Social Rejection Impacts the Brain and Body

Vladimir Maletic, MD, MS, clinical professor of neuropsychiatry and behavioral science, University of South Carolina School of Medicine, Greenville, who recently co-presented a session titled "Love and Loneliness in the Time of COVID-19: Clinical Relevance of Relationships" at Psych Congress 2021 in San Antonio, Texas, explores the effects of social relationships, including loneliness and isolation, on the brain and the body.

In the upcoming part 2, Dr Maletic, who is also Psych Congress Network’s attention-deficit/hyperactivity disorder (ADHD) section editor, interviews Bernadette DeMuri-Maletic, MD, medical director of Associated Mental Health Consultants and the TMS center of Wisconsin, Milwaukee, about the impact of loneliness on general health, including disease development, and the brain-body impact of marital connections.

Read the transcript:

Dr Bernadette DeMuri-Maletic:  I'm Bernadette DeMuri-Maletic. I'm a psychiatrist and director of the TMS Center of Wisconsin. I'm on clinical faculty at the Medical College of Wisconsin in Milwaukee.

Dr Vladimir Maletic:  My name is Vladimir Maletic. I'm [an] adult, and child, and adolescent psychiatrist. I have clinical affiliation with the University of South Carolina School of Medicine in Greenville, South Carolina.

In addition to that, I spend a lot of time treating my patients suffering from difficult-to-treat mood disorders. I have [a] special interest in neurobiology of major mood disorders but also ADHD and sleep and wakefulness.

Thank you very much for joining us for this conversation. Bernie, you had some questions for me.

Bernadette:  I did, Vlad. What do we know about what goes on in the brain in close social relationships and what goes on when they end?

Vladimir:  Those are both great questions. There have been imaging studies trying to assess what happens in some of our most intense interpersonal relationships, namely in romantic relationships. Here's what happens. The more passionate the relationship is and the more we find our partner attractive to us, it activates reward circuitry in the brain.

These reward centers such as ventral striatum, such as parts of ventromedial prefrontal cortex seem to have a greater level of activity in individuals when they're thinking about their romantic partners.

There's something else that's interesting. Aside from increased signaling in these reward areas in the brain, the longer the romantic relationship lasts, the more it appears that we are ruminating and thinking about our partners.

Imaging studies have made a correlation between the duration of [a] passionate relationship and activity in so‑called default-mode network area of the brain, which does include precuneus. They have found more intense signal[s] in individuals who have been in a romantic relationship for [an] extended period, which does bode well for long relationships.

It's really interesting. It is a very similar pattern, oddly enough, that we see individuals who have substance-use issues in that reward areas are activated in response to passionate feelings and attraction to our partner but also the duration of romantic relationship seems to support increased activity in default-mode network.

I wouldn't say we're obsessed, but we're preoccupied with the person that we may be romantically involved with. You asked a very good question. What happens when a romantic relationship ends? There was a study. Frankly, to a degree, it had a disturbing outcome. This is how the study was construed. On their left hand, participants in the study had a thermode.

Thermode was providing a heat stimulus, which would be ramped up to the point where it would be painful. The individuals who participated in the study were selected because they had a very passionate romantic relationship end in recent past. How do we know that it was passionate? It was graded. Only individuals who had intensity of passion above 50% were included in the study.

Unbeknownst to the participants of the study, investigators obtained photos of their ex-partners who ended the relationship. Now they are in a scanner. In the first phase of the experiment, they're getting heat administered through thermodes. 100% was very painful stimulus, unbearable.

They adjusted it so stimulus would be somewhere between 40-70%. They're getting the heat stimulus. Their brain is being imaged. We see increase in activity in certain parts of the brain in response to heat. The parts of the brain that were engaged are the ones that are commonly thought of as pain matrix.

There was a change in thalamus. There was a change in [the] dorsal anterior cingulate and, not surprisingly, a change in some of the sensory cortex that reflects duration of the pain, intensity of the pain, and localization of the pain. That is the first phase of the experiment.

