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.

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.