A comprehensive analysis of 56 randomized controlled studies has concluded that psychosocial interventions—and especially cognitive behavioral therapy (CBT)—are associated with improvements in the functioning of the human immune system.

The finding, published in JAMA Psychiatry, could be of considerable importance, given the large body of research that has implicated the immune system in a wide variety of mental and physical health problems. Mortality data from 195 nations covering the period 1980 to 2015 has indicated that over 50% of all deaths are attributable to inflammation-related conditions, such as heart disease, neurodegenerative disorders, and stroke. Inflammation is caused by immune-system activation. Although it is generally helpful in the short run, chronic inflammation contributes to increased risk of several physical illnesses in addition to mental health problems, including anxiety disorders, depression, and schizophrenia.

A team led by 2015 BBRF Young Investigator George Slavich, Ph.D., Director of the Laboratory for Stress Assessment and Research at the University of California, Los Angeles, wanted to better understand how therapeutic interventions that change social or behavioral processes affect the immune system. The idea for the study comes from a larger body of research, which has shown that different immune-system processes are influenced by social, neurocognitive, and behavioral factors. Among many things, this research has shown that life stress, negative emotions, and a lack of social support can affect health by influencing the function of the immune system.

Dr. Slavich and colleagues conducted a broad survey of the literature, winnowing a pool of 4,621 studies to only 56, involving 4,060 participants, which met a series of stringent criteria for their own “meta-analysis.” In a meta-analysis, the findings of previous studies are assessed in aggregate. To make the cut, the studies had to be randomized and placebo-controlled, meaning that neither participants nor researchers knew which participants were receiving an “active intervention” and which were receiving the equivalent of a placebo. Additionally, the included studies needed to have measured a variety of immune-system functions in all participants both before and after the active phase of the study.

The 56 selected studies tested a total of eight psychosocial interventions: behavior therapy, cognitive therapy, cognitive behavioral therapy (CBT), CBT plus another augmenting treatment; bereavement therapy, multiple or combined interventions, other forms of psychotherapy, and psychoeducation. Those receiving these treatments were tested for a total of seven immune system factors or biomarkers. Finally, the 56 included studies enabled Dr. Slavich’s team to measure what impact, if any, nine demographic or treatment-related factors had in potentially affecting the results: age, sex, type of intervention, length of intervention, disease state of the participants, if any, etc.

The first conclusion, once all the different datasets were analyzed: “Psychosocial interventions as a whole were significantly associated with enhanced immune system function,” Dr. Slavich’s team reported. The association was not skewed, for example, due to the great success of just a few studies; rather, it was “relatively consistent across studies.” And it met the mathematical test of statistical significance: across all the studies, there was 14.7% improvement in beneficial immune system function in participants who received the active therapy, as compared with control participants in these same studies. Similarly significant, the team said, was an 18% decrease in harmful immune system function over time—meaning, not just at the end of the active intervention but over a period of 6 months after treatment ended.

Importantly, of the eight psychosocial interventions assessed, only two were significantly associated with positive immune-system outcomes: CBT and CBT plus adjunctive therapies. Other findings: there was some evidence that group therapy or discussion might have more consistent positive impact on immune function. Also, of the seven types of immune markers monitored across the trials, only two seemed to be significantly impacted (for the better) by psychosocial interventions: levels or markers of pro-inflammatory molecules, called cytokines; and in overall immune cell “counts” in participants. Neither age nor sex nor length of intervention seemed to alter the main findings, the team reported.

The researchers compared the impact of psychosocial interventions overall, and CBT in particular, with medications that have been used to improve immune function in patients with a variety of illnesses. Assuming CBT involves about 10 weeks of once-weekly therapy sessions, the team estimated the cost of a typical course of therapy at about $1500; they noted that a medicine called infliximab to reduce inflammation in people with autoimmune disorder “is approximately $25,000 per patient per year.” Yet the amount of functional immune improvement with the medicine was about the same as that seen with CBT. “CBT may thus represent an affordable and relatively longer-lasting adjunctive treatment option for reducing inflammation-related disease risk,” the team wrote.

Dr. Slavich and colleagues called for future studies to search for the biological mechanisms that may be impacted by psychosocial therapies to generate positive immune-system effects, a topic not covered in the current study.