Lower Prepulse Inhibition in Children With the 22q11 Deletion Syndrome

Abstract

Objective-The 22q11 deletion syndrome is associated with a range of possible physical anomalies, probable ongoing learning disabilities, and a specific constellation of neuropsychological deficits, including impairments in selective and executive visual attention, working memory, and sensorimotor functioning. It has been estimated that 25% of the children with 22q11 deletion syndrome go on to develop schizophrenia in late adolescence or adulthood. This is of urgent concern. Specification of early brain network vulnerabilities may provide a basis for early intervention while indicating critical links between genes and severe psychiatric illness. Neuropsychological studies of children with 22q11 deletion syndrome have implicated an array of potentially aberrant brain pathways. This study was conducted to determine whether preattentive processing ("sensorimotor gating") deficits are present in this population.Method-The authors administered a test of prepulse inhibition to 25 children with 22q11 deletion syndrome and their 23 sibling comparison subjects, ages 6-13. It was predicted that the children with 22q11 deletion syndrome would have lower prepulse inhibition than the comparison subjects.Results-Prepulse inhibition in the children with 22q11 deletion syndrome (26.06%) was significantly less than that of the sibling comparison subjects (46.41%). Secondary analyses suggested that this decrement did not reflect developmental delay, and lower prepulse inhibition was associated with particular subsyndromal symptoms in some children.Conclusions-Sensorimotor gating is lower in children with 22q11 deletion syndrome. These findings may indicate specific brain circuits that are anomalous in 22q11 deletion syndrome.The 22q11 deletion syndrome results from a meiotic deletion of genetic material at the q11.2 site on chromosome 22. It occurs in 1 of every 6,000 births (1) and in over 90% of the cases is de novo (2). Associated congenital anomalies occur in some but not all children and may include heart defects, immunologic deficits, craniofacial dysmorphologies, velopharyngeal defects such as overt or submucous cleft palate, or inflammation-related pain syndromes (3). Before the identification of a single underlying deletion, the different clinical labels described a child's primary physical anomaly and included "conotruncal anomaly face syndrome" (heart defect with facial dysmorphologies), "velocardiofacial syndrome" (velopharyngeal, heart, and facial anomalies), and "DiGeorge syndrome" (immunologic insufficiency).Broadly speaking, the academic and neuropsychological profile of children with 22q11 deletion syndrome is more consistent than their physical phenotype. Gross motor, fine motor, and expressive language delays have been identified in the early years (4) and are followed by learning disabilities and academic failures, attention impairment, and behavioral anomalies in an estimated 90%-100% of the school-age children with this syndrome (5,6 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manu...

Associations between prepulse inhibition and executive visual attention in children with the 22q11 deletion syndrome

“…29 The PRODH gene encodes proline dehydrogenase, which is key in the production of glutamate; glutamate in turn directly influences GABA production and release. The COMT gene encodes catechol-Omethyltransferase, which catabolizes excess brain dopamine.…”

“…The comparability of this method to the electromyographic (EMG) method was previously demonstrated and discussed. 29,37 Auditory stimuli for the PPI paradigm were presented binaurally through Sony MDR-V6 headphones nested over the LED headband. A background white noise of 50 db (A scale) was present before, in between, and after all trial stimuli presentations.…”

“…19,28 Recently, as compared with 23 sibling controls, PPI among 25 children with 22q11DS was 20% less; secondary analyses suggested that this decrement did not reflect developmental delay. 29 The Attention Network Test (ANT) assesses the efficiency of three relatively segregated brain networks responsible for fundamental aspects of visual attention, including Alerting, Orienting, and Executive functions. ANT index scores represent response time differences in cued and uncued conditions and indicate the amount of cue benefit derived.…”

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

“…One indication supporting the former possibility is the recent report that PPI is normal in effectively treated, non-manic patients with childhood bipolar disorder (Rich et al, 2005). In additional studies prompted in part by suggested genetic contributions to schizophrenia or related disorders, deficits in PPI have also been identified in children with 22q deletion syndrome (Sobin et al, 2005), young persons with Fragile X syndrome (Frankland et al, 2004), and adults with Asperger's syndrome (McAlonan et al, 2002), seizure disorder (Pouretemad et al, 1998), or Lewy body dementia (Perriol et al, 2005).…”

Animal Models of Deficient Sensorimotor Gating in Schizophrenia: Are They Still Relevant?

“…Compared with matched controls, PPI is deficient in patients with schizophrenia (e.g., Braff et al 1978;Swerdlow et al 2006), Huntington's disease Valls-Sole et al 2004), obsessive-compulsive disorder (OCD) Hoenig et al 2005;Ahmari et al 2012), nocturnal enuresis (Ornitz et al 1992), Asperger's syndrome (McAlonan et al 2002), 22q11 syndrome (Sobin et al 2005), Kleinfelter syndrome (Van Rijn et al 2011), fragile X syndrome (Frankland et al 2004), blepharospasm (Gomez-Wong et al 1998, and Tourette syndrome (Castellanos et al 1996;Swerdlow et al 2001b).…”