Lifespan trajectory of affect in Cornelia de Lange syndrome: towards a neurobiological hypothesis

Abstract

Background Depressive symptomology and low affect are comparatively common in individuals with genetic disorders such as Cornelia de Lange syndrome. However, lifespan trajectories and associated person characteristics have not been examined. In this study, the trajectories for affect and associated behavioural characteristics were investigated in individuals with Cornelia de Lange syndrome with individuals with fragile X syndrome (FXS) comparable for chronological age and total number of behavioural indicators of ASD included for the purpose of contrast. Methods A 7-year longitudinal study of affect (mood, interest and pleasure) was conducted in individuals with CdLS ( n = 44) and FXS ( n = 95). The trajectories of low affect were explored, as well as associations between Time 1 behavioural characteristics and affect at Time 1 and Time 3 (7 years later). Results The CdLS group were lower in mood than the FXS group overall ( p < .001). Interest and pleasure scores showed a significant decline over the lifespan for individuals with CdLS ( p < .001) but not the FXS group. Lower level of ability at Time 1 was associated with lower mood at Time 1 and Time 3 in the FXS group only. Higher levels of ASD symptomology at Time 1 were associated with low mood and interest and pleasure in both syndrome groups at Time 1 and Time 3. Greater insistence on sameness at Time 1 was associated with lower mood at Time 1 in the FXS group and lower interest and pleasure at Time 1 and Time 3 in the CdLS group. Conclusions Low affect in specific genetic syndromes may be associated with differing lifespan trajectories and behavioural profiles. Specifically, individuals with CdLS appear at risk for experiencing declines in levels of interest and pleasure whereas individuals with FXS show no significant change in the level of affect with age.

The behavioural phenotype of SATB2-associated syndrome: a within-group and cross-syndrome analysis

“…It is reassuring to note that no negative associations between mood or interest and pleasure subscale scores and chronological age were found, given that decline in levels of affect with age have been reported in other genetic syndrome groups [ 63 , 64 ]. There are several challenges when exploring the mental health profiles of individuals with intellectual disability and autism, particularly the appropriateness of clinical measures and diagnostic criteria when individuals do not communicate using spoken language [ 65 ].…”

Heterogeneity of Autism Characteristics in Genetic Syndromes: Key Considerations for Assessment and Support

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“…Age-related differences are also evident, with repetitive behaviours and social withdrawal becoming more prominent among older individuals and increasing over time [ 23 , 40 ]. Notably, several studies have also associated older age with more frequent self-injury and compulsive behaviour, and lower levels of interest and pleasure in CdLS, indicating that additional challenges are coinciding with age-related changes in autism characteristics in this group [ 51 – 53 ]. The significance of age-related changes experienced by people with CdLS highlights the need to provide additional and/or bespoke support, particularly during the transition to adulthood which is a critical period of change.…”

The developmental trajectories of the behavioral phenotype and neuropsychiatric functioning in Cornelia de Lange and Rubinstein Taybi syndromes: A longitudinal study

“…CdLS patients are likely to show increased severity in social impairments over time, especially social anxiety, social withdrawal, low mood, interest and pleasure, insistence on sameness, challenging behaviors, sleep disorders, and more severe autism spectrum disorder (ASD) symptomatology from 15 years old onward, but receptive language skills improve and adaptive behaviors experience broad stability reaching a plateau phase in adolescence and early adulthood (Ajmone et al, 2021 ; Basile et al, 2007 ; Cochran et al, 2019 ; Giani et al, 2021 ; Grados et al, 2017 ; Moss et al, 2017 ; Nelson et al, 2017 ; Srivastava et al, 2014 ). In addition, Groves et al ( 2019 ) found that individuals with CdLS appear at risk for experiencing lower mood related to a decrease of interest and pleasure compared to Fragile X syndrome over the lifespan.…”