Mental health, coping, and protective factors in mothers of children with 22q11.2 deletion syndrome.

Compared to the large body of maternal mental health research for other pediatric disorders, we know far less about the experience of mothers of children with 22q11DS. This study investigates the coping methods, protective factors, and mental health of this population. These findings might lead to better support for 22q11DS maternal mental health. An international sample of 71 mothers (M = 40.5 years) of children with 22q11DS (M = 9.2 years) was recruited and completed an online survey assessing maternal mental health (symptoms of depression, anxiety, traumatic stress, general stress, and alcohol consumption), coping methods, and mental health protective factors (social support, dyadic adjustment, parenting competence). Maternal ratings of child mental health symptoms were also obtained. Mothers' self-report revealed a high percentage who screened positive for elevated levels of general stress (69%), hazardous alcohol consumption (30.9%), traumatic stress (33.8%), anxiety (26.8%), and depression (26.8%). After controlling for demographic variables and child mental health symptoms, maternal self-reported maladaptive coping methods were positively associated with maternal symptoms of depression, anxiety, stress, and traumatic stress. Reducing maladaptive coping methods may be a promising intervention for improving mental health in mothers of children with 22q11DS.

DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion.

BACKGROUND: Dendritic spines are the sites of excitatory synapses on pyramidal neurons, and their development is crucial for neural circuits and brain functions. The spine shape, size, or number alterations are associated with neurological disorders, including schizophrenia. DiGeorge syndrome critical region gene 2 (DGCR2) is one of the deleted genes within the 22q11.2 deletion syndrome (22q11DS), which is a high risk for developing schizophrenia. DGCR2 expression was reduced in schizophrenics. However, the pathophysiological mechanism of DGCR2 in schizophrenia or 22q11DS is still unclear. RESULTS: Here, we report that DGCR2 expression was increased during the neurodevelopmental period and enriched in the postsynaptic densities (PSDs). DGCR2-deficient hippocampal neurons formed fewer spines. In agreement, glutamatergic transmission and synaptic plasticity were decreased in the hippocampus of DGCR2-deficient mice. Further molecular studies showed that the extracellular domain (ECD) of DGCR2 is responsible for its transcellular interaction with cell adhesion molecule Neurexin1 (NRXN1) and spine development. Consequently, abnormal behaviors, like anxiety, were observed in DGCR2-deficient mice. CONCLUSIONS: These observations indicate that DGCR2 is a novel cell adhesion molecule required for spine development and synaptic plasticity, and its deficiency induces abnormal behaviors in mice. This study provides a potential pathophysiological mechanism of DGCR2 in 22q11DS and related mental disorders.

Quantifying the resolution of spatial and temporal representation in children with 22q11.2 deletion syndrome.

OBJECTIVES: Our ability to generate mental representation of magnitude from sensory information affects how we perceive and experience the world. Reduced resolution of the mental representations formed from sensory inputs may generate impairment in the proximal and distal information processes that utilize these representations. Impairment of spatial and temporal information processing likely underpins the non-verbal cognitive impairments observed in 22q11.2 deletion syndrome (22q11DS). The present study builds on prior research by seeking to quantify the resolution of spatial and temporal representation in children with 22q11DS, sex chromosome aneuploidy (SCA), and a typically developing (TD) control group. PARTICIPANTS AND METHODS: Children (22q11DS = 70, SCA = 49, TD = 46) responded to visual or auditory stimuli with varying difference ratios. The participant's task was to identify which of two sequentially presented stimuli was of larger magnitude in terms of, size, duration, or auditory frequency. Detection threshold was calculated as the minimum difference ratio between the "standard" and the "target" stimuli required to achieve 75% accuracy in detecting that the two stimuli were different. RESULTS: Children with 22q11DS required larger magnitude difference between spatial stimuli for accurate identification compared with both the SCA and TD groups (% difference from standard: 22q11DS = 14; SCA = 8; TD: 7; F = 8.42, p < 0.001). Temporal detection threshold was also higher for the 22q11DS group to both visual (% difference from standard: 22q11DS = 14; SCA = 8; TD = 7; F = 8.33, p < 0.001) and auditory (% difference from standard: 22q11DS = 23; SCA = 12; TD: 8; F = 8.99, p < 0.001) stimuli compared with both the SCA and TD groups, while the SCA and TD groups displayed equivalent performance on these measures (p's > 0.05). Pitch detection threshold did not differ among the groups (p's > 0.05). CONCLUSIONS: The observation of higher detection thresholds to spatial and temporal stimuli indicates further evidence for reduced resolution in both spatial and temporal magnitude representation in 22q11DS, that does not extend to frequency magnitude representation (pitch detection), and which is not explained by generalized cognitive impairment alone. These findings generate further support for the hypothesis that spatiotemporal hypergranularity of mental representations contributes to the non-verbal cognitive impairment seen in 22q11DS.

