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

ABSTRACT: 22q11.2 Deletion Syndrome (22q11.2DS) is associated with high risk of psychiatric disorders and cognitive impairment. It remains unclear to what extent key cognitive skills are associated with psychopathology, and whether cognition is stable over time in 22q11.2DS. 236 children, adolescents and adults with 22q11.2DS and 106 typically developing controls were recruited from three sites across Europe. Measures of IQ, processing speed, sustained attention, spatial working memory and psychiatric assessments were completed. Cognitive performance in individuals was calculated relative to controls in different age groups (children (6-9 years), adolescents (10-17 years), adults (18+ years)). Individuals with 22q11.2DS exhibited cognitive impairment and higher rates of psychiatric disorders compared to typically developing controls. Presence of Autism Spectrum Disorder symptoms was associated with greater deficits in processing speed, sustained attention and working memory in adolescents but not children. Attention deficit hyperactivity disorder in children and adolescents and psychotic disorder in adulthood was associated with sustained attention impairment. Processing speed and working memory were more impaired in children and adults with 22q11.2DS respectively, whereas the deficit in sustained attention was present from childhood and remained static over developmental stages. Psychopathology was associated with cognitive profile of individuals with 22q11.2DS in an age-specific and domain-specific manner. Furthermore, magnitude of cognitive impairment differed by developmental stage in 22q11.2DS and the pattern differed by domain.

SUBMITTER: Morrison S

PROVIDER: S-EPMC7026075 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Morrison Sinead S Chawner Samuel J R A SJRA van Amelsvoort Therese A M J TAMJ Swillen Ann A Vingerhoets Claudia C Vergaelen Elfi E Linden David E J DEJ Linden Stefanie S Owen Michael J MJ van den Bree Marianne B M MBM

Translational psychiatry 20200203 1

22q11.2 Deletion Syndrome (22q11.2DS) is associated with high risk of psychiatric disorders and cognitive impairment. It remains unclear to what extent key cognitive skills are associated with psychopathology, and whether cognition is stable over time in 22q11.2DS. 236 children, adolescents and adults with 22q11.2DS and 106 typically developing controls were recruited from three sites across Europe. Measures of IQ, processing speed, sustained attention, spatial working memory and psychiatric ass ...[more]

PMID: 32066691

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Project description:Objectives22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion syndrome and has a multisystemic presentation including gastrointestinal features that have not yet been fully described. Our aim was to examine lifetime gastrointestinal problems in a large cohort of patients with 22q11.2DS.MethodsAll patients followed in the 22q and You Center at the Children's Hospital of Philadelphia (n = 1421) were retrospectively screened for: 1) age ≥ 17 years, 2) documented chromosomal microdeletion within the 22q11.2 LCR22A-LCR22D region, and 3) sufficient clinical data to characterize the adult gastrointestinal phenotype. Gastrointestinal problems in childhood, adolescence, and adulthood were summarized. Statistical association testing of symptoms against other patient characteristics was performed.ResultsIncluded patients (n = 206; 46% female; mean age, 27 years; median follow-up, 21 years) had similar clinical characteristics to the overall cohort. Genetic distribution was also similar, with 96% having deletions including the critical LCR22A-LCR22B segment (95% in the overall cohort). Most patients experienced chronic gastrointestinal symptoms in their lifetime (91%), but congenital gastrointestinal malformations (3.5%) and gastrointestinal autoimmune diseases (1.5%) were uncommon. Chronic symptoms without anatomic or pathologic abnormalities represented the vast burden of illness. Chronic symptoms in adulthood are associated with other chronic gastrointestinal symptoms and psychiatric comorbidities ( P < 0.01) but not with deletion size or physiologic comorbidities ( P > 0.05). One exception was increased nausea/vomiting in hypothyroidism ( P = 0.002).ConclusionsFunctional gastrointestinal disorders (FGIDs) are a common cause of ill health in children and adults with 22q11.2DS. Providers should consider screening for the deletion in patients presenting with FGIDs and associated comorbidities such as neuropsychiatric illness, congenital heart disease, and palatal abnormalities.

Project description:ImportanceCognitive deficits are core features of mental disorders and are important in predicting long-term prognosis. However, it is still unknown whether individual patterns of cognitive deficits predate specific mental disorders.ObjectiveTo investigate the specificity of the associations of attention, working memory, and inhibition in childhood with borderline personality disorder (BPD), psychosis, depression, and hypomania in adolescence and young adulthood.Design, setting, and participantsThis cohort study obtained data from the Avon Longitudinal Study of Parents and Children in the United Kingdom. All pregnant women resident in Avon, United Kingdom, with an expected date of delivery from April 1, 1991, and December 31, 1992, were eligible. Data analysis was conducted from April 1 to September 30, 2020. The sample initially comprised 13 988 participants who were alive at 1 year of age. For this study, data were available for 6333 individuals reporting on any psychopathological measure at ages 11 to 12 years, 4903 individuals at ages 17 to 18 years, and 2963 individuals at 22 to 23 years.ExposuresSustained attention, selective attention, and attentional control were assessed with the Test of Everyday Attention for Children at age 8 years, and working memory and inhibition were assessed at age 10 years with the Counting Span Task and the stop-signal paradigm, respectively.Main outcomes and measuresSymptoms of BPD were assessed at ages 11 to 12 years, psychotic experiences and depression were examined at ages 17 to 18 years, and hypomania was examined at ages 22 to 23 years.ResultsAmong 5315 individuals included in the statistical analysis, 2551 (48.0%) were male and 2764 (52.0) were female. Higher sustained attention at 8 years was associated with decreased risk of BPD symptoms at ages 11 to 12 years (adjusted odds ratio [aOR], 0.964; 95% CI, 0.933-0.996; P = .03), better performance on inhibition at age 10 years with decreased risk of psychotic experiences at ages 17 to 18 years (aOR, 0.938; 95% CI, 0.890-0.989; P = .02), higher sustained attention at age 8 years with decreased risk of depressive symptoms at ages 17 to 18 years (aOR, 0.969; 95% CI 0.938-0.9997; P = .048), and better performance in working memory at age 10 years with decreased risk of hypomania symptoms at ages 22 to 23 years (aOR, 0.694; 95% CI, 0.529-0.911; P = .008). After controlling for potential psychopathological overlay, all the associations remained, except for working memory and hypomania. Higher sustained attention at age 8 years was associated with decreased risk of BPD symptoms at ages 11 to 12 years (β = -0.05; P < .001) and of depression at ages 17 to 18 years (β = -0.03; P = .04), and better performance in inhibition at age 10 years was associated with decreased risk of psychotic experiences at ages 17 to 18 years (β = -0.03; P = .04).Conclusions and relevanceThese findings suggest that specific cognitive deficits in childhood are distinctively associated with different psychopathological symptoms in young people. Furthermore, these results suggest the potential of early cognitive interventions in childhood as a way of modifying or attenuating risk for subsequent psychopathological symptoms.

