Autistic traits in youth with familial adenomatous polyposis: A Dutch-Canadian case-control study.

This study investigated the neurodevelopmental impact of pathogenic adenomatous polyposis coli (APC) gene variants in patients with familial adenomatous polyposis (FAP), a cancer predisposition syndrome. We hypothesized that certain pathogenic APC variants result in behavioral-cognitive challenges. We compared 66 FAP patients (cases) and 34 unaffected siblings (controls) to explore associations between APC variants and behavioral and cognitive challenges.

Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome.

This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS).

A Regional Burden of Sequence-Level Variation in the 22q11.2 Region Influences Schizophrenia Risk and Educational Attainment.

Background: Genomic loci where recurrent pathogenic copy number variants are associated with psychiatric phenotypes in the population may also be sensitive to the collective impact of multiple functional low-frequency single nucleotide variants (SNVs).

Methods: We examined the cumulative impact of low-frequency, functional SNVs within the 22q11.2 region on schizophrenia risk in a discovery cohort and an independent replication cohort (N = 1933 and N = 11,128, respectively), as well as the impact on educational attainment (EA) in a third, independent, general population cohort (N = 2081).

A normative chart for cognitive development in a genetically selected population.

Certain pathogenic genetic variants impact neurodevelopment and cause deviations from typical cognitive trajectories. Understanding variant-specific cognitive trajectories is clinically important for informed monitoring and identifying patients at risk for comorbid conditions. Here, we demonstrate a variant-specific normative chart for cognitive development for individuals with 22q11.

Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model.

Background: Genotype-first and within-family studies can elucidate factors that contribute to psychiatric illness. Combining these approaches, we investigated the patterns of influence of parental scores, a high-impact variant, and schizophrenia on dimensional neurobehavioral phenotypes implicated in major psychiatric disorders.

Methods: We quantitatively assessed cognitive (FSIQ, VIQ, PIQ), social, and motor functioning in 82 adult individuals with a 22q11.

Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11DS) is associated with a 20-25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline.

Impact of a 22q11.2 Microdeletion on Adult All-Cause Mortality in Tetralogy of Fallot Patients.

Background: Because of the importance of identifying factors that affect late outcomes in the increasing population of those with tetralogy of Fallot (TOF), we aimed to determine the effect of a 22q11.2 microdeletion on adult mortality, while accounting for pulmonary atresia, known to be enriched in 22q11.2 deletion syndrome (22q11.

A genetic model for multimorbidity in young adults.

Purpose: Multimorbidity is increasing in younger adults but is understudied in this population. We used 22q11.2 deletion syndrome (22q11.

The 22q11.2 deletion syndrome as a model for idiopathic scoliosis - A hypothesis.

Adolescent idiopathic scoliosis (AIS), defined as a lateral deviation of the spine of at least ten degrees, is a classic enigma in orthopaedics and affects 1-4% of the general population. Despite (over) a century of intensive research, the etiology is still largely unknown. One of the major problems in all existing AIS research is the fact that most patients come to medical attention after onset of the curve.

The Dutch Bipolar Offspring Study: Cognitive Development and Psychopathology.

Various aspects of the relationship between cognitive impairment and bipolar disorder are not clear yet. This study examines cognitive and educational functioning prospectively in offspring at familial risk for bipolar disorder, in order to improve our understanding of the association between cognitive functioning and psychopathology. Bipolar offspring (N = 92) from the prospective Dutch bipolar offspring study were evaluated at adolescence and adulthood for IQ estimate, educational achievement and development of any psychiatric disorder.

Low prevalence of substance use in people with 22q11.2 deletion syndrome.

Background: 22q11.2 deletion syndrome (22q11DS), one of the most common recurrent copy number variant disorders, is associated with dopaminergic abnormalities and increased risk for psychotic disorders.

Aims: Given the elevated prevalence of substance use and dopaminergic abnormalities in non-deleted patients with psychosis, we investigated the prevalence of substance use in 22q11DS, compared with that in non-deleted patients with psychosis and matched healthy controls.

Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects.

The 22q11.2 deletion syndrome is caused by non-allelic homologous recombination events during meiosis between low copy repeats (LCR22) termed A, B, C, and D. Most patients have a typical LCR22A-D (AD) deletion of 3 million base pairs (Mb).

Understanding the pediatric psychiatric phenotype of 22q11.2 deletion syndrome.

The purpose of this article is to provide an overview of current insights into the neurodevelopmental and psychiatric manifestations of 22q11.2 deletion syndrome (22q11DS) in children and adolescents. The pediatric neuropsychiatric expression of 22q11DS is characterized by high variability, both interindividual and intraindividual (different expressions over the lifespan).

Exploring the role of low-frequency and rare exonic variants in alcohol and tobacco use.

Background: Alcohol and tobacco use are heritable phenotypes. However, only a small number of common genetic variants have been identified, and common variants account for a modest proportion of the heritability. Therefore, this study aims to investigate the role of low-frequency and rare variants in alcohol and tobacco use.

White matter abnormalities in 22q11.2 deletion syndrome patients showing cognitive decline.

Background: Decline in cognitive functioning precedes the first psychotic episode in the course of schizophrenia and is considered a hallmark symptom of the disorder. Given the low incidence of schizophrenia, it remains a challenge to investigate whether cognitive decline coincides with disease-related changes in brain structure, such as white matter abnormalities. The 22q11.

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.

Explaining the variable penetrance of CNVs: Parental intelligence modulates expression of intellectual impairment caused by the 22q11.2 deletion.

The role of rare genetic variants, in particular copy number variants (CNVs), in the etiology of neurodevelopmental disorders is becoming increasingly clear. While the list of these disorder-related CNVs continues to lengthen, it has also become clear that in nearly all genetic variants the proportion of carriers who express the associated phenotype is far from 100%. To understand this variable penetrance of CNVs it is important to realize that even the largest CNVs represent only a tiny fraction of the entire genome.

Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome.

Importance: Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of 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.

BDNF Val66Met homozygosity does not influence plasma BDNF levels in healthy human subjects.

A putative pathway by which the BDNF Val66Met polymorphism (rs6265) leads to aberrant phenotypes is its influence on plasma BDNF. Research into the impact of rs6265 on plasma BDNF has given rise to conflicting results. Moreover, most such studies have compared Met-carriers with Val-homozygous subjects.

Expression of autism spectrum and schizophrenia in patients with a 22q11.2 deletion.

Background: Copy number variants (CNVs) associated with neuropsychiatric disorders are increasingly being identified. While the initial reports were relatively specific, i.e.

The association of the alpha-5 subunit of the nicotinic acetylcholine receptor gene and the brain-derived neurotrophic factor gene with different aspects of smoking behavior.

Recent studies show that different aspects of smoking behavior are associated with the α-5 subunit of the nicotinic acetylcholine receptor (CHRNA5) gene and the gene coding for brain-derived neurotrophic factor (BDNF). This raises the question whether the amount of cigarettes smoked per day has a different genetic background than smoking initiation and what other smoking phenotypes may be relevant. The aim of this study was to replicate these associations in a large population-based sample.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals.