Computerized neurocognitive profile in young people with 22q11.2 deletion syndrome compared to youths with schizophrenia and At-Risk for psychosis

Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.42). 01/2012; 159B(1):87-93. DOI: 10.1002/ajmg.b.32005
Source: PubMed


Adults with 22q11.2 Deletion syndrome (22q11DS) have increased prevalence of schizophrenia features. Our goal is to compare the neurocognitive profile in 22q11DS, schizophrenia and individuals at risk for schizophrenia. Twenty-one 22q11DS patients (8-32 years, mean 14.9 years, 15M, 6F) were matched to four comparison groups on age: low risk (n = 21), first-degree family members of schizophrenia patients (genetic risk, n = 20), individuals exhibiting putatively prodromal symptoms (clinical risk, n = 19), and patients with schizophrenia (n = 21). All participants received semi-structured interviews [Diagnostic Interview for Genetic Studies (DIGS) and the Structured Interview for Prodromal Syndromes (SIPS)], and a computerized neurocognitive battery (CNB) measuring the following domains: Abstraction and Mental Flexibility, Attention, Working Memory, Verbal Memory, Face Memory, Spatial Memory, Language, Spatial Processing, Sensorimotor Dexterity, and Emotion Processing. Sixty percent of 22q11DS participants met SIPS criteria for prodromal symptoms and one participant met criteria for paranoid schizophrenia. Thirty-eight percent met criteria for Depressive Disorders. All 22q11DS participants successfully completed the CNB. 22q11DS participants were significantly less accurate in nearly all domains, but had similar speed of response compared to the other groups. Their profile resembled that of the psychosis groups in accuracy and speed, except for more pronounced deficits in accuracy for face memory and emotion processing. Subthreshold psychotic symptoms are present in a high proportion of 22q11DS participants. Deficits shown in the CNB are more pronounced for accuracy than speed relative to the psychosis groups with similar profiles. Similar deficits have been described in the 22q11DS population using non-computerized measures, which require increased testing time.