Predicting Cognition and Psychosis in Young Adults With 22q11.2 Deletion Syndrome.

OBJECTIVE: To assess the extent to which the trajectories of intellectual, academic achievement, executive functioning, attention, working memory, and emotion recognition tests will be predictive of psychosis in young adults with 22q11.2 deletion syndrome (22q11DS). METHODS: Eighty-two participants with 22q11DS were assessed for psychiatric disorders and neuropsychological functioning with validated instruments. Siblings and community controls were employed as comparison groups. RESULTS: Individuals with 22q11DS differed significantly from siblings and controls in longitudinal trajectories of visual and auditory working memory as well as academic achievement. Longitudinal trajectories of cognitive set shifting, reading decoding, and emotion recognition predicted the presence of positive symptoms of psychosis in early adulthood. Cognitive set shifting improved at a slower rate for individuals with 22q11DS + psychosis than those without psychosis. Emotion recognition increased steadily in individuals without psychosis, whereas for those with psychosis, scores increased until approximately 15 years of age, at which point they began to decrease rapidly. A similar, but more subtle effect, was seen for reading decoding. CONCLUSIONS: Our data are the first to go beyond IQ assessments in assessing longitudinal neuropsychological outcomes and risk for psychosis in 22q11DS. Individuals with 22q11DS who developed psychotic symptoms improved less appreciably and continued to demonstrate difficulties with cognitive flexibility relative to individuals with 22q11DS who did not have psychotic symptoms. Individuals with 22q11DS who developed psychosis had weaker reading skills in childhood and, after an initial improvement into adolescence, these individuals with psychosis had a decline in reading skills. In 22q11DS, cognitive deficits are both (a) traits that are preexisting and raise the risk for psychosis and (b) associated with the onset of psychotic symptoms. Future research should consider the extent to which cognitive set shifting and reading decoding are related to the Verbal IQ declines observed in the 22q11DS population.

Prevalence and treatment of psychiatric disorders other than psychosis in children and adolescents with 22q11DS: Examining associations with social and role functioning.

Individuals with chromosome 22q11 deletion syndrome (22q11DS) have high rates of psychotic disorders. Less is known about their psychopathology and how it is treated prior to the peak period of risk for psychotic disorder. There is also a lack of evidence on how functioning is impacted by psychopathology in this population. The aim of this study was to investigate the prevalence and treatment of non-psychotic psychiatric disorders, and how these factors are associated with psychosocial functioning in children and adolescents with 22q11DS. 126 individuals with 22q11DS aged 8-17 participated in the study. Participants were assessed for psychiatric diagnoses, social and role functioning, anxiety and depressive symptoms and IQ. Information on current treatments was collected. 52.4% of the sample presented with at least one psychiatric disorder. Mood and anxiety disorders were the most frequent, followed by behavioural disorder. Individuals with a psychiatric disorder had significantly lower general, role and social functioning. Only 27% of participants with a psychiatric diagnosis were receiving any mental health treatment at the time of assessment. Findings suggest the high prevalence of psychiatric disorders in youth with 22q11DS, which significantly impacts psychosocial functioning. Despite this, psychiatric disorders tend to remain untreated in this population.

Abnormalities in brain white matter in adolescents with 22q11.2 deletion syndrome and psychotic symptoms.

