The emergence of psychotic experiences in the early adolescence of 22q11.2 Deletion Syndrome

Abstract

Individuals with 22q11.2 Deletion Syndrome (22q11.2DS) are at substantial increased risk of psychosis spectrum outcomes including schizophrenia. We conducted a prospective, longitudinal study of the psychopathological and neurocognitive correlates of early psychotic phenomena in young people with 22q11.2DS (n = 75, mean age time 1 (T1) 9.9 years, time 2 (T2) 12.5 years). We also assessed unaffected control siblings (n = 33, mean age T1 10.6 years, T2 13.4 years). The prevalence of psychotic experiences, defined as subthreshold psychotic phenomena, substantially increased in children with 22q11.2DS from 4% (n = 3) in childhood (T1) to 21% (n = 16) in early adolescence (T2) (p = 0.001), and at T2 prevalence was significantly elevated (p = 0.020) relative to control siblings (3%). The emergence of psychotic experiences was associated with levels of childhood anxiety symptoms at T1 and differential development of the attention-executive domain. IQ ability and IQ change, however, were not associated with the emergence of psychotic experiences, indicating that initial changes in attention-executive functioning may precede the decline in global cognition that has been reported to be associated with later stages of psychosis development. Our study highlights that psychotic phenomena emerge early in 22q11.2DS and we implicate attention-executive functioning and anxiety as key domains associated with the development of these psychotic experiences.

Cognitive deficits in childhood, adolescence and adulthood in 22q11.2 deletion syndrome and association with psychopathology

“…Furthermore, although there were significantly more females in adult individuals with 22q11.2DS than controls running all analyses with gender as a covariate did not change results. As some participants were unable to complete the assessments, it's possible that our findings may not represent those individuals with the greatest cognitive deficits 8 .…”

“…Several studies have established a high prevalence of childhood psychopathology manifesting as attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and anxiety disorders 2,3 . Prevalence of psychiatric disorders appears to follow different trajectories over the lifespan, such as the rate of anxiety disorders remaining relatively stable across developmental stages 6 , whereas the rate of ADHD diagnosis declines, with 33-43% individuals no longer reaching diagnostic criteria at follow-up in adolescence 7,8 . Therefore, it is important to take a developmental perspective when considering psychiatric disorders in 22q11.2DS, which reflects the dynamic development of the brain.…”

Atypical response inhibition and error processing in 22q11.2 Deletion Syndrome and schizophrenia: Towards neuromarkers of disease progression and risk

“…Importantly, neither the clinical presentation, nor the clinical path leading to psychosis appear to significantly differ between idiopathic and 22q11.2DS-associated schizophrenia ( Hans et al, 2000 , Welham et al, 2009 ). For instance, among other deficits described across perception and cognition, executive function has been implicated as one of the key domains in the development of psychotic experiences in both syndromic ( Chawner et al, 2019 , Maeder et al, 2016 , Tang and Gur, 2017 ) and idiopathic schizophrenia (e.g., ( Niarchou et al, 2015 , Rossi et al, 2016 )).…”

Clinical evaluation of patients with a neuropsychiatric risk copy number variant

“…Also diagnosing psychiatric conditions within the context of multimorbid physical health problems can provide challenges, for instance cleft palate problems can make it difficult to assess the communication domain of autism [ 40 ]. Multi-informant interviews with parent and child are important, particularly for psychotic phenomena when the child may have experiences that the parent is not aware of [ 41 ]. It is important that the mental health needs of the child’s parents are not neglected, as compared to the general UK population parents of CNV carriers have are more likely to experience emotional distress [ 42 • ]; parents of child CNV carriers may need help to access respite care, social support, disability benefits, and counselling.…”