Associations between Inflammation and Mental Health Challenges In Adults with Down Syndrome

Background and Purpose: Currently 1 in 640 live births in the United States involves Down syndrome, a developmental disability caused by having three copies of chromosome 21. Individuals with Down syndrome are at high-risk for co-occurring mental health challenges. Yet, this community faces a health disparity in that they have been historically excluded from research and intervention trials; thus, relatively little is known about biological correlates of these challenges. Outside of Down syndrome, there is robust evidence that mental health challenges are related to elevated systemic inflammation, including high levels of interleukins (IL), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP); these may contribute to neuroinflammation in aging, including elevated neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). The current study fills a gap in knowledge by examining the association between the mental health challenges of adults with Down syndrome and blood biomarkers of systemic and neuroinflammation. This information is critical for informing intervention options and promoting the health of adults with Down syndrome.

Methods: Data came from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS), a multisite study conducted in the U.S., U.K., and Puerto Rico. Sample size ranged from N=151 to N=328 across biomarkers (which were added to the study at different time points). Mental health symptoms were measured using the Reiss Screen for Maladaptive Behavior (RSMB) which assesses (a) aggression, (b) restrictive and repetitive behavior, (c) psychosis, (d) paranoia, (e) depression-behavior, (f) depression-physical, (g) dependent personality, and (h) avoidance. Pearson correlations examined the association between sociodemographic variables (age, sex, and body mass index [BMI]), inflammatory biomarkers, and RSMB scores. Inflammatory biomarkers were winsorized to manage non-normal distributions. Linear regression models were conducted to examine the association between inflammatory biomarkers and Total RSMB score, which was log-transformed due to positive skewness. All analyses were conducted in SPSS v28.

Results: TNF-α (r = .171, p =.028) and GFAP (r = .124, p =.025) were significantly positively correlated with Total RSMB score. TNF-α was significantly correlated with depression-physical (r =.244, p =.002). GFAP was significantly correlated with psychosis (r =.122, p = .027), depression-behavior (r = .125, p =.024), and avoidance (r = .124, p =.025). NfL was significantly correlated with depression-behavior (r = .202, p = .010), dependent personality (r = .194, p = .013), and avoidance (r = .163, p = .038). When controlling for sociodemographic variables in regression models, GFAP (β = .190, p =.016) remained significantly positively related to the Total RSMB score. BMI was significant in all regression models (βs = .166-.270, ps <.01).

Conclusions and Implications: In adults with Down syndrome, mental health challenges are associated with elevated neuroinflammation. These results can inform comprehensive approaches to preventing neuroinflammation and mental health challenges, including lifestyle interventions (e.g., physical activity, sleep) and psychosocial interventions for adults with intellectual disability. Findings warrant future explorations of the likely bidirectional ties between neuroinflammation and mental health challenges in adults with Down syndrome and can help guide services and treatment strategies for this underserved population.