Loneliness, Social Isolation, and Major Depressive Disorder

While psychotherapy, psychosocial treatments, and psychopharmacology have been the standard treatment for major depressive disorder (MDD), social ties also play a significant role in determining whether or not patients can achieve remission.

Ahead of his session at Psych Congress 2023, “Social Relationships: Their Key Role in Etiology and Treatment of Psychiatric Disorders,” Vladimir Maletic, MD, MS, clinical professor of psychiatry at the University of South Carolina School of Medicine in Greenville, South Carolina, and Psych Congress Network ADHD section editor, discussed recent research that highlights how social isolation can contribute to and prolong MDD.

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Read the Transcript: 

Vlad Maletic, MD, MS: My name is Vlad Maletic. I am clinical professor of psychiatry at the USC School of Medicine in Greenville, South Carolina, as well as a member of program committee at Psych Congress.

There are multiple psychiatric conditions and phenomena that are associated with loneliness and social isolation. So being lonely is associated with significantly increased risk of developing major depressive disorder. It is associated with increased risk of developing anxiety disorders. There is a bidirectional relationship between loneliness and insomnia. Oddly enough, people who do not sleep well are more likely to be lonely. It is possible that major depressive disorder is a mediating variable in this equation. Loneliness is associated with increased risk of substance use disorders. Loneliness is also associated with greater risk of cognitive decline. So again, very important outcomes are associated with loneliness. In terms of how might this association be mediated, we have assembled a pretty convincing evidence that loneliness is associated with similar type of functional connectedness in the brain as response to threat and danger signals. So being lonely, in human beings who have evolved to be social creatures, so to say, is something that is felt.

Again, this is not a product of conscious thought, but it is experienced by us as being in a dangerous and threatening situation. If you think about it, these defensive mechanisms have evolved millennia ago. For human beings to be all alone in the cave in the past was not a good scenario. Therefore, there is a pattern of brain activity that is different and consistent with the brain activity in chronically stressful situations, mood disorders, and anxiety disorders. Manifestations of loneliness in the body are also very similar to many psychiatric conditions. So individuals who are lonely have alterations in their hypothalamic pituitary adrenal axis activity. Stress hormones tend to be higher. Autonomic balance is shifted from parasympathetic to sympathetic, again, something that is seen in threatening and dangerous situation, maybe not to the same magnitude, but the same type of change. In addition to that, loneliness is associated with increased inflammatory tone.

All of those may translate into increased cardiometabolic risk, and they may also be associated with some of these physical manifestations of loneliness and impact on longevity. What do we know about loneliness and mood disorders, specifically major depressive disorder? In the recent years, we've been able to quantify genetic risk for major depressive disorder. There are about 120 genes, which all have minor but additive impact on the risk of developing depression. So each one of those risk genes checks a box, and we can count them all up. The study that I'm referring to compared a large sample of individuals, and we're talking about two categories of individuals. One, these are medical interns exposed to a lot of stress. Two, are people who are recently widowed. And they looked at the relationship between polygenic risk scores, so genetic risk for developing major depressive disorder, and loneliness. What they found is that there's a robust interaction. The more lonely one is and the greater genetic risk one has, the greater depression severity scores on standardized scales.

So again, something that is a very important finding. There's interaction between loneliness and the biological basis for MDD. The other study is equally, if not more, astounding. It is pulled analysis. The sample included about 800 individuals who suffer from major depressive disorder and a comparable number of healthy controls, and they looked at what differentiates individuals who have depression versus healthy controls. White matter volume, gray matter volume, functional connectivity in the brain, polygenic risk scores, genetic risk for a depression, they were all left in the dust. The biggest differentiators between people who are depressed and the ones who are not is in social support. Those lacking social support had much greater risk. In the same neighborhood, same impact, childhood maltreatment. So again, these are the two key differentiating factors, yet they do not receive the attention they deserve in the psychiatric community.

Lastly, why do we care? Well, combination of psychotherapy, other psychosocial treatments, and pharmacology has been a standard of treatment of major depressive disorder. But are you aware that individuals who are lonely have over 30% reduction in likelihood of achieving remission within 3 to 4 month treatment? So we need to address this issue, again, that does not receive the attention that it deserves.

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.