The association between inflammatory markers and psychological disorders in veterans and military personnel: a systematic review protocol

Field: Medicine (Health Sciences)

Review questions(s)/objective(s) The objective of this systematic literature review is to identify whether there is an association between inflammatory markers and psychological disorders in veterans and military personnel. The primary question to be examined is: Is there an association between increased inflammatory markers and psychological disorders in military personnel or veterans? Background Although much has been done to better understand the trajectory of psychological conditions, particularly in relation to early intervention and treatment outcomes, the specific risk factors that contribute to the development of some psychological disorders are not always clear. Emerging literature, however, suggests biomarkers and inflammatory markers, such as cytokines, may provide a promising method to identify risk for developing certain health conditions, such as cardiovascular disease,1,2 bipolar disorder3 and metabolic conditions.4,5 They have also been linked to disorders of the central nervous system and damage to neurological tissue contributing to diseases such as Alzheimer's and Parkinson's.6 The association between immune and inflammatory responses on mental health and psychological disorders are still relatively unknown however, there is some suggestion that high levels of inflammation measured by Interleukins (IL) and C-Reactive Protein (CRP) may be associated with symptoms of Post-Traumatic Stress Disorder (PTSD)6,7 and depressive conditions.3,8 For example, Eraly4 investigated whether inflammatory markers could be used to predict PTSD in a sample of approximately 2600 military personnel. The results indicated that CRP was a significant overall predictor of likelihood to develop PTSD symptoms in personnel who had deployed. These findings are supported by Gill et al.,9 who examined the quality of life and psychological outcomes in military personnel and identified that individuals with PTSD and depression not only had substantial risks of lower quality of life but also displayed an increase in inflammation as measured by IL. The production of cytokines, a further indicator of inflammation, was also shown to increase in military personnel who have deployed and demonstrated the potential to remain in an elevated state for an extended period of time10 Whilst inflammatory markers cannot be used to definitively diagnose a psychological condition, it is possible they could depict the presence or absence of symptoms, which in turn could assist health professionals in a different diagnosis or case formulation process.4 For currently serving military personnel and veterans, it is generally accepted that combat exposure is likely to create a high level of physical and psychological stress, which will in turn activate inflammatory responses. The use of inflammatory markers may provide an objective measure that can assist in identifying individuals who are more likely to experience changes at a later stage. In a military context, this could enable personnel who are perceived to be at high risk of developing conditions, due to the requirements of their employment (e.g. exposure to combat or other traumatic events), to access resources or support that could be preventative and allow for early intervention or treatment before symptoms manifest or become problematic. Research into the effects of systemic inflammation on disease and health issues is developing. It is worthwhile considering how inflammation contributes to psychological development or changes, particularly as psychological stress has been known to place excessive demands on the physiological system.9,11,12 Individual differences, such as personality traits or coping styles, may also determine whether some individuals are more likely to develop inflammatory responses, which could make them vulnerable to psychological and other health related conditions. While there is some primary research on health outcomes, such as psychological disorders in military populations, there is currently no systematic literature review addressing the question of whether inflammation is associated with changes in mental health. This systematic review will explore existing evidence in order to understand whether there is an association between increased inflammatory markers and psychological disorders. Gaps in the current evidence base may be identified and this review may offer directions for future primary research. Inclusion criteria Types of participants This review will consider studies that include currently serving military personnel, as well as individuals who have already left the military (veterans). Military populations of all countries and all ethnicities will be considered. Both females and males will be considered. No age restrictions will be applied. This review will exclude studies that involve participants undergoing basic recruit or military training as this population is not considered to have met the definition of being a currently serving military member, or a military veteran in the sense of having had a period of service, or been deployed and involved in a period of active duty. Phenomena of interest The phenomena of interest in this review are inflammatory markers and psychological disorders. Studies that seek to identify changes in inflammatory markers and the presence or absence of psychological disorders will be considered. Specific inflammatory markers are likely to include C-Reactive Protein, Interleukin-6, and Tumour Necrosis Factors. Psychological disorders of interest will include posttraumatic stress disorder, depression and anxiety related conditions, adjustment disorder as well as somatic complaints; however, studies which have sought to identify other psychological disorders will also be considered. Types of outcomes The outcome of interest will include an association between inflammatory markers and the symptoms associated with psychological disorders. Inflammatory markers are detected through physical testing, such as blood samples or saliva. The presence of a psychological disorder can be determined by the use of a range of techniques, including questionnaires and interviews that allow symptoms to be classified according to the Diagnostic and Statistical Manual of Mental Disorders (DSM). The DSM has been developed by the American Psychiatric Association and is a widely used clinical and research tool that provides a standardized system of classifying psychological or mental health conditions and collating public health statistics. For the purpose of this review, symptoms of psychological disorders that are considered, such as PTSD or depression, will be in accordance with the DSM criteria. Types of studies The review will consider all associations and correlational studies including: randomized controlled trials, cohort or case controlled prospective or retrospective studies, cross sectional samples, longitudinal or before and after studies. Search strategy The search strategy aims to find published studies. A three-phase process will be implemented in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by an analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Only studies published in English will be considered for inclusion. To avoid excluding potentially relevant material, dates of published material will not be confined to a specific period. Grey literature will not be included in this systematic literature review as it is important to consider the quality and rigour of the evidence. The databases to be searched include: EBSCO CINAHL Embase OVID Medline PsycINFO Web of science Initial keywords to be used will be: Military, Veterans, Military Personnel, Military, Army, Defence, Marines, Soldiers, Sailors, Air force, Navy, Rangers, Paratroopers, Commando, Special Forces, Infantry Psychological Disorder, Mental Health, Post-Traumatic Stress, Depression, Anxiety, Combat Disorder, Mental Disorder Inflammatory markers, Inflammation, Interleukin (IL), Cytokines, CRP, TNF Assessment of methodological quality Quantitative papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using the appropriate standardized critical appraisal instrument from the Joanna Briggs Institute suite of instruments for appraising quantitative studies (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion and, if necessary, with a third reviewer. Data collection Quantitative data will be extracted from papers included in the review using the standardized extraction tool from JBI-MAStARI (Appendix II). This will minimize the risk of error and ensure the same data is recorded for each study included in the review. To assist with reliable data entry, reviewers will be required to practise using the tool and apply it consistently prior to studies being examined. Details regarding the population of interest, methods, outcome measures and results will be extracted from studies included in this review that relate to the specific question and objective. If required, authors of primary studies may be contacted to obtain missing information or clarify referenced data. Data synthesis Quantitative data will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as risk or odds ratios, correlation coefficients or mean differences, along with 95% confidence intervals, will be calculated for analysis. A random effects model and heterogeneity will be assessed statistically using the standard Chi-square. Where statistical pooling or meta-analysis is not possible, narrative and tables will be used to synthesize the data. Conflicts of interest None to declare. Acknowledgements This systematic literature review is being undertaken as part of the requirements for a PhD.