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Schizophrenia Looms Large in International 22q11.2 Deletion Survey

July 3, 2014. The largest survey to date of people with 22q11.2 deletions found that schizophrenia spectrum disorders afflicted 41 percent of those 25 and older, and that attention deficit hyperactivity disorder (ADHD) was diagnosed in 37 percent of children. The report, published in the American Journal of Psychiatry on June 1, catalogues the psychiatric features of 1,402 people aged six to 68 years old with 22q11.2 deletions.

The survey comes from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome, a collaboration spanning 15 sites in Europe, North America, the Middle East, and Australia. Deletions of 22q11.2 are rare, so the consortium pooled their samples to come up with better estimates of the prevalence of psychiatric disorders in this population. The findings argue that awareness and early treatment of these conditions should be part of the clinical management of people with 22q11.2 deletions.

People with 22q11.2 deletions are missing one copy of about 45 genes, leading to a range of symptoms that include heart defects, facial anomalies, and cognitive impairments, though people typically differ in symptom profile and severity. Researchers have focused on the genes in this region to understand the molecular etiology of schizophrenia (see SRF related news report), which at least one-quarter of people with 22q11.2 deletions develop. The new survey suggests that the deletion elevates risk for schizophrenia even higher, as it does for other psychiatric conditions, including ADHD and anxiety.

Psychiatric prevalence
First author Maude Schneider of the University of Geneva, Switzerland, and colleagues combined data from 15 different sites around the world. The sites differed in how people with 22q11.2 came to their attention, but they had all been assessed with standard psychiatric tools, though the specific tool differed among sites. Study participants were grouped according to their age, making the survey a cross-sectional one.

The prevalence for any schizophrenia spectrum disorder (not including bipolar with psychosis) increased across each age group. For example, among emerging adults (18-25 years), 24 percent had a diagnosis of a schizophrenia spectrum disorder, but this jumped to 41 percent in young adults (26-35 years) and 42 percent in mature adults over 36 years old. In each age group, the bulk of these cases had a diagnosis of schizophrenia. Even 10 percent of adolescents (13-17 years) qualified for a diagnoses of a schizophrenia spectrum disorder.

Anxiety disorders featured even more consistently across the lifespan, as it was diagnosed in 36 percent of children (6-12 years), 34 percent of adolescents (13-17 years), and about a quarter of people in the emerging, young, and mature adult groups. The specific diagnoses were likely to be social phobia and specific phobia in children, and generalized anxiety disorder and panic disorder in adults. Mood disorders, consisting mostly of major depressive disorder, also emerged with age, as these were diagnosed in just 3 percent of children but in 20 percent of mature adults.

ADHD was flagged in 37 percent of children, but this diagnosis dropped off in adulthood, affecting 24 percent of adolescents and 16 percent of adults over 18 years of age. Autism diagnoses appeared to peak in adolescence, at 27 percent of 13- to 17-year-olds, although the dataset for this diagnosis was more limited.

Beyond diagnoses
The researchers looked beyond specific diagnoses in a subset of 183 people, between six and 24 years old who had also been measured on their intellectual function and adaptive behaviors, including socialization, communication, and daily living skills. These scores were substantially lower than in the general population, but further analyses found that intellectual function explained only a small portion of the adaptive behavior variance. When age and IQ were controlled for, the researchers found that anxiety disorders were associated with poorer daily living skills.

Teasing apart the influences of IQ and psychiatric contingencies on how a person with 22q11.2 deletions gets on in real life will be challenging. Large-scale longitudinal studies that follow a person throughout life will help. In the meantime, the researchers recommend that school-age children with 22q11.2 deletions be screened and treated for ADHD, whereas adults should be monitored for anxiety and mood disorders, as well as early signs of psychosis. They suggest that early and intensive management of anxiety and depression might help stave off the development of psychosis, or at least reduce the severity of symptoms.—Michele Solis.

Schneider M, Debbané M, Bassett AS, Chow EW, Fung WL, van den Bree M, Owen M, Murphy KC, Niarchou M, Kates WR, Antshel KM, Fremont W, McDonald-McGinn DM, Gur RE, Zackai EH, Vorstman J, Duijff SN, Klaassen PW, Swillen A, Gothelf D, Green T, Weizman A, van Amelsvoort T, Evers L, Boot E, Shashi V, Hooper SR, Bearden CE, Jalbrzikowski M, Armando M, Vicari S, Murphy DG, Ousley O, Campbell LE, Simon TJ, Eliez S, . 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. Am J Psychiatry. 2014 Jun 1; 171(6):627-39. Abstract

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