Early-life gastrointestinal inflammation and the developing brain: Unravelling the pathways to long-term cognitive dysfunction

Table 6 Summary of studies: Pediatric inflammatory bowel disease and neurocognitive outcomes

Ref.	Population/condition	Key cognitive/functional findings	Key mechanistic/psychosocial findings	Implication/conclusion
Tadin Hadjina et al[157], 2019	Adult IBD patients (n = 60) vs controls	Impaired neurocognitive and psychomotor function: Significantly longer total test-solving time in tests for convergent thinking, perceptive abilities, and complex operative thinking	Deficits in mental processing speed and mental endurance	IBD patients show objective impairment in cognitive and psychomotor speed, even in adulthood
Clarke et al[159], 2020	Adult Crohn’s disease and UC patients in clinical remission (prospective)	Impaired attentional performance was a stable feature of Crohn’s disease patients over a 6-month period (UC patients were unaffected)	Consistently elevated plasma IL-6 and kynurenine-to-tryptophan ratio; blunted cortisol awakening response. No correlation between biochemical markers and cognitive impairment was found, but the markers indicated ongoing, subclinical inflammation	Impaired cognitive function is a stable feature of Crohn’s disease, likely driven by persistent inflammatory/metabolic changes
Castaneda et al[158], 2013	Adolescents with IBD (n = 34) vs peers with JIA	IBD group, especially those in the acute phase, made more perseverative errors in the California Verbal Learning Test (verbal memory), suggesting executive function deficits	IBD group had more depressive symptoms than JIA group (especially with acute illness). Depressive symptoms were not related to the cognitive difference	Acute IBD may cause mild verbal memory/executive function problems; psychosocial burden (depression) is significant
Herzer et al[160], 2011	Adolescents with IBD (n = 62) and their caregivers	Poorer HRQOL across multiple dimensions (emotional, social, total HRQOL)	Adolescent depressive symptoms fully mediated the relation between parent distress (illness-related stress) and the youth’s poorer HRQOL	Psychosocial factors (parental distress-adolescent depression) are crucial targets for intervention to improve HRQOL
Friedman et al[161], 2020	Children exposed to maternal IBD in utero (followed to 7 years)	Children exposed to IBD in utero scored similarly to unexposed children on survey-based tools assessing motor and cognitive development	No obvious differences in language, motor, or cognitive/behavioral scores at 7 years	Reassuring data suggesting that maternal IBD exposure alone does not increase the risk of long-term neurodevelopmental delay

It summarizes human-based findings concerning the cognitive, functional, and psychosocial impacts of inflammatory bowel disease on children and adolescents. Studies demonstrate that inflammatory bowel disease, particularly Crohn’s disease, is associated with persistent deficits in executive functions and mental processing speed, often linked to systemic inflammation (interleukin-6, kynurenine-to-tryptophan ratio). Critically, the psychosocial burden is high, with adolescent depressive symptoms serving as a key mediator between parental distress and poor health-related quality of life. IBD: Inflammatory bowel disease; HRQOL: Health-related quality of life; JIA: Juvenile idiopathic arthritis; UC: Ulcerative colitis.