BACKGROUND: 22q11.2 Deletion Syndrome (22q11DS) is considered to be a promising cohort to explore biomarkers of schizophrenia risk based on a 30 % probability of developing schizophrenia in adulthood. In this study, we investigated abnormalities in the microstructure of white matter in adolescents with 22q11DS and their specificity to prodromal symptoms of schizophrenia. METHODS: Diffusion Magnetic Resonance Imaging (dMRI) data were acquired from 50 subjects with 22q11DS (9 with and 41 without prodromal psychotic symptoms), and 47 matched healthy controls (mean age 18 +/-2 years). DMRI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and compared between groups using the Tract Based Spatial Statistics (TBSS) method. Additionally, correlations between dMRI measures and scores on positive symptoms were performed. RESULTS: Reductions in MD, AD and RD (but not FA) were found in the corpus callosum (CC), left and right superior longitudinal fasciculus (SLF), and left and right corona radiata in the entire 22q11DS group. In addition, the 22q11DS subgroup with prodromal symptoms showed reductions in AD and MD, but no changes in RD when compared to the non-prodromal subgroup, in CC, right SLF, right corona radiata and right internal capsule. Finally, AD values in these tracts correlated with the scores on the psychosis subscale. CONCLUSION: Microstructural abnormalities in brain white matter are present in adolescent subjects with prodromal psychotic symptoms.

Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition.

BACKGROUND: People with 22q11.2 deletion syndrome (22q11DS) have difficulty processing social information including facial identity and emotion processing. However, difficulties with visual and attentional processes may play a role in difficulties observed with these social cognitive skills. METHODS: A cross-sectional study investigated visual perception and processing as well as facial processing abilities in a group of 49 children and adolescents with 22q11DS and 30 age and socio-economic status-matched healthy sibling controls using the Birmingham Object Recognition Battery and face processing sub-tests from the MRC face processing skills battery. RESULTS: The 22q11DS group demonstrated poorer performance on all measures of visual perception and processing, with greatest impairment on perceptual processes relating to form perception as well as object recognition and memory. In addition, form perception was found to make a significant and unique contribution to higher order social-perceptual processing (face identity) in the 22q11DS group. CONCLUSIONS: The findings indicate evidence for impaired visual perception and processing capabilities in 22q11DS. In turn, these were found to influence cognitive skills needed for social processes such as facial identity recognition in the children with 22q11DS.

An fMRI study of facial emotion processing in children and adolescents with 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11DS, velo-cardio-facial syndrome [VCFS]) is a genetic disorder associated with interstitial deletions of chromosome 22q11.2. In addition to high rates of neuropsychiatric disorders, children with 22q11DS have impairments of face processing, as well as IQ-independent deficits in visuoperceptual function and social and abstract reasoning. These face-processing deficits may contribute to the social impairments of 22q11DS. However, their neurobiological basis is poorly understood. METHODS: We used event-related functional magnetic resonance imaging (fMRI) to examine neural responses when children with 22q11DS (aged 9-17 years) and healthy controls (aged 8-17 years) incidentally processed neutral expressions and mild (50%) and intense (100%) expressions of fear and disgust. We included 28 right-handed children and adolescents: 14 with 22q11DS and 14 healthy (including nine siblings) controls. RESULTS: Within groups, contrasts showed that individuals significantly activated 'face responsive' areas when viewing neutral faces, including fusiform-extrastriate cortices. Further, within both groups, there was a significant positive linear trend in activation of fusiform-extrastriate cortices and cerebellum to increasing intensities of fear. There were, however, also between-group differences. Children with 22q11DS generally showed reduced activity as compared to controls in brain regions involved in social cognition and emotion processing across emotion types and intensities, including fusiform-extrastriate cortices, anterior cingulate cortex (Brodmann area (BA) 24/32), and superomedial prefrontal cortices (BA 6). Also, an exploratory correlation analysis showed that within 22q11DS children reduced activation was associated with behavioural impairment-social difficulties (measured using the Total Difficulties Score from the Strengths and Difficulties Questionnaire [SDQ]) were significantly negatively correlated with brain activity during fear and disgust processing (respectively) in the left precentral gyrus (BA 4) and in the left fusiform gyrus (FG, BA 19), right lingual gyrus (BA 18), and bilateral cerebellum. CONCLUSIONS: Regions involved in face processing, including fusiform-extrastriate cortices, anterior cingulate gyri, and superomedial prefrontal cortices (BA 6), are activated by facial expressions of fearful, disgusted, and neutral expressions in children with 22q11DS but generally to a lesser degree than in controls. Hypoactivation in these regions may partly explain the social impairments of children with 22q11DS.