Osteoarthritis and Depression Comorbidity and Intervention
Abstract
Background: Osteoarthritis (OA), the most common form of arthritis, is a leading cause of debilitating pain and disability, affecting > 32 million in the U.S. alone. The prevalence and incidence of OA have been continuously increasing due to increases in lifespan and obesity. The number of OA patients is expected to rise to over 78 million in the U.S. by 2040. In particular, OA has been a substantial burden among Veterans of the U.S. Armed Forces due to the high physical demands of their daily routines. More recently, serious concerns have been raised regarding OA-related chronic comorbid health conditions. For example, individuals with OA have a 2.5-times greater risk of having three or more other chronic diseases. Compared to civilians, Veterans are far more vulnerable to a chronic comorbid health condition – more than a third of veterans suffer from at least two such chronic diseases (e.g., OA and depression). In particular, OA patients show a higher prevalence of the devastating symptoms of depression and anxiety than those without OA. Worse, the synergistic adverse effects of OA and depression have been recognized when they have comorbid conditions. The close relationship between arthritis and mental health is now well recognized. Veterans are disproportionately affected by chronic pain and depression compared to civilians. The data shows: (i) that the rates of depression and anxiety can be 2-10 times higher in arthritic patients than rates in the population without OA; (ii) that anxiety and depression can significantly lower the pain threshold; and (iii) chronic pain aggravates anxiety and depression in a vicious circle. Furthermore, arthritis patients with depression tend to have more serious functional limitations. Such a vicious circle of pain, poor health, and negative mood can significantly change the course and management of the disease. Rationale: Probiotics are mixtures of live bacteria and yeasts that are supposed to improve health by establishing healthy gut microflora, and prebiotics stimulate growth of beneficial bacteria. We identified the best combination of a single strain of probiotic (Lactobacillus acidophilus, LA) and prebiotic oligofructose (FOS), referred to as LA-synbiotic, for the treatment of OA and associated depression. We will evaluate LA-synbiotic as a safe and ideal OA disease-modifying drug in our preclinical animals of knee OA pain that has comorbid depression. Hypothesis: In recent years, vascular endothelial growth factor (VEGF) has emerged as a primary subject of psychiatric research, with an emphasis on its potential role in depressive disorder and stress-related diseases. The circulating serum level of VEGF is identified as a major critical depression disorder determinant, and peripheral VEGF levels are associated with antidepressant response results in clinical studies. The action of VEGF is through activation of VEGFR1 and VEGFR2. We hypothesize that (i) OA and depression comorbidity will drastically magnify joint pain sensation, accelerate OA pathology, and worsen depression via the activation of Flt1 and Flk1 signaling pathways and (ii) the combination of LA with FOS (referred to as LA-synbiotic) will synergize its beneficial effects on joint pain and depressive disorder, establishing a co-treatment strategy. (iii) We also hypothesize that LA-synbiotic-mediated disease-modifying effects on OA and depression occur by altering the VEGF signaling pathways via the production of anti-inflammatory bacterial metabolites, SCFAs that modulate peripheral sensory neuronal plasticity and neuroinflammation. Aim 1: To evaluate a pre-/probiotic combination, LA-synbiotic, for therapeutic efficacy in chronic comorbid disease, OA, and depressive disorder using a knee OA + depression animal model that aggravates OA joint pain. We will evaluate the ability of the LA-synbiotic to reduce aggravated OA pain and depression using our preclinical animal model that mimics human cases (OA joint pa
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210882
Entities
People
- Hee-jeong Im Sampen
Organizations
- United States Army
- University of Illinois at Chicago