The role of genes, intelligence, personality, and social engagement in cognitive performance in Klinefelter syndrome

Abstract

IntroductionThe determinants of cognitive deficits among individuals with Klinefelter syndrome (KS) are not well understood. This study was conducted to assess the impact of general intelligence, personality, and social engagement on cognitive performance among patients with KS and a group of controls matched for age and years of education.MethodsSixty‐nine patients with KS and 69 controls were assessed in terms of IQ, NEO personality inventory, the Autism Spectrum Quotient (AQ) scale, and measures of cognitive performance reflecting working memory and executive function.ResultsPatients with KS performed more poorly on memory and executive‐function tasks. Patients with KS also exhibited greater neuroticism and less extraversion, openness, and conscientiousness than controls. Memory deficits among patients with KS were associated with lower intelligence, while diminished executive functioning was mediated by both lower intelligence and less social engagement.ConclusionOur results suggest that among patients with KS, memory deficits are principally a function of lower general intelligence, while executive‐function deficits are associated with both lower intelligence and poorer social skills. This suggests a potential influence of social engagement on executive cognitive functioning (and/or vice‐versa) among individuals with KS, and perhaps those with other genetic disorders. Future longitudinal research would be important to further clarify this and other issues discussed in this research.

Reversal learning performance in the XY* mouse model of Klinefelter and Turner Syndromes

“…These results indicate that gonadal function moderates the impact of X-dose on impulsivity and learning, respectively, in the XY* model of KS. Nevertheless, in KS men, androgen therapy in adulthood does not appear to affect these aspects of learning and cognition (Fales et al, 2003; Kompus et al, 2011; Liberato et al, 2017; Skakkebæk et al, 2017).…”

“…These results may have implications for the use of androgens to remedy the cognitive deficits observed in KS men. Although androgen therapy does not appear to improve cognition in either KS adults (Skakkebæk et al, 2017) or children (Ross et al, 2017), little is known about the consequence of either an increased severity of hypogonadism and/or the lack of standard androgen replacement therapy on cognitive function. Our results indicate that in XXY mice, even small changes in circulating androgens can significantly change cognitive processes and learning.…”

“…We expected that if genotypes differed on behavioral measures, that some of the differences might disappear if they depended on group differences in levels of gonadal hormones in any life stage. However, sex- hormone replacement therapies in adulthood do not appear to remediate the cognitive deficits observed in people with KS (Fales et al, 2003; Kompus et al, 2011; Liberato et al, 2017; Skakkebæk et al, 2017) or TS (Klein et al, 2018; Ross et al, 2002, 2004), and the cognitive consequences of reducing/blocking sex hormones in people with either KS or TS, or in this animal model, are unknown.…”

“…Although the data are limited, mouse models of KS do appear to have some face validity in terms of learning impairments (Ross et al, 2008; Rovet et al, 1996; Skakkebæk et al, 2017). For example, in a novel-object recognition test, XXY mice from the XY* model failed to show the typical pattern of more exploration of the novel object relative to the more familiar object, but control XY mice did (Lewejohann et al, 2009).…”

Anxiety and depression in Klinefelter syndrome: The impact of personality and social engagement

“…The study was approved by The Danish Data Protection Agency and local ethics committee (Region Midtjylland, Denmark number M-20080238) and registered at ClinicalTrials.gov (Clinical trial NCT00999310). Certain neuropsychological data from this research has been presented previously to address separate research questions [ 20 ; 32 ; 33 ].…”