Deep psychophysiological phenotyping of adolescents and adults with 22q11.2 deletion syndrome: a multilevel approach to defining core disease processes

• Type of Material: Article
• Authors: David A Parker, Emory University; Joseph Cubells, Emory University; Sid L Imes, Emory University; Gabrielle A Ruban, Emory University; Brett T Henshey, Emory University; Nicholas M Massa, Atlanta Veterans Affairs Health Care System; Elaine Walker, Emory University; Erica Duncan, Emory University; Opal Ousley, Emory University
• Language: English
• Date: 2023-12-01
• Publisher: BioMed Central Ltd
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12888-023-04888-5
• Title of Journal or Parent Work: BMC Psychiatry
• Volume: 23
• Issue: 1
• Start Page: 425
• End Page: 425
• Grant/Funding Information: NIH/NIMH R01MH117315 to JFC and ED, NIH/NCATS UL1TR002378 TL1TR002382 to DP; Department of Psychiatry and Behavioral Sciences within the Emory University School of Medicine general support funds to OO.
• Keywords: DiGeorge Syndrome; EEG; Young Adult; Humans; Chromosome Deletion; Acoustic startle; DiGeorge syndrome; Autistic Disorder; Mismatch negativity; Deep phenotyping; Psychotic Disorders; Cognition; Adolescent; Adult; Child; (up to 10): 22q11.2DS; Child Development Disorders, Pervasive; Middle Aged; Psychosis risk; Longitudinal Studies; Velocardiofacial syndrome
• Research Categories: Health Sciences, Mental Health; Psychology, General

Abstract

Background: 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal interstitial-deletion disorder, occurring in approximately 1 in 2000 to 6000 live births. Affected individuals exhibit variable clinical phenotypes that can include velopharyngeal anomalies, heart defects, T-cell-related immune deficits, dysmorphic facial features, neurodevelopmental disorders, including autism, early cognitive decline, schizophrenia, and other psychiatric disorders. Developing comprehensive treatments for 22q11.2DS requires an understanding of both the psychophysiological and neural mechanisms driving clinical outcomes. Our project probes the core psychophysiological abnormalities of 22q11.2DS in parallel with molecular studies of stem cell-derived neurons to unravel the basic mechanisms and pathophysiology of 22q11.2-related psychiatric disorders, with a primary focus on psychotic disorders. Our study is guided by the central hypothesis that abnormal neural processing associates with psychophysiological processing and underlies clinical diagnosis and symptomatology. Here, we present the scientific background and justification for our study, sharing details of our study design and human data collection protocol. Methods: Our study is recruiting individuals with 22q11.2DS and healthy comparison subjects between the ages of 16 and 60 years. We are employing an extensive psychophysiological assessment battery (e.g., EEG, evoked potential measures, and acoustic startle) to assess fundamental sensory detection, attention, and reactivity. To complement these unbiased measures of cognitive processing, we will develop stem-cell derived neurons and examine neuronal phenotypes relevant to neurotransmission. Clinical characterization of our 22q11.2DS and control participants relies on diagnostic and research domain criteria assessments, including standard Axis-I diagnostic and neurocognitive measures, following from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and the North American Prodrome Longitudinal Study (NAPLS) batteries. We are also collecting measures of autism spectrum (ASD) and attention deficit/hyperactivity disorder (ADHD)-related symptoms. Discussion: Studying 22q11.2DS in adolescence and adulthood via deep phenotyping across multiple clinical and biological domains may significantly increase our knowledge of its core disease processes. Our manuscript describes our ongoing study’s protocol in detail. These paradigms could be adapted by clinical researchers studying 22q11.2DS, other CNV/single gene disorders, or idiopathic psychiatric syndromes, as well as by basic researchers who plan to incorporate biobehavioral outcome measures into their studies of 22q11.2DS.