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1.
Am J Med Genet B Neuropsychiatr Genet ; 177(8): 765-773, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30444066

RESUMO

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with impairment in multiple domains of cognition and risk for several psychiatric disorders. Musical auditory processing is highly heritable, and is impaired in individuals with schizophrenia and other neurodevelopmental disorders, but has never been studied in 22q11DS, notwithstanding anecdotal evidence of its sparing. We aimed to characterize musical auditory processing in 22q11DS and explore potential relationships with other cognitive domains, musical engagement, and psychiatric disorders. The Distorted Tunes Task and Global Musical Sophistication Index were used to assess pitch discrimination and general musical engagement in 58 individuals with 22q11DS aged 8-29 years. Psychopathology was assessed with sections from the modified Schedule for Affective Disorders and Schizophrenia for School-Age Children and the Structured Interview for Prodromal Syndromes. The Penn computerized neurocognitive battery (CNB) examined four domains of cognition (executive functioning, episodic memory, complex cognition, and social cognition). Significant musical auditory processing impairment and reduced musical engagement were found in individuals with 22q11DS. However, deficits in musical auditory processing were not associated with reduced musical engagement. After covarying for age and sex, episodic memory and overall CNB performance accuracy were significantly related to performance in musical auditory processing. There were no relationships between musical auditory processing and presence of any psychiatric diagnoses. Individuals with 22q11DS experience significant deficits in musical auditory processing and reduced musical engagement. Pitch discrimination is associated with overall cognitive ability, but appears to be largely independent of psychiatric illness.


Assuntos
Percepção Auditiva/genética , Cognição/fisiologia , Síndrome de DiGeorge/fisiopatologia , Síndrome da Deleção 22q11/genética , Síndrome da Deleção 22q11/fisiopatologia , Adolescente , Adulto , Transtornos da Percepção Auditiva/genética , Criança , Síndrome de DiGeorge/genética , Feminino , Humanos , Masculino , Transtornos do Humor/genética , Música/psicologia , Testes Neuropsicológicos , Sintomas Prodrômicos , Psicopatologia/métodos , Transtornos Psicóticos/genética , Esquizofrenia/genética , Comportamento Social , Adulto Jovem
2.
Schizophr Res ; 202: 113-119, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30007867

RESUMO

Olfactory functioning is a promising biomarker for psychosis in 22q11.2 deletion syndrome (22q11DS) but has not been well studied to date. This is a pilot effort to evaluate the potential for tests of olfactory functioning to contribute to risk and resilience prediction in 22q11DS, and is the first study to evaluate relationships among olfactory deficits, cognition and psychosis-spectrum symptoms. Odor identification and discrimination were evaluated in 32 individuals with 22q11DS and 110 healthy comparison subjects (HC). Individuals with 22q11DS also underwent cognitive testing with the Penn Computerized Neurocognitive Battery, which evaluates executive functioning, episodic memory, complex cognition, and social cognition. Positive, negative, disorganized and general psychosis-spectrum symptoms were rated according to the Scale of Prodromal Symptoms. Age-normalized scores were calculated for odor identification and discrimination based on normative data. Both odor identification (p < 0.001, Cohen's d = -2.15, 95% CI [-2.62, -1.68]) and discrimination (p < 0.001, Cohen's d = -1.81, 95% CI [-2.26, -1.35]) were significantly impaired in 22q11DS relative to HC. There were no sex differences in either group. Neither odor identification nor discrimination was correlated with overall cognition or any specific cognitive domain in 22q11DS. Impairment in odor discrimination was correlated with higher negative and overall psychosis-spectrum symptoms. There was no significant effect of catechol-O-methyltransferase Val(158)Met genotype or presence of velopharyngeal insufficiency on olfactory functioning. Olfactory deficits, particularly olfactory discrimination, are robust in 22q11DS and appear to be independent of cognitive deficits. They are also clinically relevant and related to psychosis-spectrum symptoms. Olfactory functioning appears to be a promising biomarker for psychosis in 22q11DS.


