Systemic inflammation linked to symptom-specific depression effects

Systemic inflammation appeared to have symptom-specific rather than generalized effects on depression, according to results of a random-effects pooled analysis published in American Journal of Psychiatry.

“Previous evidence on the role of inflammation in depression etiology has largely ignored the possibility of inflammation being related to a specific symptom profile of depression rather than depression more generally,” Philipp Frank, MSc, of the research department of epidemiology and public health at University College London, told Healio Psychiatry. “Moreover, most studies had small sample sizes and did not take into account the potential influence of confounding factors (eg, chronic illnesses).

“Our study, the largest study to date on this subject, brought together raw data from 15 population-based cohorts comprising over 55,000 individuals [aged 18 years or older] and examined the association between two inflammatory markers and an array of depression-related symptoms, considering the potential influence of socio-demographic, lifestyle and illness related factors.”

Frank and colleagues analyzed data on participants’ serum or plasma concentrations of C-reactive protein measured at baseline. Across 15 cross-sectional studies, researchers used validated self-report measures to ascertain 24 depressive symptoms. Further, they assessed these symptoms at follow-up (mean follow-up period, 3.2 years) among seven cohorts.

Results showed depressive symptom prevalence ranged between 1.1% for suicidal ideation to 21.5% for sleep problems. Cross-sectional analyses showed a robust association between higher concentrations of C-reactive protein and increased risk for experiencing physical symptoms, including changes in appetite, feeling everything was an effort, loss of energy and sleep problems, as well as one cognitive symptom, which was little interest in doing things. After the researchers adjusted for sociodemographic variables, behavioral factors and chronic conditions, these associations remained. They also remained in sex- and age-stratified analyses, longitudinal analyses, upon using interleukin-6 as the inflammatory marker of interest, among individuals with depression and after exclusion of individuals with a chronic illness.

The overall evidence strongly countered the association with inflammation for four exclusively emotional symptoms, which were being bothered by things, hopelessness about the future, feeling fearful and feeling life had been a failure.

“Ascertaining robust symptom-specific associations may inform future research, particularly clinical trials that aim to examine the potential anti-depressant effects of anti -inflammatory therapies,” Frank said. “Our results indicate that inflammation is primarily associated with physical (eg, changes in appetite, sleep problems, lower energy levels) but not emotional (eg, fearfulness) symptoms.

“Anti-inflammatory therapies may therefore be most beneficial for people who experience symptoms identified in this study,” Frank added. “This may ultimately help the design of more targeted treatment regimens for people with an inflammation-related subtype of depression.”