How Our Immune System Drives Social Preferences

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Most of us enjoy, if not even prefer, spending time with others rather than spending all of our free time in social isolation. Some studies even suggest that social connectivity plays a significant role in our overall health and well-being (1, 2). So what is it then that drives this preference to be with others, and similarly, what contributes to the social indifference or even social aversion seen in some neurologic disorders like autism spectrum disorder and schizophrenia? It looks like, at least in part, it’s pathogenic microbes like bacteria and viruses.

Exciting new research suggests that our immune system may drive our preference for social interactions, and these new findings raise fundamental questions about human behavior. There’s a quote that’s been circulated widely among researchers studying the interactions between microorganisms and humans that I read in an interview with Justin and Erica Sonnenburg: “Humans are elaborate culturing vessels that have evolved to propagate and pass on these micro-organisms,” and this new research, published last month, suggests that even our behavior may have evolved as a means of supporting the spread of microbes.

There are a few reasons this research is so significant.

The brain is directly connected to our immune system

The first huge finding to understand is that our brain is intimately connected to our immune system. This may not seem like a novel idea to many people since we intuitively know that we generally feel lousy all around when we’re sick. But up until about a year ago, the widely held notion taught to all medical students was that the brain was a protected organ, essentially separated from the rest of the body by the blood-brain barrier—a fortress of tightly connected cells surrounding the brain’s vessels that allows selective passage of nutrients and protects the brain from an onslaught of invading microbes or overwhelming immune response. The brain had thus been considered “immunologically privileged.”

Neurologic disorders including autism and schizophrenia are directly linked to the immune system.

In addition to the protective blood-brain barrier, the brain was thought to be lacking lymphatic vessels, layering on additional isolation from our immune system. Lymphatic vessels are the third system of vessels, along with arteries and veins, that support the flow of fluid from cells into the bloodstream. Lymphatic vessels importantly drain our lymph nodes, structures situated along these vascular networks that store immune cells. (You can often feel enlarged and sometimes tender lymph nodes when you have a cold or other infection—this is a sign that your immune system is working to fight an infection.)

But last year, lymphatic vessels in the meninges—structures surrounding the central nervous system and containing the reservoir of cerebrospinal fluid—were identified (3). This discovery created a paradigm shift in how we can understand and explore the interaction between the immune system and the brain. It also opened up a whole new avenue from which to explore the interaction between immune dysfunction and disorders like multiple sclerosis, Alzheimer’s disease, schizophrenia, and autism spectrum disorder.

As the article, published in Nature in June 2015, notes, “The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune dysfunction.” Or put more simply, we now need to reconsider how the immune system affects our brains because our brain is not as isolated and protected as was once believed.

So that’s the first really cool and important discovery to understand here: Our brain and immune system have a direct link.

Immune deficiency and a lack of interest in socializing are linked

Next, researchers set out to better understand this interaction. An article published last month clarifies one pathway in which our immune system’s response to pathogens may drive our normal social behavior (4).

Normal social behavior is important for a number of reasons, and in humans, this includes a benefit for our mental health. Social dysfunction is seen in several neurologic and neuropsychiatric conditions including autism spectrum disorder, schizophrenia, and certain types of dementia. Interestingly, these conditions are also associated with immune dysfunction, specifically with cells of the immune system called T cells (5, 6, 7).

Researchers took mice deficient in T cells and showed that these mice, in contrast with normal, or “wild-type,” mice, showed no preference for social interaction over an inanimate object (yes, these are mice, but I think we can still agree this is social dysfunction). Then, these T cell-deficient mice were injected with normal immune cells, specifically with lymphocytes to supply the T cells they were previously missing. After a few weeks, allowing the immune system to respond to this lymphocyte injection, these mice showed a preference for normal social behavior. So the social dysfunction was reversed by restoring immune balance.

Additionally, there is a type of imaging called functional MRI that can assess brain activity (not just structural information, but actual measures of tissue activity). This type of functional imaging has shown hyperconnectivity in certain regions of the brain in people with autism spectrum disorder (8). This functional imaging was also performed in mice and showed a similar pattern of hyperconnectivity in the mice lacking a normal immune system. But again, once these mice were injected with lymphocytes allowing the immune system to normalize, the brain imaging also normalized.

Brain imaging in mice with immune dysfunction has similar abnormalities to brain imaging in children with autism spectrum disorder. The brain imaging normalized after these mice were injected with lymphocytes restoring normal immune function.

This is the second key point: Immune deficiency in mice was associated with a lack of interest in social interaction, but correcting this immune imbalance led to normal social preferences.

Next, researchers set out to discover how the T cells were affecting behavior, and interferon-gamma (IFN-𝛾) was identified as playing a major role in affecting this social behavior. IFN-𝛾 is an important compound, more generally called a cytokine, in the immune system (specifically in the adaptive immune response and produced largely by T cells). This cytokine, IFN-𝛾, is produced when our immune system responds to a pathogen, like a bacteria or virus. So, IFN-𝛾 supports our normal social behavior, and (at least in mice) low IFN-𝛾 is associated with social dysfunction.

This immune molecule, IFN-𝛾, seems to be critical for social behavior.

What does this mean for you?

There’s still much to understand, but most of us are affected in one way or another by someone with autism, dementia, or schizophrenia, and this research shows us that the immune system, and by extension the pathogens that cause an immune response, may actually drive brain function. These new findings open novel pathways for additional research into understanding and treating these complex conditions.

I want to make an important point here that I don’t think autism, schizophrenia, or any of these neurologic disorders will be corrected by one strategy, and at the same time, I do think we need to pay careful attention to the immune system in these conditions. This may mean removing any toxins or chronic infections that could be contributing to an immune imbalance, but there is still much to learn.

And, I think this information provides yet another reason to keep our immune system balanced and functioning well (as if we needed another)!

About Amy:  Amy Nett, MD, graduated from Georgetown University School of Medicine in 2007.  She subsequently completed a year of internal medicine training at Santa Barbara Cottage Hospital, followed by five years of specialty training in radiology at Stanford University Hospital, with additional subspecialty training in pediatric radiology.

Along the course of her medical training and working through her own personal health issues, she found her passion for functional medicine, and began training with Chris in June of 2014.  She subsequently joined the California Center for Functional Medicine to work with patients through a functional medicine approach, working to identify and treat the root causes of illness.  Similar to Chris, she uses nutritional therapy, herbal medicine, supplements, stress management, detoxification and lifestyle changes to restore proper function and improve health.

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