Assuntos
Síndrome da Deleção 22q11/diagnóstico , Disfunção Cognitiva/diagnóstico , Transtornos do Olfato/diagnóstico , Transtornos Psicóticos/diagnóstico , Síndrome da Deleção 22q11/complicações , Síndrome da Deleção 22q11/fisiopatologia , Adolescente , Adulto , Biomarcadores , Criança , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Masculino , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Projetos Piloto , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/fisiopatologia , Adulto Jovem
3.
Biol Psychiatry ; 82(1): 17-25, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27832840

RESUMO

BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11DS) is a promising model for studying psychosis risk. Direct comparisons of psychosis features between 22q11DS and nondeleted (ND) individuals are limited by inconsistency and small samples. In the largest study to date, we compare 22q11DS to ND in comorbidities, functioning, cognition, and psychosis features across the full range of overall severity. METHODS: ND youths (n = 150) ages 9 to 24 years were matched to 22q11DS individuals (n = 150) on age and sex, stratifying for presence of psychosis spectrum disorder. Individuals were evaluated for psychosis using the Structured Interview for Prodromal Syndromes, and for attention-deficit/hyperactivity, substance-related, and mood disorders. Differential item functioning analysis addressed whether 22q11DS differs from ND in the probability of clinically significant ratings while holding constant the overall level of psychosis. RESULTS: Onset of psychosis proneness was similar among 22q11DS (mean: 11.0 years) and ND (mean: 12.1 years) individuals. Accounting for higher overall psychosis symptoms, 22q11DS participants were still more likely to manifest impaired stress tolerance, avolition, and ideational richness; ND individuals were more likely to exhibit unusual thoughts, persecutory ideas, and bizarre thinking. Cognition was impaired in 22q11DS, but it did not correlate with symptoms except ideational richness. Comorbid anxiety disorders were more likely in psychosis spectrum 22q11DS; substance-related disorders were more likely in ND. Global assessment of function was similar in 22q11DS and ND individuals, except among those with low total Structured Interview for Prodromal Syndromes scores. CONCLUSIONS: Individuals with 22q11DS share overarching similarities with ND individuals in psychosis symptoms and age of onset for psychosis proneness; this continues to support the 22q11DS model as a valuable window into mechanisms contributing to psychosis.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Síndrome de DiGeorge/epidemiologia , Síndrome de DiGeorge/psicologia , Transtornos do Humor/epidemiologia , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Cognição , Comorbidade , Feminino , Humanos , Masculino , Pennsylvania/epidemiologia , Fatores de Tempo , Adulto Jovem
4.
Brain Cogn ; 106: 33-41, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27200494

RESUMO

Increasingly, the effects of copy number variation (CNV) in the genome on brain function and behaviors are recognized as means to elucidate pathophysiology of psychiatric disorders. Such studies require large samples and we characterized the neurocognitive profile of two cohorts of individuals with 22q11.2 deletion syndrome (22q11DS), the most common CNV associated with schizophrenia, in an effort to harmonize phenotyping in multi-site global collaborations. The Penn Computerized Neurocognitive Battery (PCNB) was administered to individuals with 22q11DS in Philadelphia (PHL; n=155, aged 12-40) and Tel Aviv (TLV; n=59, aged 12-36). We examined effect sizes of performance differences between the cohorts and confirmed the factor structure of PCNB performance efficiency in the combined sample based on data from a large comparison community sample. The cohorts performed comparably with notable deficits in executive function, episodic memory and social cognition domains that were previously associated with abnormal neuroimaging findings in 22q11DS. In mixed model analysis, while there was a main effect for site for accuracy (number of correct response) and speed (time to correct response) independently, there were no main site effects for standardized efficiency (average of accuracy and speed). The fit of a structural model was excellent indicating that PCNB tests were related to the targeted cognitive domains. Thus, our results provide preliminary support for the use of the PCNB as an efficient tool for neurocognitive assessment in international 22q11DS collaborations.


Assuntos
Síndrome de DiGeorge/fisiopatologia , Função Executiva/fisiologia , Memória Episódica , Testes Neuropsicológicos , Percepção Social , Adolescente , Adulto , Criança , Estudos de Coortes , Comparação Transcultural , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/normas , Esquizofrenia/genética , Estados Unidos , Adulto Jovem
5.
J Clin Psychiatry ; 76(10): e1262-70, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26528648

