RA genetic risk linked to IQ, hyperactivity during childhood
medwireNews: Genetic liability for rheumatoid arthritis (RA) is associated with lower IQ and symptoms of hyperactivity and inattention during childhood and adolescence, supporting a link between genetic risk for the condition and neural phenotypes, UK researchers report.
Hannah Jones (University of Bristol) and colleagues say their findings indicate “that cognitive impairment in RA is not simply secondary to disease-related processes or treatment effects.”
They add: “These results may suggest that genetic susceptibility for RA might affect psychological well-being in early life and reinforce the emerging link between mental health and the immune system.”
The researchers generated polygenic risk scores (PRSs) for 7977 children and adolescents (48.7% female) from the Avon Longitudinal Study of Parents and Children and investigated whether they were associated with cognitive and psychiatric phenotypes.
At age 8 years, when cognitive testing was performed, increased RA PRS was significantly associated with decreased total IQ, performance IQ, and verbal IQ, as measured by the Wechsler Intelligence Scale for Children, with the strongest association seen for verbal IQ.
Jones and team say that this result “is notable because studies in patient groups have shown that verbal function is one of the most robustly affected areas of cognition in RA.”
It suggests “that some of this vulnerability may be mediated through the effects of genetic risk for RA on cognitive function and may not solely be caused by disease-related effects or medication,” they write in JAMA Network Open.
The investigators also found that a higher RA PRS was associated with an increased likelihood for hyperactivity and inattention, assessed using the Strengths and Difficulties Questionnaire, between 4 and 13 years of age, with the strongest association recorded at age 13 years. At this age, each standard deviation increase in PRS was associated with a significant 25% increase in the likelihood for hyperactive and inattentive symptoms.
By contrast, there was no significant association between the RA PRS and other measures of cognition and psychopathology, including working memory, verbal learning, processing speed, problem solving, anxiety, depression, negative symptoms, and psychotic experiences, or markers of inflammation.
To test the selectivity of their results, the researchers looked for similar associations between the cognitive and psychiatric outcomes and PRSs for inflammatory bowel disease and multiple sclerosis but did not find any indicating “a specific effect of pathways associated with genetic risk for RA on the CNS [central nervous system].”
Jones and co-authors conclude that although “RA is currently conceptualized as a multisystem connective tissue disorder,” their findings “suggest that CNS impacts should also be considered a core and primary component of RA, especially in the domain of cognition.”
“Furthermore, they support the view that clinically it is important to assess and monitor cognitive impairment in patients with RA, especially as cognitive factors can affect activities of daily living and individuals’ overall level of functioning.”
They add: “Further studies of the role of immune pathways in regulating cognitive function may also lead to the development of new therapeutic approaches for cognitive impairments in RA and, more broadly, for areas such as [attention-deficit hyperactivity disorder].”
By Laura Cowen
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