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Uncovering the Relationship Between Loneliness and Poor Health Outcomes

In This Article

  • Loneliness and social isolation have been growing concerns since even before the COVID-19 pandemic
  • This epidemic of loneliness and social isolation has broad public health implications, including links to poor cardiometabolic health and premature death
  • In an ongoing study, Massachusetts General Hospital researchers identified a potential neural marker of loneliness, which could help shed light on the effects of loneliness on the body and how to reverse those effects

Ongoing work by Daphne Holt, MD, PhD, a psychiatrist at Massachusetts General Hospital and a faculty member at the Martinos Center for Biomedical Imaging, and colleagues could help tackle the worsening epidemic of loneliness and social isolation in the general population.

Public health experts and others called attention to this epidemic even before the COVID-19 pandemic. At the same time, researchers have shown that loneliness and isolation are particularly common in those suffering from serious mental illnesses, including psychotic disorders, affecting approximately 80% of people with these conditions.

This societal problem has broad public health implications. A growing body of literature has linked loneliness and isolation to poor cardiometabolic health and premature death. Little is known, though, about the brain mechanisms underlying this relationship and how they might vary across different groups of people.

Clues have emerged to help connect the dots. For example, studies have shown that certain cognitive and behavioral biases are associated with loneliness, including a bias towards social mistrust and a related tendency to maintain a greater physical distance ("personal space") from others. (In 2021, Dr. Holt and the Martinos Center's Roger Tootell, PhD, reported research exploring the potential impact of social distancing on personal space requirements, which often serve as a marker of social functioning.)

Now, Dr. Holt and colleagues, including Faye McKenna, PhD, Louis Vinke, PhD, and Mona Avanaki, MD, have leveraged these biases to help identify changes in brain functioning associated with loneliness and social isolation—in other words, neural markers of loneliness—in people with and without psychotic disorders.

They did this by scanning subjects with functional MRI while showing them videos with either faces approaching them and appearing to violate personal space boundaries—thus triggering the sensitivity to a social threat that has been associated with loneliness—or faces moving away from them, signaling social withdrawal.

In fact, the study revealed an association between loneliness and a greater response to the withdrawing faces in the hippocampus and a related network of subcortical brain regions involved in emotion and homeostatic regulation. This pattern of responses was similar across the psychotic disorder and healthy control groups, suggesting that it may represent a marker of loneliness.

"Understanding how the brain responds when a person's social needs are not being met gives us an objective way to measure and monitor this type of deficit," says Dr. Holt, "which will help us understand the effects of loneliness on the body and how to reverse those effects."

In ongoing work, the researchers are testing whether the potential marker of loneliness is linked to some of the known biological effects of loneliness (including cardiometabolic and inflammatory dysregulation), and whether these effects play a role in the poor health outcomes and earlier mortality associated with psychotic disorders and loneliness across populations.

Learn more about the Martinos Center for Biomedical Imaging

Learn more about research in the Department of Radiology

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In this Q&A, Daphne J. Holt, MD, PhD, teaches skills for dealing with the overwhelming stress on health care workers during the pandemic and discusses how learning resiliency through online training can help them manage their mental health during this stressful time.


Researchers at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital are using virtual reality to study how 'personal space' requirements have changed as a result of social distancing during the COVID-19 pandemic—and the possible impact of these changes on social functioning.