kenny, Principal Investigator of TILDA said:

''This collaborative report between ALONE and TILDA offers a unique perspective into how older adults have been affected by the COVID-19 pandemic. TILDA research shows that most older adults are not often lonely and highlights the resilience of older adults as they adapt to an ever-changing world. The world has witnessed how older adults have been disproportionately affected by the pandemic. ALONE's research provides front- line evidence that shows the true toll public health measures have had on older people with increased feelings of loneliness, anxiety and isolation. The impact of the pandemic is now being studied in the TILDA cohort and will be reported later this year. This will more precisely inform the impact of COVID-19 on loneliness and social isolation, and areas for policy intervention.''

Sean Moynihan, Chief Executive Officer of ALONE said:

''ALONE's coordinated National Response to the COVID-19 pandemic allowed us to respond with immediacy to the concerns newly emerging, and existing issues being elevated from older people. We worked to keep all our services operative through adaptation of their structures. The presence of this virus in society has further solidified existing issues while further alienating some older people, as we have seen extensive increases in loneliness through the isolation experienced from cocooning. We established a loneliness taskforce to ensure we were putting provisions in place to safeguard older people, presently, and into the future. Society needs to understand that loneliness can happen to anyone and can damage both your physical and mental health. It is distressing and we want to work towards breaking down this stigma. As Ireland's ageing population continues to develop, we must remember that there are several thousands of older people behind every percentage."

https://www.sciencedaily.com/releases/2020/07/200715111451.htm