학술논문
Morphometric network-based abnormalities correlate with psychiatric comorbidities and gene expression in PCDH19-related developmental and epileptic encephalopathy
Document Type
article
Author
Matteo Lenge; Simona Balestrini; Antonio Napolitano; Davide Mei; Valerio Conti; Giulia Baldassarri; Marina Trivisano; Simona Pellacani; Letizia Macconi; Daniela Longo; Maria Camilla Rossi Espagnet; Simona Cappelletti; PCDH19 Clinical Study Group; Ludovico D’Incerti; Carmen Barba; Nicola Specchio; Renzo Guerrini
Source
Translational Psychiatry, Vol 14, Iss 1, Pp 1-13 (2024)
Subject
Language
English
ISSN
2158-3188
Abstract
Abstract Protocadherin-19 (PCDH19) developmental and epileptic encephalopathy causes an early-onset epilepsy syndrome with limbic seizures, typically occurring in clusters and variably associated with intellectual disability and a range of psychiatric disorders including hyperactive, obsessive-compulsive and autistic features. Previous quantitative neuroimaging studies revealed abnormal cortical areas in the limbic formation (parahippocampal and fusiform gyri) and underlying white-matter fibers. In this study, we adopted morphometric, network-based and multivariate statistical methods to examine the cortex and substructure of the hippocampus and amygdala in a cohort of 20 PCDH19-mutated patients and evaluated the relation between structural patterns and clinical variables at individual level. We also correlated morphometric alterations with known patterns of PCDH19 expression levels. We found patients to exhibit high-significant reductions of cortical surface area at a whole-brain level (left/right p value = 0.045/0.084), and particularly in the regions of the limbic network (left/right parahippocampal gyri p value = 0.230/0.016; left/right entorhinal gyri p value = 0.002/0.327), and bilateral atrophy of several subunits of the amygdala and hippocampus, particularly in the CA regions (head of the left CA3 p value = 0.002; body of the right CA3 p value = 0.004), and differences in the shape of hippocampal structures. More severe psychiatric comorbidities correlated with more significant altered patterns, with the entorhinal gyrus (p value = 0.013) and body of hippocampus (p value = 0.048) being more severely affected. Morphometric alterations correlated significantly with the known expression patterns of PCDH19 (r value = -0.26, p spin = 0.092). PCDH19 encephalopathy represents a model of genetically determined neural network based neuropsychiatric disease in which quantitative MRI-based findings correlate with the severity of clinical manifestations and had have a potential predictive value if analyzed early.