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Available from: Donna M McDonald Mcginn,
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    • "It is characterized by a host of congenital abnormalities including congenital heart disease (CHD), palatal defects, immune deficiencies and thymic hypoplasia [Ryan et al., 1997; Botto et al., 2003; McDonald-McGinn and Sullivan, 2011]. Most affected individuals have deficits in language, motor, visual-spatial processing, executive function, memory, and social cognition [Golding-Kushner et al., 1984; Gerdes et al., 1999; Bearden et al., 2001; Kiley-Brabeck and Sobin, 2006; De Smedt et al., 2007; Ousley et al., 2007; Van Aken et al., 2007; Goldenberg et al., 2012; Howley et al., 2012]. High prevalence of psychiatric disorders has been associated with the syndrome. "
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    ABSTRACT: Children with 22q11.2 deletion syndrome (22q11DS) present with congenital heart disease (CHD) and high prevalence of psychiatric disorders and neurocognitive deficits. Although CHD has been implicated in neurodevelopment, its role in the neuropsychiatric outcome in 22q11DS is poorly understood. We investigated whether CHD contributes to the high prevalence of psychiatric disorders and neurocognitive impairments in 22q11DS. Fifty-four children ages 8-14 years with 22q11DS and 16 age-matched non-deleted children with CHD participated. They were assessed using semi-structured interviews and a Computerized Neurocognitive Battery. CHD status was assessed using available medical records. Prevalence of psychiatric disorders and cognitive profiles were compared among the groups. There were no significant differences between the prevalence of psychiatric disorders in the 22q11DS with and without CHD. In 22q11DS with CHD, the prevalence rates were 41% anxiety disorders, 37% ADHD and 71% psychosis spectrum. In 22q11DS without CHD, the rates were 33% anxiety disorders, 41% ADHD and 64% psychosis spectrum. In comparison, the non-deleted CHD group had lower rates of psychopathology (25% anxiety disorders, 6% ADHD, and 13% psychosis spectrum). Similarly, the 22q11DS groups, regardless of CHD status, had significantly greater neurocognitive deficits across multiple domains, compared to the CHD-only group. We conclude that CHD in this sample of children with 22q11.2DS does not have a major impact on the prevalence of psychiatric disorders and is not associated with increased neurocognitive deficits. These findings suggest that the 22q11.2 deletion status itself may confer significant neuropsychiatric vulnerability in this population. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 03/2014; 165(2). DOI:10.1002/ajmg.b.32215 · 3.42 Impact Factor
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    • "Applying a systematic procedure for selecting behavioral measures for functional imaging and adapting them to the study of individual differences (R. C. Gur et al., 1992), we validated a computerized battery that profiles major neurobehavioral domains: executive control, episodic memory, reasoning, social cognition, and processing speed (R. C. Gur, Ragland, Moberg, Turner, et al., 2001; R. C. Gur et al., 2010). This CNB has been applied in normative samples (R. C. Gur, Ragland, Moberg, Turner, et al., 2001; Irani et al., 2012; Silver, Goodman, Gur, Gur, & Bilker, 2011), large-scale genetic studies (Almasy et al., 2008; Calkins et al., 2010; R. E. Gur et al., 2007), including children (R. C. Gur et al., 2012), and neuropsychiatric populations (Goldenberg et al., 2012; R. C. Gur, Ragland, Moberg, Bilker, et al., 2001; Silver, Feldman, Bilker, & Gur, 2003). Here, we describe an adaptation of the CNB to fMRI (fCNB), designed to link brain activation to concurrent performance. "
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    ABSTRACT: Objective: The advent of functional MRI (fMRI) enables the identification of brain regions recruited for specific behavioral tasks. Most fMRI studies focus on group effects in single tasks, which limits applicability where assessment of individual differences and multiple brain systems is needed. Method: We demonstrate the feasibility of concurrently measuring fMRI activation patterns and performance on a computerized neurocognitive battery (CNB) in 212 healthy individuals at 2 sites. Cross-validated sparse regression of regional brain amplitude and extent of activation were used to predict concurrent performance on 6 neurocognitive tasks: abstraction/mental flexibility, attention, emotion processing, and verbal, face, and spatial memory. Results: Brain activation was task responsive and domain specific, as reported in previous single-task studies. Prediction of performance was robust for most tasks, particularly for abstraction/mental flexibility and visuospatial memory. Conclusions: The feasibility of administering a comprehensive neuropsychological battery in the scanner was established, and task-specific brain activation patterns improved prediction beyond demographic information. This benchmark index of performance-associated brain activation can be applied to link brain activation with neurocognitive performance during standardized testing. This first step in standardizing a neurocognitive battery for use in fMRI may enable quantitative assessment of patients with brain disorders across multiple cognitive domains. Such data may facilitate identification of neural dysfunction associated with poor performance, allow for identification of individuals at risk for brain disorders, and help guide early intervention and rehabilitation of neurocognitive deficits.
    Neuropsychology 12/2013; 28(2). DOI:10.1037/neu0000011 · 3.27 Impact Factor
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    ABSTRACT: Copy number variation (CNV) of human chromosome 22q11.2 is associated with an elevated rate of autism spectrum disorder (ASD) and represents one of syndromic ASDs with rare genetic variants. However, the precise genetic basis of this association remains unclear due to its relatively large hemizygous and duplication region, including more than 30 genes. Previous studies using genetic mouse models suggested that although not all 22q11.2 genes contribute to ASD symptomatology, more than one 22q11.2 genes have distinct phenotypic targets for ASD symptoms. Our data show that deficiency of the two 22q11.2 genesTbx1 and Sept5 causes distinct phenotypic sets of ASD symptoms.
    Autism Open Access 09/2012; Suppl 1:001. DOI:10.4172/2165-7890.S1-001
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