RESUMEN
In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.
Asunto(s)
Trastorno Autístico/genética , Cognición/fisiología , Variaciones en el Número de Copia de ADN/genética , Predisposición Genética a la Enfermedad , Esquizofrenia/genética , Adolescente , Adulto , Anciano , Encéfalo/anomalías , Encéfalo/anatomía & histología , Encéfalo/metabolismo , Estudios de Casos y Controles , Deleción Cromosómica , Cromosomas Humanos/genética , Cromosomas Humanos Par 15/genética , Dislexia/genética , Femenino , Fertilidad/genética , Heterocigoto , Humanos , Islandia , Discapacidades para el Aprendizaje/genética , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Fenotipo , Adulto JovenRESUMEN
BACKGROUND: Dementia is a complex and often debilitating illness, presenting with not only wide-ranging cognitive impairment but also neuropsychiatric challenges, which can have diverse consequences in quality of life for both patient and caregiver. AIM: Studying the validity and reliability of an Icelandic translation of the Neuropsychiatric Inventory with Caregiver Distress (NPI-D). METHODS: NPI-D was administered to 38 primary caregivers of dementia patients. The concurrent validity was explored by statistically comparing the NPI-D to the Behavioural Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the Geriatric Depression Scale (GDS). Regarding caregiver distress, concurrent validity was established between NPI-D, BEHAVE-AD Global Rating and two other caregiver distress scales. RESULTS: Significant correlation was found when total score on the BEHAVE-AD was compared with total score on the NPI-D. All NPI-D subscales achieved significant correlation with the corresponding BEHAVE-AD subscales apart from the 'depression/dysphoria subscale'. This NPI-D subscale correlated however, significantly with the GDS depression scale, a frequent and well validated measure of depressive symptoms in the elderly population. Cronbach's alpha coefficient indicated a high degree of overall internal consistency among the items of the NPI-D. Interestingly, apathy was the most frequent neuropsychiatric disturbance and the only subscale that differed significantly between dementia severity levels. Finally, when studying caregiver distress, the NPI-D showed good concurrent validity with other measures of caregiver burden and distress. CONCLUSIONS: The results demonstrate an acceptable level of validity and reliability; therefore the Icelandic translation of the NPI-D is well suited for identifying neuropsychiatric symptoms in dementia and associated caregiver burden.