Background: 22q11 Deletion Syndrome (22q11DS) is the most common microdeletion syndrome with broad phenotypic variability, leading to significant morbidity and some mortality. The varied health problems associated with 22q11DS and the evolving phenotype (both medical and developmental/behavioural) across the lifespan can strongly impact the mental health of patients as well as their caregivers. Like caregivers of children with other chronic diseases, caregivers of children with 22q11DS may experience an increased risk of traumatisation and mental health symptoms.Objective: The study\'s primary objective was to assess the frequency of traumatic experiences and mental health symptoms among mothers of children with 22q11DS. The secondary objective was to compare their traumatic experiences to those of mothers of children with other neurodevelopmental disorders (NDDs).Method: A total of 71 mothers of children diagnosed with 22q11DS completed an online survey about their mental health symptoms and traumatic experiences. Descriptive statistics were used to summarise the prevalence of their mental health symptoms and traumatic experiences. Logistic regression models were run to compare the traumatic experiences of mothers of children with 22q11DS to those of 335 mothers of children with other neurodevelopmental disorders (NDDs).Results: Many mothers of children with 22q11DS experienced clinically significant mental health symptoms, including depression (39%), anxiety (25%), and post-traumatic stress disorder (PTSD) symptoms (30%). The types of traumatic events experienced by mothers of children with 22q11DS differed from those of mothers of children with other NDDs as they were more likely to observe their child undergoing a medical procedure, a life-threatening surgery, or have been with their child in the intensive care unit.Conclusion: 22q11DS caregivers are likely to require mental health support and trauma-informed care, tailored to the specific needs of this population as they experience different kinds of traumatic events compared to caregivers of children with other NDDS.
Mothers of children with 22q11DS experience clinically significant levels of depression, anxiety, and PTSD.Mothers of children with 22q11DS experience many and diverse trauma particularly related to medical interventions of their child.The types of traumatic events experienced by mothers of children with 22q11DS are different from those of the mothers of children with other neurodevelopmental disorders.

Schizophrenia is a complex multi-factor neurological disorder that caused an array of severe indelible consequences to the individuals and society. Additionally, anti-schizophrenic drugs are unsuitable for treating negative symptoms and have more significant side effects and drug resistance. For better treatment and prevention, we consider exploring the pathogenesis of schizophrenia from other perspectives. A growing body of evidence of 22q11.2 deletion syndrome (22q11DS) suggested that the occurrence and progression of schizophrenia are related to mitochondrial dysfunction. So combing through the literature of 22q11DS published from 2000 to 2023, this paper reviews the mechanism of schizophrenia based on mitochondrial dysfunction, and it focuses on the natural drugs targeting mitochondria to enhance mitochondrial function, which are potential to improve the current treatment of schizophrenia.

Executive functioning (EF) is an umbrella term for various cognitive functions that play a role in monitoring and planning to effectuate goal-directed behavior. The 22q11.2 deletion syndrome (22q11DS), the most common microdeletion syndrome, is associated with a multitude of both somatic and cognitive symptoms, including EF impairments in school-age and adolescence. However, results vary across different EF domains and studies with preschool children are scarce. As EF is critically associated with later psychopathology and adaptive functioning, our first aim was to study EF in preschool children with 22q11DS. Our second aim was to explore the effect of a congenital heart defects (CHD) on EF abilities, as CHD are common in 22q11DS and have been implicated in EF impairment in individuals with CHD without a syndromic origin.
All children with 22q11DS (n = 44) and typically developing (TD) children (n = 81) were 3.0 to 6.5 years old and participated in a larger prospective study. We administered tasks measuring visual selective attention, visual working memory, and a task gauging broad EF abilities. The presence of CHD was determined by a pediatric cardiologist based on medical records.
Analyses showed that children with 22q11DS were outperformed by TD peers on the selective attention task and the working memory task. As many children were unable to complete the broad EF task, we did not run statistical analyses, but provide a qualitative description of the results. There were no differences in EF abilities between children with 22q11DS with and without CHDs.
To our knowledge, this is the first study measuring EF in a relatively large sample of young children with 22q11DS. Our results show that EF impairments are already present in early childhood in children with 22q11DS. In line with previous studies with older children with 22q11DS, CHDs do not appear to have an effect on EF performance. These findings might have important implications for early intervention and support the improvement of prognostic accuracy.

