Why Are Some People with Lower Urinary Tract Symptoms (LUTS) Depressed? New Evidence That Peripheral Inflammation in the Bladder Causes Central Inflammation and Mood Disorders

Abstract

Anecdotal evidence has long suggested that patients with lower urinary tract symptoms (LUTS) develop mood disorders, such as depression and anxiety, at a higher rate than the general population and recent prospective studies have confirmed this link. Breakthroughs in our understanding of the diseases underlying LUTS have shown that many have a substantial inflammatory component and great strides have been made recently in our understanding of how this inflammation is triggered. Meanwhile, studies on mood disorders have found that many are associated with central neuroinflammation, most notably in the hippocampus. Excitingly, work on other diseases characterized by peripheral inflammation has shown that they can trigger central neuroinflammation and mood disorders. In this review, we discuss the current evidence tying LUTS to mood disorders, its possible bidirectionally, and inflammation as a common mechanism. We also review modern theories of inflammation and depression. Finally, we discuss exciting new animal studies that directly tie two bladder conditions characterized by extensive bladder inflammation (cyclophosphamide-induced hemorrhagic cystitis and bladder outlet obstruction) to neuroinflammation and depression. We conclude with a discussion of possible mechanisms by which peripheral inflammation is translated into central neuroinflammation with the resulting psychiatric concerns.

Mitigating Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: Ameliorating Sexual Function and Psychological Well-Being in Older Men

“…LUTS secondary to BPH can negatively affect mental health by causing anxiety, depression, and social isolation. The frustration and embarrassment associated with LUTS can lead to anxiety and depression, further exacerbating sexual dysfunction (Hughes et al, 2023; Martin et al, 2022). Men with BPH-related LUTS often report feelings of embarrassment and frustration, which can lead to social isolation and reduced participation in social activities.…”

Adverse childhood experiences and lower urinary tract symptoms in adolescence: the mediating effect of inflammation

“…The physiological changes include an increased risk of systemic inflammation, 24 which in turn, has been implicated as a risk factor for LUTS. 13 There is evidence from animal models that exposure to chronic psychological stress and early life adversity can impact on lower urinary tract function due to functional and structural changes in the bladder, especially in the detrusor muscle and urothelium, and can lead to hypersensitivity of the afferent nerves in the bladder. 25 We cannot rule out reverse causality as a possible explanation for the relationship between ACEs and LUTS.…”

“…One plausible biological mechanism is through ACEs leading to increased inflammation. 12 Inflammation has also been implicated as a contributing factor for LUTS, 13 but no cohort studies have examined this in paediatric samples.…”

Emerging role of the host microbiome in neuropsychiatric disorders: overview and future directions

“…Notably, there is evidence suggesting a link between overactive bladder and psychiatric disorders such as depression and anxiety [ 170 , 171 ]. A national cohort study conducted in Taiwan demonstrated significantly higher risk of depression and anxiety in patients with overactive bladder compared to those without overactive bladder [ 172 ].…”