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

BMC Psychiatry

Study Protocol

Nicholas M. Massa¹  Erica J. Duncan²  Sid L. Imes³  Gabrielle A. Ruban³  David A. Parker³  Joseph F. Cubells⁴  Opal Y. Ousley⁵  Elaine F. Walker⁶  Brett T. Henshey⁷ 

[1] Atlanta Veterans Administration Health Care System, 1670 Clairmont Road, 30033, Decatur, GA, USA;Atlanta Veterans Administration Health Care System, 1670 Clairmont Road, 30033, Decatur, GA, USA;Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Brain Health Center, 12 Executive Park Dr, 30329, Atlanta, GA, USA;Department of Human Genetics, Emory University School of Medicine, Whitehead Biomedical Research Building 615 Michael Street Suite 301, 30322, Atlanta, GA, USA;Department of Human Genetics; Emory Autism Center; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1551 Shoup Court, 30033, Decatur, GA, USA;Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1551 Shoup Court, Decatur, GA, USA;Department of Psychology, Emory University, Psychology and Interdisciplinary Sciences Building Suite 487, 36 Eagle Row, 30322, Atlanta, GA, USA;Emory University, Whitehead Biomedical Research Building 615 Michael Street Suite 301, 30322, Atlanta, GA, USA;

关键词: (up to 10): 22q11.2DS;    DiGeorge syndrome;    Velocardiofacial syndrome;    Deep phenotyping;    Acoustic startle;    EEG;    Mismatch negativity;    Cognition;    Psychosis risk;   

DOI  :  10.1186/s12888-023-04888-5

 received in 2023-03-31, accepted in 2023-05-18,  发布年份 2023

来源: Springer

【 摘 要 】

Background22q11.2 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.MethodsOur 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.DiscussionStudying 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 1