RESUMO

OBJECTIVE: Presence of psychiatric comorbidity is associated with poor functioning and is an important consideration in treatment. Many individuals with 22q11.2 deletion syndrome (22q11DS) develop comorbid psychiatric disorders, yet its pattern and impact on functioning have not been formally investigated. In this cross-sectional study, we examined the relationship between comorbid psychopathology and neurocognitive deficits and their association with global functioning. We hypothesized that higher psychiatric burden and psychosis-spectrum features would be associated with reduced functioning and increased neurocognitive deficits. METHOD: The cohort included 171 individuals with 22q11DS and mean (SD) age of 17.4 (8.1) years, recruited from a tertiary children's hospital and nationally through social media between September 2010 and December 2013. Psychiatric diagnoses and functioning were assessed using semistructured interviews and the Global Assessment of Functioning (GAF) scale, respectively. On the basis of psychopathology and number of comorbid diagnoses, participants were assigned to unaffected (n = 32), nonpsychosis spectrum (n = 24), nonpsychosis spectrum-plus (n = 15), psychosis spectrum (n = 29), and psychosis spectrum-plus (n = 71) groups. Executive function, episodic memory, complex cognition, social cognition, and praxis speed were assessed using a computerized neurocognitive battery (CNB). Cognitive profile and GAF scores were compared among the groups, and the association of GAF with cognitive performance and psychopathology was examined. RESULTS: We observed high rates of comorbid psychiatric disorders. Approximately 50% of the participants had ≥ 2 diagnoses. Psychosis spectrum disorders were most frequently comorbid with other disorders. GAF score was progressively worse with increased psychiatric burden. Mean (SD) GAF score for the unaffected group (81.1 [8.9]) was significantly different from those of nonpsychosis spectrum (68.6 [12.1]), nonpsychosis spectrum-plus (63.4 [8.8]), psychosis spectrum (58.7 [13.1]), or psychosis spectrum-plus (55.5 [13.3]) (P < .05) groups. All groups performed poorly and were comparable to each other on the CNB (P = .273). Notably, verbal memory (P = .003), spatial processing (P = .001), and parent education level (P < .001) were significantly associated with GAF. CONCLUSIONS: Individuals with 22q11DS have high rates of comorbid psychiatric disorders and diffuse cognitive deficits regardless of psychiatric burden. Those with psychotic spectrum disorders and comorbid psychiatric disorders are at an increased risk for poor overall functioning.


Assuntos
Transtornos Cognitivos/epidemiologia , Síndrome de DiGeorge/epidemiologia , Transtornos Mentais/epidemiologia , Adolescente , Adulto , Criança , Transtornos Cognitivos/genética , Comorbidade , Estudos Transversais , Síndrome de DiGeorge/psicologia , Feminino , Humanos , Entrevista Psicológica , Masculino , Transtornos Mentais/genética , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Psicopatologia , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/genética , Adulto Jovem
6.
J Am Acad Child Adolesc Psychiatry ; 53(9): 991-1000.e2, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25151422

RESUMO

OBJECTIVE: Chromosome 22q11.2 deletion syndrome (22q11DS) confers 25% risk for psychosis and is an invaluable window for understanding the neurobiological substrate of psychosis risk. The Structured Interview for Prodromal Syndromes (SIPS) is well validated in nondeleted populations for detecting clinical risk but has only recently been applied to 22q11DS. We assessed the largest 22q11DS cohort to date and report on SIPS implementation and symptoms elicited. METHOD: The SIPS, including its 19 subscales, was administered to 157 individuals with 22q11DS aged 8 to 25 years. Youth and caregiver interviews were conducted and rated separately, then compared for agreement. Implementation of the SIPS in 22q11DS was challenging because of the prevalence of developmental delay and comorbid conditions. However, by explaining questions and eliciting examples, we were able to help youths and caregivers understand and respond appropriately. Consensus ratings were formulated and analyzed with itemwise and factor analysis. RESULTS: Subthreshold symptoms were common, with 85% of individuals endorsing 1 or more. The most commonly rated items were ideational richness (47%) and trouble with focus and attention (44%). Factor analysis revealed a 3-factor solution with positive, negative, and disorganized components. Youth-caregiver comparisons suggested that youths report greater symptoms of perceptual abnormalities, suspiciousness, trouble with emotional expression, and bizarre thinking. Caregivers reported more impaired tolerance to normal stress, poor hygiene, and inattention. CONCLUSION: The SIPS was adapted for 22q11DS through comprehensive and semi-structured administration methods, yielding a high prevalence of subthreshold psychotic symptoms. The significance and predictive validity of these symptoms require future longitudinal analysis.


Assuntos
Síndrome da Deleção 22q11/fisiopatologia , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Síndrome da Deleção 22q11/complicações , Adolescente , Adulto , Feminino , Humanos , Masculino , Sintomas Prodrômicos , Transtornos Psicóticos/etiologia , Adulto Jovem
7.
Am J Med Genet B Neuropsychiatr Genet ; 165B(2): 137-47, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24265253

RESUMO

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.


Assuntos
Transtornos de Ansiedade/genética , Síndrome de DiGeorge/genética , Predisposição Genética para Doença , Transtornos Psicóticos/genética , Adolescente , Criança , Cromossomos Humanos Par 22 , Cognição/fisiologia , Síndrome de DiGeorge/etiologia , Feminino , Testes Genéticos/métodos , Humanos , Masculino
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