Assessment of Pro-Inflammatory Biomarkers and Psychological Profiling of Treatment-Resistant Depression Ref.No.SSTCRC2599
1. Objectives
-to determine the level of pro inflammatory biomarkers (hs-CRP, interleukin 6), vitamins (such as of D, B12, & folic acid), blood parameters, thyroid function, and metabolites among three cohorts of individuals with TRD, without TRD, and healthy participants.
-to establish the psychological profile of individuals with TRD, without TRD, and healthy participants including childhood trauma, social hurt, social exclusion, life style, events, stress, and socio-economic class.
-to explore the relationship of psychological attributes with biological factors between the three cohorts.
-to assess the mediational role of pro inflammatory biomarkers between psychological attributes and duration of TRD after controlling other biological factors.
2. Similar studies
Inflammation-induced studies have provided sufficient empirical evidence for the association of systemic chronic inflammation with mood disorders and other psychiatric disorders (see for instance, Colasanto, Madigan, & Korczak, 2020; Eisenberger & Moieni, 2020; Strawbridge et al., 2018). Chronic inflammation, in contrast to acute inflammation, is the dysregulated and long term immunological reaction of the body. Though inflammation is a natural healing process of immunity to recover from injury or pathogenic invasion, in chronic inflammation, the body continues to produce ‘pro-inflammatory cytokines’ and when continues to be unresolved causes neuroinflammation and a sequelae of self-destructive mechanism in the body (Sun et al., 2022). Several studies have reported that pro-inflammatory cytokines especially Interleukin-6 (IL-6), which triggers the production of C-Reactive Protein (CRP, measured through hs-CRP) mainly in the liver, are together implicated in sabotaging the effects of anti-depressants in individuals with major depression disorders (Raison et al., 2013) and in predicting Treatment Resistant Depression (TRD; Liu et al., 2021).
3. Research Progress
-Development and Validation of Scale to measure Treatment Resistant Depression (TRD) is under way.
-Data regarding antidepressants commonly prescribed has been accumulated.
4. Cooperation Required
-Research experts belonging to different countries of Asia.
-Funds for conducting the study.
5. Benefits
1. Culture Fare Measurement of TRD: One of the critical issue related to investigation of treatment non-responsive psychiatric illnesses is the standardized operationalization and measurement of the construct. Though ‘depression’ is considered a universal mental health problem, its features have shown cultural and ethnic diversity in manifestation. For instance, it has been observed that in South Asian countries including Pakistan, ‘sleep problems’ are the most frequently reported diagnostic symptoms of depression while ‘headaches & issues with heart’ have been observed as most frequent non-diagnostic features (in accordance to DSM V; Haroz et al., 2017). Therefore, the present study is expected to produce an assessment protocol to objectively measure major depression and TRD accounting for cultural and ethnic variations in Pakistan.
2.Efficient Assessment Procedure: Among the prime objectives of the project is to establish hs-CRP and interleukin-6 as the inflammatory biomarkers and predictors of the TRD. In a study conducted in China, hs-CRP indices of 10.5 mg/L (100 nmol/L) or above is considered as a cut off for the diagnosis of TRD (Qiao et al. 2019). Qiao et al. also found that among different diagnosable clinical features of TRD, anxiety/somatization strongly and significantly related with hs-CRP followed by sleep disorders, while cognitive disorders, retardation, and weight were found to be non-significantly related with hs-CRP among individuals with TRD. In one of the previous studies, Miller et al. (2017) found that CRP level with < 3 mg/L is associated with TRD. Similarly, one of the most recent study conducted in Kingdom of Saudi Arabia found high levels of hs-CRP in individuals with TRD as compared to individuals with non-TRD (Almutabagani et al., 2023).
3.Psychological and Biological Characteristics of TRD: The studies on TRD (see, for example, Miller et al, 2017; Qiao et al, 2019) have attempted to formulate a distinctive clinical and biological profile of TRD in comparison to non-TRD. Research indicates that both groups may also be differentiated on the basis of personal life experiences, life style, health-related behaviors, and stress-response (Buoli et al., 2022). The present project is expected to provide a distinctive psychological profile of TRD, which will help in addressing the specific psychological correlates and planning preventive measures. In similar vein, the study will also provide insight into the potent biological correlates (Halaris et al., 2021) such as vitamins and cholesterol, which will also guide primary health and preventive protocols.
4.Reduction in Socioeconomic Burden and SDG 3: One of the overarching outcome expected with the present project is to reduce the socioeconomic burden related with TRD. According to an estimate conducting in 2004 (when 1 US $ was equivalent to 58 PKR), the direct health care cost of depression amounted to 10.58 billion $US in Pakistan (Gadit, 2004). With the development of cost effective and less time consuming diagnostic techniques, it is expected that the present project will contribute in reducing socioeconomic burden for TRD disease in Asian countries. In addition, this study is expected to provide emotional and social relief to the individuals suffering from non-treatable depression and their caregivers by providing an empirically validated treatment.
5.Business Potential of the Study: If established that chronic inflammation is linked with TRD, pharmaceutical companies can design low cost and efficient biomarkers for the diagnosis of TRD. Moreover, the possibility of correlating biological factors such as vitamins and cholesterol will also guide the pharmaceutical companies to produce precision medicines for the treatment of TRD. On the other hand, psychiatrists and medical practitioners will also be able to provide effective treatment plans to their patients.