Cognitive-Behavioral Therapy a Standout for Better Immune Function

Michael Vlessides

June 11, 2020

Psychosocial interventions, particularly cognitive-behavioral therapy (CBT), are associated with enhanced immune system function, new research suggests.

Results of a systematic review and meta-analysis that included 56 randomized controlled trials and more than 4000 participants showed that over time, psychosocial interventions appeared to augment beneficial immune system function while concurrently decreasing harmful immune system function in comparison with control conditions.

"These associations were most reliable for cognitive-behavioral therapy and multiple or combined interventions and for studies that assessed proinflammatory cytokines or markers, which are key indicators of inflammation in the body," study investigator George M. Slavich, PhD, told Medscape Medical News.

"The analysis helps address the question of which types of psychosocial interventions are most consistently associated with changes in immune system function, under what conditions, and for whom. This knowledge could, in turn, be used to inform research efforts and public policy aimed at using psychosocial interventions to improve immune-related health outcomes," added Slavich, who is director of the Laboratory for Stress Assessment and Research, University of California, Los Angeles.

The study was published online June 3 in JAMA Psychiatry.

Link to Serious Physical, Mental Illnesses

There is substantial evidence that the immune system plays a role in a variety of mental and physical health problems. Such problems include anxiety disorders, depression, suicide, schizophrenia, cardiovascular disease, autoimmune disorders, and neurodegenerative diseases. It is has been recently suggested that more than half of all deaths worldwide are attributable to inflammation-related conditions.

Although pharmacologic interventions can play a role in addressing inflammation, they are not without drawbacks, most notably, cost and adverse side effects.

The World Health Organization, the National Academy of Medicine, the National Institutes of Health, and other groups have emphasized the importance of addressing global disease burden through psychosocial interventions when possible.

Such recommendations are supported by scientific evidence. Previous research has shown that immune system processes are influenced by a variety of social, neurocognitive, and behavioral factors.

Given such findings, researchers have examined the effects of interventions that reduce stress or bolster psychological resources on immune system function.

However, such research has yielded conflicting findings. Some studies show that psychosocial interventions clearly enhance immunity, whereas others do not.

In addition, questions remain regarding which types of interventions reliably improve immune system function, under what conditions, and for whom.

"Research has shown that psychological factors ― such as life stress, negative emotions, and social support ― are associated with changes in immune system function," Slavich noted.

"In addition, there is growing appreciation that immune system processes involved in inflammation may contribute to peoples' risk for several major mental and physical health problems, including anxiety disorders, depression, heart disease, and autoimmune and neurodegenerative disorders."

First Study of Its Kind

To shed light on these potential links, the researchers conducted what they believe is the first systematic review and meta-analysis of randomized clinical trials of the effects of psychosocial interventions on immune system outcomes.

As part of the review, Slavich and colleagues estimated the associations between eight psychosocial interventions and seven markers of immune system function.

The eight psychosocial interventions were behavior therapy, cognitive therapy, CBT, CBT plus additive treatment or mode of delivery, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation.

The seven immune outcomes that might be influenced by these interventions included proinflammatory cytokines and markers, anti-inflammatory cytokines, antibodies, immune cell counts, natural killer cell activity, viral load, and other immune outcomes.

The researchers also examined nine potential factors that might moderate the associations between psychosocial interventions and immune system function.

They searched a variety of databases for all relevant randomized controlled trials published through December 31, 2018. Studies were eligible for inclusion if they included a psychosocial intervention and immune outcome, as well as preintervention and postintervention immunologic assessments.

The researchers identified 4621 studies. Of these studies, 62 were eligible for inclusion; 56, which included 4060 patients, were included in the final meta-analysis.

Results showed that psychosocial interventions were associated with enhanced immune system function (P < .001). Interestingly, there was relatively low heterogeneity between studies in these effect sizes, which, the investigators say, indicates that the association was relatively consistent across studies and conditions.

The meta-analysis showed that individuals who were assigned to a psychosocial intervention condition demonstrated a 14.7% improvement (95% confidence interval [CI], 5.7% – 23.8%) in beneficial immune system function compared with their counterparts who were assigned to a control condition.

Similarly, participants who received psychosocial interventions demonstrated an 18.0% decrease (95% CI, 7.2% – 28.8%) in harmful immune system function over time.

A Standout

Regarding the effect of the type of intervention on the association, only CBT (31 studies; P < .001) and multiple or combined interventions (seven studies; P = .01) were significantly associated with changes in immune system outcomes.

The analysis also found that interventions that included a group component were more consistently associated with enhanced immune function than were those that did not include a group component. Nevertheless, this difference did not reach statistical significance (P = .06).

Contrary to the researchers' expectations, the analysis also revealed that intervention length did not moderate the association between psychosocial interventions and immune system function (P = .93).

With respect to the type of immune marker studied, the meta-analysis found that psychosocial interventions had significantly different associations with the various immune markers studied. Of the seven immune outcomes investigated, only proinflammatory cytokine or marker levels (33 studies; P < .001) and immune cell counts (27 studies; P < .001) were significantly associated with the psychosocial interventions examined.

The associations between psychosocial intervention and immune system function persisted for at least 6 months following treatment and were robust across age, sex, and intervention duration.

These results suggest that psychosocial interventions ― particularly CBT and multiple or combined psychotherapeutic modalities ― may play an important role in improving immune-related health outcomes.

Such interventions may not only be effective, they may also prove to be affordable alternatives to current therapeutic options. The mean length of a CBT intervention in the meta-analysis was 10.4 weeks, which the investigators equated with a total cost of $1560 per patient.

"By comparison, the cost of using infliximab to reduce inflammation in persons with an autoimmune disorder is approximately $25,000 per patient per year," they write.

"The results suggest the possibility that psychotherapy may be helpful for reducing inflammation and improving immune-related health in certain circumstances," Slavich concluded. "However, the studies that we examined differed in terms of their quality, and we did not examine health outcomes in the present investigation.

"Therefore, more research needs to be done to determine how the present findings might be translated into treatment options or public policy."

A Path to Better Health

In an accompanying editorial, Veronika Engert, PhD, Joshua A. Grant, PhD, and Bernhard Strauss, PhD, note that although infectious disease was once the primary cause of death in society, it has been supplanted by other complex and chronic illnesses, which often do not follow simple cause-and-effect associations.

"Rather," they write, "these illnesses develop from a complex milieu of biological, psychological, and social factors that may also influence the disease progress and its prognosis. Against this backdrop, the meta-analysis by Shields and colleagues is an important confirmation of the biopsychosocial model."

The editorialists explain that recent psychophysiological, neurobiological, and epigenetic research offers a glimpse into the relationship between psychological and social factors in pathogenesis. Nevertheless, the authors note that a comprehensive examination of the potential effects of psychosocial interventions on immune parameters in various physical health conditions has been lacking.

"The evidence provided by Shields et al is exactly what is needed to more fully shift treatment from an illness-centered to a patient-centered approach," they write. "To that end, this meta-analysis may serve as a guide for policy makers aiming to improve immune-associated health."

The research was supported by a Society in Science-Branco Weiss Fellowship, Brain and Behavior Research, and the National Institutes of Health. Slavich, Engert, Grant, and Strauss have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online June 3, 2020. Abstract, Editorial

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