Jolin EM, Weller RA, Weller EB. Occurrence of affective disorders compared to other psychiatric disorders in children and adolescents with 22q11.2 deletion syndrome. J Affect Disord 136: 222-228

Department of Sociomedical Sciences, Boston University School of Medicine, Boston, MA, United States.
Journal of Affective Disorders (Impact Factor: 3.38). 11/2011; 136(3):222-8. DOI: 10.1016/j.jad.2010.11.025
Source: PubMed


22q11.2 deletion syndrome (22qDS) is a common genetic disorder with highly variable clinical manifestations that may include depression, bipolar disorder and schizophrenia. Studies of psychiatric disorders in youth with 22qDS often had methodological limitations. This study reviewed clinical studies with the currently best available methodology to determine the occurrence of affective disorders compared to other psychiatric disorders in youth with 22qDS.
A PubMed search was performed to identify psychiatric studies published from 2000 through 2009 of children and adolescents with genetically confirmed 22qDS who underwent systematic psychiatric assessments. Studies that met defined inclusion/exclusion criteria were selected for further analysis.
Seven studies with a total of 323 children and adolescents with 22qDS (mean age=10.8 years) met the defined inclusion/exclusion criteria. Depressive disorders, but not bipolar spectrum disorders, were increased compared to community-based rates in youth without 22qDS. Anxiety disorders and attention-deficit/hyperactivity disorder were the most frequent disorders. Although psychotic-like phenomena and schizotypical traits were reported, only two adolescents (<1%) had a psychotic disorder.
Unknown selection and assessment factors may have impacted on occurrence rates.
The elevated occurrence of depressive, anxiety, and attention disorders in children with 22qDS, compared to community-based rates in children without 22qDS, suggest that psychiatric screening is needed. Longitudinal study is needed to determine if these childhood psychiatric disorders will resolve, continue into adulthood, or develop into more serious psychopathology.

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    • "Psychiatric symptoms are common. Children and adolescents with velo–cardio–facial syndrome are at increased risk for depression, anxiety, and attention-deficit/hyperactivity disorders.94,95 Obsessive–compulsive behavior and autistic features are also not uncommon. "
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    ABSTRACT: Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs) and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a "risk" allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian syndromes, psychiatric symptoms are prevalent. Although these conditions do not fit the classic description of any specific psychiatric disorder, they often show nonspecific psychiatric symptoms that cross diagnostic boundaries, including intellectual disability, behavioral abnormalities, mood disorders, anxiety disorders, attention deficit, impulse control deficit, and psychosis. Although testing for chromosomal disorders and monogenic Mendelian disorders is well established, testing for common variants is still controversial. The standard concept of genetic testing includes at least three broad criteria that need to be fulfilled before new genetic tests should be introduced: analytical validity, clinical validity, and clinical utility. These criteria are currently not fulfilled for common genomic variants in psychiatric disorders. Further work is clearly needed before genetic testing for common variants in psychiatric disorders should be established.
    The Application of Clinical Genetics 02/2014; 7:33-42. DOI:10.2147/TACG.S39297
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    • "The most commonly reported neuropsychiatric disorders during childhood are attention deficit disorder (present in 30%–40% of individuals with 22q11DS)34 and autism spectrum disorders (10%–30%),39 but anxiety disorders, especially simple phobias and separation anxiety, (present in 30%–40%) and mood disorders including major depression and bipolar disorder (present in 20%–30%)33,39 are also common and increase in prevalence during adolescence.124 Obsessive compulsive disorder has also been reported.125 "
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    ABSTRACT: The 22q11.2 deletion syndrome (22q11DS) is caused by an autosomal dominant microdeletion of chromosome 22 at the long arm (q) 11.2 band. The 22q11DS is among the most clinically variable syndromes, with more than 180 features related with the deletion, and is associated with an increased risk of psychiatric disorders, accounting for up to 1%-2% of schizophrenia cases. In recent years, several genes located on chromosome 22q11 have been linked to schizophrenia, including those encoding catechol-O-methyltransferase and proline dehydrogenase, and the interaction between these and other candidate genes in the deleted region is an important area of research. It has been suggested that haploinsufficiency of some genes within the 22q11.2 region may contribute to the characteristic psychiatric phenotype and cognitive functioning of schizophrenia. Moreover, an extensive literature on neuroimaging shows reductions of the volumes of both gray and white matter, and these findings suggest that this reduction may be predictive of increased risk of prodromal psychotic symptoms in 22q11DS patients. Experimental and standardized cognitive assessments alongside neuroimaging may be important to identify one or more endophenotypes of schizophrenia, as well as a predictive prodrome that can be preventively treated during childhood and adolescence. In this review, we summarize recent data about the 22q11DS, in particular those addressing the neuropsychiatric and cognitive phenotypes associated with the deletion, underlining the recent advances in the studies about the genetic architecture of the syndrome.
    Neuropsychiatric Disease and Treatment 12/2013; 9:1873-1884. DOI:10.2147/NDT.S52188 · 1.74 Impact Factor
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    • "Therefore, none of these disorders, if diagnosed, fulfills the criteria (Feinstein et al. 2002) set forth for a behavioral phenotype that is specifically associated with a syndrome. By late adolescence and early adulthood, up to one-third of patients with 22q11DS develop psychotic disorders resembling above all schizophrenia and schizoaffective disorder (Murphy et al. 1999, Bassett et al. 2003, Gothelf et al. 2007, Jolin 2012). Therefore, 22q11DS is of considerable interest to research concerned with the genetic and epigenetic mechanisms involved in the development of schizophrenic disorder. "
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    ABSTRACT: Objective: 22q11.2 deletion syndrome (22q11DS) is a genetic syndrome associated with a microdeletion of the chromosome 22 band q11 with an estimated prevalence of between 1:2,500 and 1:4,000 live births. Studies of school-age children have shown that individuals with 22q11DS have very high rates of psychiatric morbidity and abnormal behaviors. By late adolescence and early adulthood, up to one-third of patients with 22q11DS develop psychotic disorders resembling above all schizophrenia and schizoaffective disorder. Therefore, 22q11DS is of considerable interest to research concerned with the genetic and epigenetic mechanisms involved in the development of schizophrenic disorder. Method: A comprehensive literature review based on PubMed/MEDLINE, Cochrane Library, Cinhal and PsycInfo was undertaken. Results: Schizophrenic disorder associated with 22q11DS largely resembles that found in the general population as regards the core signs and symptoms, treatment response, neurocognitive profile and MRI brain anomalies. Conclusions: Individuals with 22q11DS are an easy identifiable high-risk group for schizophrenia whose transition rate in early adulthood may be as high as 30%, regardless of environmental factors. This syndrome is thus of considerable interest to researchers and clinicians involved in the early intervention/prevention of schizophrenia. Declaration of interest: none Marco Armando(a, b, c); Maria Pontillo (a); Franco De Crescenzo (a); Cinzia Correale (a); Enrica De Simoni (d); Francesco Papaleo (e, f); Riccardo Saba (b); Stefano Vicari (a).
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