Range of Inflammatory Biomarkers Associated With Depressive Symptoms
Research published recently in Depression & Anxiety confirmed a previously reported link between systemic inflammation, altered appetite, and fatigue. It also examined inflammatory markers other than the commonly used c-reactive protein (CRP), and suggests new targets for treating atypical depression.
Here, lead author Alessandro Gialluisi, MSc, PhD, of IRCCS Neuromed, Pozzilli, Italy, describes the research group’s findings, possible clinical applications, and directions for future research.
What led you and your colleagues to conduct this research?
A relationship between depression and circulating inflammation has been hypothesized and supported by some studies in recent years. However, some aspects of this link remain largely unexplored, such as the relationship between specific depressive symptoms and different inflammatory markers. A handful of studies published so far suggest that somatic (or neurovegetative) depressive symptoms such as altered sleep, fatigue/low energy, and eating behavior may be more strongly associated with inflammation as compared to cognitive (or psychological) symptoms like low mood, inability to experience pleasure, self-estimate, and suicidality. However, these observations were often made by measuring few plasmatic inflammatory markers such as c-reactive protein (CRP) and interleukin 6 (IL-6), while other important cellular mediators of inflammatory response, such as leukocytes, were fairly neglected. This prompted us to investigate this relationship more in detail.
Please briefly describe your study and its findings.
We investigated associations between specific self-reported depressive symptoms and systemic inflammation in the Moli-sani study, involving a large population cohort of Italian adults living in the Molise region (N = 13,301; age > 35 years). To do so, we used the INFLA-score—a global index based on 4 circulating biomarkers: CRP levels, blood platelet count, total leukocyte count, and granulocyte-to-lymphocyte ratio—capturing both plasmatic and cellular circulating inflammation.
We observed a positive association between the altered appetite/eating symptom with INFLA-score—the latter being driven mainly by CRP and leukocyte count—and between tiredness/low energy and granulocyte-to-lymphocyte ratio. These associations remained stable even taking into account the use of antidepressants, main chronic conditions, and lifestyle factors, while they were notably attenuated by obesity, in the case of appetite.
Were any of the outcomes particularly surprising?
While we provided support to the association of low-grade inflammation with altered appetite, and more in general with neurovegetative symptoms of depression, it was certainly surprising to observe that this evidence extended to cellular components of inflammation, such as total leukocytes (with altered appetite) or granulocytes (with tiredness). Another prominent finding was that fat mass explained part of the association between inflammation and altered appetite. Although this has been observed elsewhere, the role of obesity in this link represents a fascinating aspect which remains to be clarified.
What are the possible near-term applications of these findings in clinical practice?
Although further investigations are warranted to disentangle the complex relationship between inflammation and neurovegetative depressive symptoms, our findings may have two potential translational implications in the long-term.
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For eating behavior, they suggest that low-grade (subclinical) inflammation may be a target for the specific treatment of eating disorders (ED). We do not neglect the preponderant role of the psychological component in ED, but increasing evidence suggests that these disorders result from alterations of different domains. Indeed, altered inflammatory cytokine levels have been observed both in anorexia and in bulimia nervosa, which were restored to normal values after renutrition periods. Moreover, strong metabolic correlates have been reported for the genetic underpinnings of anorexia nervosa.
Regarding the tiredness/low energy symptom, our observations are in line with the view that low-grade inflammation may lead to chronic fatigue and may be important in the search for effective treatments for this syndrome, whose biological bases are still poorly understood.
Are you conducting or planning any other research on this topic?
We are now trying to identify the direction of effect of changes in appetite associated with low-grade inflammation, since this was not specified in the scale that we used for assessing depressive symptoms. Similarly, it would be interesting to dissect the role of fat mass and obesity in this relationship, which is largely unclear. Moreover, we are disentangling the nature of the relationship between depressive symptoms and inflammation and their combined effect on the incident risk of major clinical events like hospitalizations and mortality.
Is there anything else pertaining to your research and findings that you would like to add?
Our research is continuously in progress and will likely allow us to get interesting insights into the long hypothesized relationship between depression and inflammation, which remains largely unexplored. We just started to analyze the psychometric scales assessed in our Moli-sani study, which represents a real gold mine from this point of view. So please do expect new interesting findings in the field in the years to come. Stay tuned!
Reference
Alessandro Gialluisi, MSc, PhD, is a postdoctoral researcher at the Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy, where he has researched the molecular and genetic epidemiology of neurodegenerative and psychiatric disorders. He is also a resident in medical statistics and biometry at the Sapienza University of Rome, where he is working on the development and analysis of estimators of biological age based on machine learning algorithms applied to biomedical data. At the Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany, he researched the genetic and neurobiological bases of reading and language abilities.