RESUMEN
BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS subjects' acoustic startle responses (ASRs), which putatively index psychosis risk. Latency of the ASR is a presumptive marker of neural processing speed and is prolonged (slower) in schizophrenia. ASR measures correlate with increased psychosis risk, depend on glutamate and dopamine receptor signaling, and could serve as translational biomarkers in interventions for groups at high psychosis risk. METHODS: Startle magnitude, latency, and prepulse inhibition were assessed with a standard acoustic startle paradigm in 31 individuals with 22q11.2DS and 32 healthy comparison (HC) subjects. Surface electrodes placed on participants' orbicularis oculi recorded the electromyographic signal in ASR eyeblinks. Individuals without measurable startle blinks in the initial habituation block were classified as non-startlers. RESULTS: Across the startle session, the ASR magnitude was significantly lower in 22q11DS subjects than HCs because a significantly higher proportion of 22q11DS subjects were non-startlers. Latency of the ASR to pulse-alone stimuli was significantly slower in 22q11DS than HC subjects. Due to the overall lower 22q11DS startle response frequency and magnitudes prepulse inhibition could not be analyzed. CONCLUSIONS: Reduced magnitude and slow latency of 22q11DS subjects' responses suggest reduced central nervous system and neuronal responsiveness. These findings are consistent with significant cognitive impairments observed in 22q11DS subjects. Further research is needed to untangle the connections among basic neurotransmission dysfunction, psychophysiological responsiveness, and cognitive impairment.
Asunto(s)
Parpadeo , Síndrome de DiGeorge , Inhibición Prepulso , Reflejo de Sobresalto , Humanos , Masculino , Femenino , Reflejo de Sobresalto/fisiología , Adulto , Adolescente , Adulto Joven , Síndrome de DiGeorge/fisiopatología , Inhibición Prepulso/fisiología , Parpadeo/fisiología , Tiempo de Reacción/fisiología , Electromiografía , Estimulación AcústicaRESUMEN
The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. We report the first in-depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). We also explore correlations between psychotic symptoms and posterior fossa abnormalities. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms; ratings demonstrated select sex differences but no domain-wise correlations with IQ. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in psychosis-risk.
Asunto(s)
Síndrome de DiGeorge , Trastornos Psicóticos , Esquizofrenia , Humanos , Femenino , Masculino , Esquizofrenia/complicaciones , Esquizofrenia/genética , Variaciones en el Número de Copia de ADN/genética , Trastornos Psicóticos/complicaciones , Trastornos Psicóticos/genética , Trastornos Psicóticos/diagnósticoRESUMEN
LAY ABSTRACT: Insomnia, trouble falling asleep or staying asleep, is common in autistic children. In a previous report, we described the results of focus groups with parents of autistic children toward the development of the Pediatric Autism Insomnia Rating Scale. In this article, we report on the steps taken to complete the Pediatric Autism Insomnia Rating Scale. With help from the Simons Foundation registry, we collected information from parents on 1185 children with autism spectrum disorder to test the new measure. These results were evaluated using standard statistical methods such as factor analysis. To confirm the validity of the new measure, we enrolled a separate sample of 134 autistic children for a detailed assessment by video conference. This step showed that the Pediatric Autism Insomnia Rating Scale is clearly measuring symptoms of insomnia in children with autism spectrum disorder and not related problems such as hyperactivity, repetitive behavior, or anxiety. We also showed that the total score on the Pediatric Autism Insomnia Rating Scale is stable when repeated over a brief period of time. This is important because a measure that is not stable over a brief period of time would not be suitable as an outcome measure. In summary, the Pediatric Autism Insomnia Rating Scale is a brief and valid measure of insomnia in children with autism spectrum disorder that provides reliable scores.