Cognitive behaviour therapy and inflammation: A systematic review of its relationship and the potential implications for the treatment of depression

There is increasing evidence for a low-grade inflammation to contribute to the pathophysiology of depressive disorders and to characterize a subpopulation of depressed subjects. Meta-analyses reported on elevated mediators of inflammation within depressive episodes, changes in levels during pharmacotherapies or even a predictive value for the outcome of pharmacological interventions. Thus, several agents with anti-inflammatory properties have been proposed to serve as antidepressants or antidepressive add-ons (Schmidt et al., 2016). The recent systematic review by Lopresti (2017) extends the range of interventions with potential influence on markers of inflammation to cognitive behaviour therapy (CBT) and puts emphasis on the relationship between CBT, depression and inflammation. In this review, answers to important questions were aimed to be given: (1) Does CBT reduce inflammatory agents? This was reported in 14 of the 23 studies included, while three investigations state the opposite and six report no changes during the intervention. Limiting the scope on major depression and depressive symptoms which, in other terms, merges diagnosis and syndrome away from categorical diagnoses towards a more dimensional approach, nine studies could be identified. Of these, the four studies on major depression indicate that CBT is related to reductions in inflammation markers. However, pooled estimates could not be provided due to the relevant heterogeneities between the studies. Varying study designs, the lack of control groups, intake of (various) psychotropic drugs and the range of markers from acute-phase proteins to cytokines to transcriptional factors add to the inconsistencies between studies. (2) Are anti-inflammatory properties of CBT associated with an improvement of the outcome in depression? Two out of three studies reported on correlations between changes in cytokine levels and depressive symptoms. This adds to previous findings that inflammatory markers could be a state marker of depression and symptom relief (Schmidt et al., 2016). Corresponding to results on pharmacotherapies (Uher et al., 2014), three studies further showed poorer treatment response to CBT in subjects with higher baseline levels of inflammatory mediators. One may debate that in cases of high cytokine levels, the early escalation of both psycho- and pharmacotherapy could help preventing current trial-and-error approaches. Lopresti provides potential mechanisms relevant for a positive relationship between the course of CBT and inflammatory markers, such as improvement in sleep, learning of relaxation practices, improvement in metabolic parameters as well as the initiation of a more positive and health-related lifestyle. Adding to these, another factor could be the increase in physical activities during the CBT intervention. Depressed and non-depressed subjects with low physical activity show higher cytokine levels than subjects with higher physical activity (Schmidt et al., 2014). Euteneuer et al. (2017) recently reported that anti-inflammatory interleukin (IL)-10 increases in depressed patients receiving CBT with emphasis on exercise compared to CBT with low-energy activities and the waiting list control group. This raises the question whether the effects of CBT on cytokines are predominantly mediated by the behavioural activation rather than cognitive therapy. If so, could patients preferably benefit from stand-alone exercise programmes than CBT, keeping the higher availability and lower costs in mind?

What are potential clinical benefits of the findings presented? CBT could be opted as a further anti-inflammatory and more personalized therapeutic approach in major depression, applied depending on the degree of inflammation. Separate from effects on depression, CBT could positively affect cardiovascular diseases (CVD) via a downregulation of inflammation. This could extend the indication of CBT to somatic disorders and could move the outcome criteria for CBT to somatic parameters. Furthermore, regular exercise programmes are important components in the antidepressive treatment which are probably mediated via a modulation of inflammation. Intensified research to advance the question if and how CBT is related to inflammation is needed and should be performed in the near future. The data presented by Lopresti provide several good arguments to do so.

See Key Review by Lopresti 51: 565–582.