22q11.2 deletion syndrome (22q11DS) is a clinically heterogeneous genetic syndrome, associated with a wide array of neuropsychiatric symptoms. The clinical presentation is likely to be influenced by environmental factors, yet little is known about this. Here, we review the available research literature on the role of the environment in 22q11DS. We find that within-patient design studies have mainly investigated the role of parental factors, stress, and substance use, reporting significant effects of these factors on the clinical profile. Case-control studies have been less successful, with almost no reports of significant moderating effects of the environment. We go on to hypothesize which specific environmental measures are most likely to interact with the 22q11 deletion, based on the genes in this region and their involvement in molecular pathways. We end by discussing potential reasons for the limited findings so far, including modest sample sizes and limited availability of environmental measures, and make recommendations how to move forward.

Numerous behavioral studies have highlighted the contribution of visual perceptual deficits to the nonverbal cognitive profile of individuals with 22q11.2 deletion syndrome. However, the neurobiological processes underlying these widespread behavioral alterations are yet to be fully understood. Thus, in this paper, we investigated the role of neural oscillations toward visuoperceptual deficits to elucidate the neurobiology of sensory impairments in deletion carriers.
We acquired 125 high-density electroencephalography recordings during a visual grating task in a group of 62 deletion carriers and 63 control subjects. Stimulus-elicited oscillatory responses were analyzed with 1) time-frequency analysis using wavelets decomposition at sensor and source level, 2) intertrial phase coherence, and 3) Granger causality connectivity in source space. Additional analyses examined the development of neural oscillations across age bins.
Deletion carriers had decreased theta-band (4-8 Hz) and gamma-band (58-68 Hz) spectral power compared with control subjects in response to the visual stimuli, with an absence of age-related increase of theta- and gamma-band responses. Moreover, adult deletion carriers had decreased gamma- and theta-band responses but increased alpha/beta desynchronization (10-25 Hz) that correlated with behavioral performance. Granger causality estimates reflected an increased frontal-occipital connectivity in the beta range (22-40 Hz).
Deletion carriers exhibited decreased theta- and gamma-band responses to visual stimuli, while alpha/beta desynchronization was preserved. Overall, the lack of age-related changes in deletion carriers implicates developmental impairments in circuit mechanisms underlying neural oscillations. The dissociation between the maturation of theta/gamma- and alpha/beta-band responses may indicate a selective impairment in supragranular cortical layers, leading to compensatory top-down connectivity.

OBJECTIVE: Brain oscillations play a pivotal role in synchronizing responses of local and global ensembles of neurons. Patients with schizophrenia exhibit impairments in oscillatory response, which are thought to stem from abnormal maturation during critical developmental stages. Studying individuals at genetic risk for psychosis, such as 22q11.2 deletion carriers, from childhood to adulthood may provide insights into developmental abnormalities.
METHODS: The authors acquired 106 consecutive T1-weighted MR images and 40-Hz auditory steady-state responses (ASSRs) with high-density (256 channel) EEG in a group of 58 22q11.2 deletion carriers and 48 healthy control subjects. ASSRs were analyzed with 1) time-frequency analysis using Morlet wavelet decomposition, 2) intertrial phase coherence (ITPC), and 3) theta-gamma phase-amplitude coupling estimated in the source space between brain regions activated by the ASSRs. Additionally, volumetric analyses were performed with FreeSurfer. Subanalyses were conducted in deletion carriers who endorsed psychotic symptoms and in subgroups with different age bins.
RESULTS: Deletion carriers had decreased theta and late-latency 40-Hz ASSRs and phase synchronization compared with control subjects. Deletion carriers with psychotic symptoms displayed a further reduction of gamma-band response, decreased ITPC, and decreased top-down modulation of gamma-band response in the auditory cortex. Reduced gamma-band response was correlated with the atrophy of auditory cortex in individuals with psychotic symptoms. In addition, a linear increase of theta and gamma power from childhood to adulthood was found in control subjects but not in deletion carriers.
CONCLUSIONS: The results suggest that while all deletion carriers exhibit decreased gamma-band response, more severe local and long-range communication abnormalities are associated with the emergence of psychotic symptoms and gray matter loss. Additionally, the lack of age-related changes in deletion carriers indexes a potential developmental impairment in circuits underlying the maturation of neural oscillations during adolescence. The progressive disruption of gamma-band response in 22q11.2 deletion syndrome supports a developmental perspective toward understanding and treating psychotic disorders.

This study examined the associations of parents\' expressed emotion (EE) and parenting stress, with behavioral problems of children with 22q11.2 deletion syndrome, idiopathic autism (iASD) and typically developing (TD) children. Parents of children aged 3-8 years completed the five-minute-speech-sample (FMSS), parental stress index and children behavioral checklist. Parents\' FMSS-EE-criticism was higher among parents of children with 22q11DS and iASD compared to parents of TD children. FMSS-EE scores predicted children\'s behavioral problems, above and beyond parenting stress. The associations between FMSS-EE, parenting stress and children\'s behavioral problems were consistent across 22q11DS, iASD and TD children. These findings highlight the need for targeting parents\' EE and parenting stress as integral elements in the screening and prevention of behavioral problems of young children with 22q11DS and iASD.

22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental disorder that represents one of the greatest known risk factors for psychosis. Previous studies in psychotic subjects without the deletion have identified a dopaminergic dysfunction in striatal regions, and dysconnectivity of striatocortical systems, as an important mechanism in the emergence of psychosis. Here, we used resting-state functional MRI to examine striatocortical functional connectivity in 22q11.2DS patients. We used a 2 × 2 factorial design including 125 subjects (55 healthy controls, 28 22q11.2DS patients without a history of psychosis, 10 22q11.2DS patients with a history of psychosis, and 32 subjects with a history of psychosis without the deletion), allowing us to identify network effects related to the deletion and to the presence of psychosis. In line with previous results from psychotic patients without 22q11.2DS, we found that there was a dorsal to ventral gradient of hypo- to hyperstriatocortical connectivity related to psychosis across both patient groups. The 22q11.2DS was additionally associated with abnormal functional connectivity in ventral striatocortical networks, with no significant differences identified in the dorsal system. Abnormalities in the ventral striatocortical system observed in these individuals with high genetic risk to psychosis may thus reflect a marker of illness risk.

Chromosome 22q11.2 deletion syndrome (22q11DS) is characterised by a complex behavioural phenotype including anxiety, attention-deficit/hyperactivity disorder and psychosis. In the current study, we aimed at improving our understanding of the heterogeneity of behavioural characteristics in a group of 129 young people (aged 4-22) with a confirmed 22q11.2 microdeletion and 116 age and gender matched typically developing controls. Half the participants with 22q11DS had behaviour characterised by emotion dysregulation. A cluster analyses, of the participants with 22q11DS, revealed four groups characterised by intact emotion regulation; predominantly internalizing problems; both internalizing and externalizing problems; and predominantly externalizing difficulties. Importantly, it was found that young people with 22q11DS whose emotion dysregulation was characterised by externalizing problems had the poorest levels of functioning. As our understanding of 22q11DS improves, it is becoming increasingly clear that we need a better understanding of how individual differences and psychosocial factors contribute to, and interact with one another, to result in the observable individual differences in the 22q11DS behavioural phenotype.

The study aimed at assessing the relationship between skull base morphology, represented by skull base and nasopharyngeal angles, and palatal anatomy among patients with 22q11DS and velopharyngeal dysfunction. Retrospective analysis of patients with 22q11DS and velopharyngeal dysfunction. Age, sex, severity of velopharyngeal dysfunction, type of cleft (overt cleft palate, submucous cleft palate, occult submucous cleft palate, or no-CP, and cephalometric skull base angles were reviewed. Correlations between type of palatal anomaly and the angles were assessed. Among 132 patients, 71 were male (53.8%) and 61 were female (46.2%), ages 3.3-40.0 years (mean 8.3 ± 6.10). No difference in the mean cranial-base angle (P = 0.353) or in the distribution of the three types of cranial base angle sizes was found among the palatal anomaly groups (P = 0.137). More men had normal cranial base angles and more women had acute angulation (P = 0.008). A positive correlation was found between the skull base and nasopharyngeal angles (P = 0.001, r = -0.590). No direct correlation was found between cranial base morphology and palatal anomalies in patients with 22q11DS, and velopharyngeal dysfunction. This is probably because skull base and palate morphology contribute independently to velopharyngeal dysfunction.