Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6–1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin

A cognitive decline precedes the onset of psychosis in patients with the 22q11.2 deletion syndrome

Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk for developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities, starting at a young age

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present

Behavioral phenotype in children with 22q11Ds : Agreement between parents and teachers

Patients with the 22q11-deletion syndrome (22q11DS) are at an increased risk of developing schizophrenia. Besides the effects of genetic variation, environmental factors could also be important in modifying the risk of schizophrenia in 22q11DS patients. In particular, previous studies have shown the importance of stress as a precipitating factor of psychosis. An incongruence between the perceived and actual severity of behavioral and cognitive domains could lead caregivers, and even the children themselves, to make demands that are insufficiently adapted to the child's abilities, causing stress and anxiety. Here, we investigate whether such diagnostic discrepancies are indeed present by comparing parent and teacher reports on behavioral concerns in children with 22q11DS. Behavioral questionnaires (CBCL and TRF) were prepared for both parents and teachers of 146 children with 22q11DS. We found that in line with previous reports, internalizing behavior was more frequently reported than externalizing behavior. While the behavioral profiles reported by parents and teachers were remarkably similar, the teachers' ratings were significantly lower (Total problem score p = .002). Age and IQ were not significantly associated with the severity of reported concerns. Our results indicate that indeed a disparity often exists between parents' and teachers' perceptions of the severity of a child's behavioral deficits. This may result in (substantially) different demands and expectations being placed on the child from the two fronts. We speculate that the stress resulting from this lack of cohesion between parents and teachers could precipitate, at least in some 22q11DS children, the emergence of psychosis

Implementing “Online Communities” for pregnant women in times of COVID-19 for the promotion of maternal well-being and mother-to-infant bonding:a pretest–posttest study

Background: The Coronavirus Disease 2019 (COVID-19) pandemic elevated the risk for mental health problems in pregnant women, thereby increasing the risk for long-term negative consequences for mother and child well-being. There was an immediate need for easily accessible interventions for pregnant women experiencing elevated levels of pandemic related stress. Methods: A three-session intervention “Online Communities” (OC) was developed at the beginning of the Dutch lockdown, and implemented by a team of midwives and psychologists specialized in Infant Mental Health. Pretest (N = 34) and posttest (N = 17) measurements of depressive symptoms, worries about COVID-19 and worries in general, and mother-to-infant bonding were administered, as well as a posttest evaluation. Results: At pretest, the OC group was compared to two reference groups of pregnant women from an ongoing pregnancy cohort study: a COVID-19 (N = 209) and pre-COVID-19 reference group (N = 297). OC participants had significantly more depressive symptoms than both reference groups, and less positive feelings of bonding than the COVID-19 but not the pre-COVID-19 reference group. Compared to pretest, significant decreases in depressive symptoms (with significantly less participants scoring above cut-off) and worries about COVID-19 (large effect sizes) and worries in general (moderate to large effect size) were found at posttest for the OC participants. No significant improvement was found in bonding. Participants rated the intervention positively. Conclusions: The current study provides initial evidence supporting the idea that OC is a promising and readily accessible intervention for pregnant women experiencing stress due to the COVID-19 pandemic, and possibly also applicable to other stressors. Trial registration: This intervention was registered in the Netherlands Trial Registration (registration number Trial NL8842, registration date 18/08/2020)

Implementing "Online Communities" for pregnant women in times of COVID-19 for the promotion of maternal well-being and mother-to-infant bonding: A pretest-posttest study

Background:  The Coronavirus Disease 2019 (COVID-19) pandemic elevated the risk for mental health problems in pregnant women, thereby increasing the risk for long-term negative consequences for mother and child well-being. There was an immediate need for easily accessible interventions for pregnant women experiencing elevated levels of pandemic related stress. Methods:  A three-session intervention "Online Communities" (OC) was developed at the beginning of the Dutch lockdown, and implemented by a team of midwives and psychologists specialized in Infant Mental Health. Pretest (N = 34) and posttest (N = 17) measurements of depressive symptoms, worries about COVID-19 and worries in general, and mother-to-infant bonding were administered, as well as a posttest evaluation. Results:  At pretest, the OC group was compared to two reference groups of pregnant women from an ongoing pregnancy cohort study: a COVID-19 (N = 209) and pre-COVID-19 reference group (N = 297). OC participants had significantly more depressive symptoms than both reference groups, and less positive feelings of bonding than the COVID-19 but not the pre-COVID-19 reference group. Compared to pretest, significant decreases in depressive symptoms (with significantly less participants scoring above cut-off) and worries about COVID-19 (large effect sizes) and worries in general (moderate to large effect size) were found at posttest for the OC participants. No significant improvement was found in bonding. Participants rated the intervention positively. Conclusions:  The current study provides initial evidence supporting the idea that OC is a promising and readily accessible intervention for pregnant women experiencing stress due to the COVID-19 pandemic, and possibly also applicable to other stressors. Trial registration: This intervention was registered in the Netherlands Trial Registration (registration number Trial NL8842 , registration date 18/08/2020)

Early interventions in risk groups for schizophrenia : what are we waiting for?

Intervention strategies in adolescents at ultra high-risk (UHR) for psychosis are promising for reducing conversion to overt illness, but have only limited impact on functional outcome. Recent studies suggest that cognition does not further decline during the UHR stage. As social and cognitive impairments typically develop before the first psychotic episode and even years before the UHR stage, prevention should also start much earlier in the groups at risk for schizophrenia and other psychiatric disorders. Early intervention strategies could aim to improve stress resilience, optimize brain maturation, and prevent or alleviate adverse environmental circumstances. These strategies should urgently be tested for efficacy: the prevalence of ~1% implies that yearly ~22 in every 100,000 people develop overt symptoms of this illness, despite the fact that for many of them-e.g., children with an affected first-degree family member or carriers of specific genetic variants-increased risk was already identifiable early in life. Our current ability to recognize several risk groups at an early age not only provides an opportunity, but also implies a clinical imperative to act. Time is pressing to investigate preventive interventions in high-risk children to mitigate or prevent the development of schizophrenia and related psychiatric disorders