In the next phase of [the] experiment, while they're still in the scanner, there's a screen. All of [a] sudden, picture of their romantic partner who ended the relationship flashes. This was unanticipated. Participants are taken aback.

Guess what the imaging study shows. All the areas in the brain that register pain, so-called the pain matrix, were engaged when they were looking at a picture of their ex-romantic partner who ended this passionate relationship. In some ways, ending a romantic relationship is very similar to enduring physical pain. There was some difference in intensity, but [the] brain did not differentiate between these 2.

Something else that is quite intriguing, in terms of social pain associated with being isolated and lonely, in one of the studies that compared placebo, which was potassium and acetaminophen, a common analgesic, found that administration of common analgesic, oddly enough, decreased social pain.

Indeed, our brain does process a romantic relationship and it looks as if it's a rewarding stimulus. All this pleasure, feel-good circuitry is involved. Default-mode network associated with ruminative thoughts and preoccupation is also engaged. All good things, elaboration of that good feeling.

On the other hand, when there is abrupt interruption in this passionate romantic relationship, it is akin to experiencing physical pain.

Bernadette:  Interesting. Vlad, we know that romantic or other relationships have an impact on the brain. How about on the body?

Vladimir:  Very much so. We need to take into account that human beings have evolved as social beings. If we think about how things were millennia ago, in order to have nurturance and closeness, even heat, if we were close to other human beings, we fared better. If there was a danger looming from predators on another tribe, if we were a group, we did better.

When it came to gathering and hunting, if we acted as a group, we did better. Through selection, having social connectedness has translated as a safety signal. Therefore, if we are socially disconnected, if we are rejected, or if we are lonely, it's not only that our brain interprets this as a threat-to-danger signal, we see all the reverberations in the body.

If we are lonely, if we are isolated, if we are rejected, there is a change in autonomic function, sympathetic tone is higher, parasympathetic tone is lower. There is [an] activation of hypothalamic-pituitary-adrenal activity, therefore, stress hormones are being released in the body. Finally, there is activation of inflammatory response.

One might say, "Well, what sense does it make that loneliness activates all these bodily manifestations?" We have to keep in mind evolution. Being alone, especially alone in the dark, imagine what this was like tens of thousands of years ago. That was a dangerous scenario. An increase in autonomic activity causes [the] redistribution of norepinephrine.

We have more norepinephrine in our brain, in our heart, in our muscles. We're probably not sleeping well that night when we are alone in the darkness in the cave, which may have helped preserve individuals, because they are susceptible to any kind of danger and attack. If this danger comes their way, having increased corticosteroids provides source of energy.

Finally, if there is some kind of a scrape and their bodily integrity is disrupted, having [a] ramped-up immune system may help heal and survive. We have to keep it in context. These systems that have evolved to enhance the likelihood of survival of [the] human species, interestingly enough, now become activated when we're alone or when we are rejected.

Vladimir Maletic, MD, MS, is a clinical professor of psychiatry and behavioral science at the University of South Carolina School of Medicine in Greenville, and a consulting associate in the Division of Child and Adolescent Psychiatry, Department of Psychiatry, at Duke University in Durham, North Carolina. Dr Maletic received his medical degree in 1981 and his master’s degree in neurobiology in 1985, both from the University of Belgrade in Yugoslavia. He went on to complete a residency in psychiatry at the Medical College of Wisconsin in Milwaukee, followed by a residency in child and adolescent psychiatry at Duke University.
Bernadette DeMuri-Maletic, MD, received her medical degree from the Medical College of Wisconsin. She completed residencies in both Psychiatry and Neurology at the Medical College of Wisconsin Affiliated Hospitals. Dr DeMuri is the medical director of associated mental health consultants and The TMS center of Wisconsin, both located in Milwaukee. She is an assistant clinical professor at the Medical College of Wisconsin. Dr DeMuri has a special interest in the treatment of mood disorders including treatment-resistant depression.