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. METHOD: This cross-sectional study involved 434 patients with 22q11DS, 265 non-deleted patients with psychosis and 134 healthy controls. Psychiatric diagnosis, full-scale IQ and COMT Val158Met genotype were determined in the 22q11DS group. Substance use data were collected according to the Composite International Diagnostic Interview. RESULTS: The prevalence of total substance use (36.9%) and substance use disorders (1.2%), and weekly amounts of alcohol and nicotine use, in patients with 22q11DS was significantly lower than in non-deleted patients with psychosis or controls. Compared with patients with 22q11DS, healthy controls were 20 times more likely to use substances in general (P < 0.001); results were also significant for alcohol and nicotine use separately. Within the 22q11DS group, there was no relationship between the prevalence of substance use and psychosis or COMT genotype. Male patients with 22q11DS were more likely to use substances than female patients with 22q11DS. CONCLUSIONS: The results suggest that patients with 22q11DS are at decreased risk for substance use and substance use disorders despite the increased risk of psychotic disorders. Further research into neurobiological and environmental factors involved in substance use in 22q11DS is necessary to elucidate the mechanisms involved. DECLARATION OF INTEREST: None.

Serotonergic, noradrenergic and dopaminergic markers are related to cognitive function in adults with 22q11 deletion syndrome.

Patients with 22q11 deletion syndrome (22q11DS) have a high prevalence of psychiatric disorders and intellectual disability. At present the neurobiology underlying psychopathology in 22q11DS is still not understood. In the present study, we analyzed urinary serotonergic, dopaminergic and noradrenergic markers in 67 adults with 22q11DS. Levels of serotonin and the catecholamine metabolite homovanillic acid were significantly lower in the 22q11DS subjects compared to healthy controls. Within the 22q11DS group, levels of dopamine, homovanillic acid, norepinephrine, vanillyl mandelic acid and serotonin positively correlated with Full Scale Intelligence Quotient scores. Our results suggest that cognitive deficits in 22q11DS are associated with abnormal function of several neurotransmitters.

Evaluation of the use of a specially designed saw to remove penis rings at the emergency department.

Objective: Penile strangulation is a rising problem in emergency departments (ED) and can cause serious medical issues. The removal of a penile ring requires immediate action, but is a difficult task. In this study an in-house specialised designed saw to safely remove penis rings is evaluated. Materials and Methods: To evaluate the use of the penis ring saw we used information from our maintenance management software to evaluate the amount of malfunctions. The evaluation of the experiences in the ED were based on semi-structured interviews with ED employees and with the mechanical engineers that developed and maintain the saw. Results: Since 2013 seven jobs were found regarding to a defect of the saw. All defects were broken saw blades. Four emergency care department employees and two instrumentmakers were interviewed. All four are pleased with the saw, because it improves patient safety during removal of the penis ring. The two instrument makers agree with the ED nurses that the saw is an improvement compared to the previous used solutions. Possible improvements were also suggested. Conclusion: A specialized saw was designed and developed for the removal of penis rings. This saw offers a safe and standardized way to remove the penis rings.

Glutamatergic markers, age, intellectual functioning and psychosis in 22q11 deletion syndrome.

RATIONALE: Patients with 22q11 deletion syndrome (22q11DS) have a high prevalence of intellectual disabilities and psychiatric disorders, including psychosis. Haplo-insufficiency of genes in the deleted region may offer a partial explanation for the increased vulnerability for psychosis and intellectual disability. One gene of particular interest is the gene coding for proline dehydrogenase (PRODH), an enzyme responsible for the conversion of proline into glutamate. OBJECTIVES: Because abnormalities in glutamatergic signaling are thought to be responsible for cognition and psychosis in the general population, we hypothesized that PRODH haplo-insufficiency may underlie some of the cognitive and psychotic features seen in 22q11DS. METHODS: In this explorative study, we investigated the relation between plasma proline, glutamate, and glutamine and age, intelligence, and psychosis in 64 adults with 22q11DS. RESULTS: Hyperprolinemia was found in 31.3% of subjects with 22q11DS. A relation between glutamine, glutamate, proline, and presence of psychosis was not observed. Regression analysis revealed a positive relation between plasma glutamate and age, a positive relation of glutamate with antipsychotic drugs, a relation of glutamine and gender, and a positive relation of glutamine and mood stabilizing drugs, and a negative relation of the ratio glutamine/glutamate and age. The group with relatively lower IQ had higher glutamate levels compared to the group with relatively higher IQ. CONCLUSIONS: Our results suggest that 22q11DS is accompanied by abnormalities in glutamatergic metabolism. Future longitudinal studies are needed to further investigate the glutamatergic system in 22q11DS and how this affects the development of cognitive problems and psychopathology.

Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome.

OBJECTIVE: Chromosome 22q11.2 deletion syndrome is a neurogenetic disorder associated with high rates of schizophrenia and other psychiatric conditions. The authors report what is to their knowledge the first large-scale collaborative study of rates and sex distributions of psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome. The associations among psychopathology, intellect, and functioning were examined in a subgroup of participants. METHOD: The 1,402 participants with 22q11.2 deletion syndrome, ages 6­68 years, were assessed for psychiatric disorders with validated diagnostic instruments. Data on intelligence and adaptive functioning were available for 183 participants ages 6 to 24 years. RESULTS: Attention deficit hyperactivity disorder (ADHD) was the most frequent disorder in children (37.10%) and was overrepresented in males. Anxiety disorders were more prevalent than mood disorders at all ages, but especially in children and adolescents. Anxiety and unipolar mood disorders were overrepresented in females. Psychotic disorders were present in 41% of adults over age 25. Males did not predominate in psychotic or autism spectrum disorders. Hierarchical regressions in the subgroup revealed that daily living skills were predicted by the presence of anxiety disorders. Psychopathology was not associated with communication or socialization skills. CONCLUSIONS: To the authors' knowledge, this is the largest study of psychiatric morbidity in 22q11.2 deletion syndrome. It validates previous findings that this condition is one of the strongest risk factors for psychosis. Anxiety and developmental disorders were also prevalent. These results highlight the need to monitor and reduce the long-term burden of psychopathology in 22q11.2 deletion syndrome.