Project description:ImportanceAir pollution exposure damages the brain, but its associations with the development of psychopathology are not fully characterized.ObjectiveTo assess whether air pollution exposure in childhood and adolescence is associated with greater psychopathology at 18 years of age.Design, setting, and participantsThe Environmental-Risk Longitudinal Twin Study is a population-based cohort study of 2232 children born from January 1, 1994, to December 4, 1995, across England and Wales and followed up to 18 years of age. Pollution data generation was completed on April 22, 2020; data were analyzed from April 27 to July 31, 2020.ExposuresHigh-resolution annualized estimates of outdoor nitrogen oxides (NOx) and particulate matter with aerodynamic diameter less than 2.5 μm (PM2.5) linked to home addresses at the ages of 10 and 18 years and then averaged.Main outcomes and measuresMental health disorder symptoms assessed through structured interview at 18 years of age and transformed through confirmatory factor analysis into continuous measures of general psychopathology (primary outcome) and internalizing, externalizing, and thought disorder symptoms (secondary outcomes) standardized to a mean (SD) of 100 (15). Hypotheses were formulated after data collection, and analyses were preregistered.ResultsA total of 2039 participants (1070 [52.5%] female) had full data available. After adjustment for family and individual factors, each interquartile range increment increase in NOx exposure was associated with a 1.40-point increase (95% CI, 0.41-2.38; P = .005) in general psychopathology. There was no association between continuously measured PM2.5 and general psychopathology (b = 0.45; 95% CI, -0.26 to 1.11; P = .22); however, those in the highest quartile of PM2.5 exposure scored 2.04 points higher (95% CI, 0.36-3.72; P = .02) than those in the bottom 3 quartiles. Copollutant models, including both NOx and PM2.5, implicated NOx alone in these significant findings. NOx exposure was associated with all secondary outcomes, although associations were weakest for internalizing (adjusted b = 1.07; 95% CI, 0.10-2.04; P = .03), medium for externalizing (adjusted b = 1.42; 95% CI, 0.53-2.31; P = .002), and strongest for thought disorder symptoms (adjusted b = 1.54; 95% CI, 0.50-2.57; P = .004). Despite NOx concentrations being highest in neighborhoods with worse physical, social, and economic conditions, adjusting estimates for neighborhood characteristics did not change the results.Conclusions and relevanceYouths exposed to higher levels of outdoor NOx experienced greater psychopathology at the transition to adulthood. Air pollution may be a nonspecific risk factor for the development of psychopathology.

Project description:ObjectiveIndividuals with 22q11.2 deletion syndrome are known to be at high risk of developing schizophrenia. Previous imaging studies have provided limited data on the relation of schizophrenia expression in 22q11.2 deletion syndrome to specific regional brain volumetric changes. The authors hypothesized that the main structural brain finding associated with schizophrenia expression in 22q11.2 deletion syndrome, as for schizophrenia in the general population, would be gray matter volumetric deficits, especially in the temporal lobes.MethodMR brain images from 29 patients with 22q11.2 deletion syndrome and schizophrenia and 34 comparison subjects with 22q11.2 deletion syndrome and no history of psychosis were analyzed using a voxel-based morphometry method that also yielded volumes for related region-of-interest analyses. The authors compared data from the two groups using an analysis of covariance model correcting for total intracranial volume, age, sex, IQ, and history of congenital cardiac defects. The false discovery rate threshold was set at 0.05 to account for multiple comparisons.ResultsVoxel-based morphometry analyses identified significant gray matter reductions in the left superior temporal gyrus (Brodmann's area 22) in the schizophrenia group. There were no significant between-group differences in white matter or CSF volumes. Region-of-interest analyses showed significant bilateral gray matter volume reductions in the temporal lobes and superior temporal gyri in the schizophrenia group.ConclusionsThe structural brain expression of schizophrenia associated with the highly penetrant 22q11.2 deletion involves lower gray matter volumes in temporal lobe regions. These structural MRI findings in a 22q11.2 deletion syndrome form of schizophrenia are consistent with those from studies involving schizophrenia samples from the general population. The results provide further support for 22q11.2 deletion syndrome as a genetic subtype and as a useful neurodevelopmental model of schizophrenia.

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

Publications

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

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