Functional Connectivity Patterns and the Role of 5-HTTLPR Polymorphism on Network Architecture in Female Patients With Anorexia Nervosa

Abstract

IntroductionRecent neuroimaging studies suggest that anorexia nervosa (AN) symptoms emerge from failures in the relationships between spatially distributed networks that support different cognitive, emotional, and somatosensory functions. The 5-HTTLPR genotype has been shown to modulate all these abilities in AN, as well as the connectivity patterns between brain regions that support their functioning. This study aims at exploring the presence of any difference in functional connectome properties between AN patients and healthy controls (HC) by means of graph theory tools. The effect of 5-HTTLPR genotype on regional and global network characteristics in AN and HC was also explored.MethodsA sample of 74 subjects (38 HC, 36 AN) underwent a resting state functional magnetic resonance imaging and was genotyped for 5-HTTLPR polymorphism. Comparisons of network properties were made between the AN and HC groups and, within each group, between 5-HTTLPR carriers of low-functioning alleles and carriers of the long–long genotype.ResultsPatients with AN displayed lower network clustering than HC (p = 0.04 at Mann–Whitney U test). Based on both degree and betweenness, a different distribution of network hubs emerged in the two groups. In particular, the anterior part of the anterior cingulate cortex was a hub only in the patient group. A correlation emerged between differences in brain volumes between patients and HC and differences in degree values of basal ganglia, nodes in the insula, and those in the parietal cortex. Carriers of the short allele of the 5-HTTLPR polymorphism were characterized by lower small-world properties (p = 0.027) and modularity (p = 0.031) in the patient group, and a trend toward higher modularity (p = 0.033) and small-world values (p = 0.123) in the HC group.DiscussionPatients with AN showed differences in hubs distribution, providing evidence of the presence of a different functional architectural backbone in this group. Since some correlation emerged between different degree values of nodes and differences in volumes, further longitudinal studies are warranted to better understand the role of malnutrition on brain network architecture. The opposite effects of 5-HTTLPR polymorphism on global network characteristics in the two groups suggest an interaction of the short allele and malnutrition in modulating brain network properties.

Shift Toward Randomness in Brain Networks of Patients With Anorexia Nervosa: The Role of Malnutrition

“…The decrease in resilience is more severe in patients who reached very low BMI and showed a relationship with variations in cortical volumes, especially in the parietal cortex. It is noteworthy that a reduced clustering coefficient compared to healthy women has been found in the same sample exploring the functional connectome ( Collantoni et al, 2019a ) and in an independent sample of patients with AN ( Geisler et al, 2018 ).…”

“…Connectomic approaches have been recently used with both functional and anatomical data in different psychiatric disorders such as schizophrenia, major depressive disorder, obsessive–compulsive disorder, and attention-deficit/hyperactivity disorder ( Rubinov and Bullmore, 2013 ; Taylor, 2014 ; Sidlauskaite et al, 2015 ). Studies that evaluated network architecture in AN have been focused on the covariance patterns between cortical structural data and functional connectivity measures, revealing the presence of imbalances in segregation and integration properties of brain connectome ( Geisler et al, 2018 ; Collantoni et al, 2019a , b ). Interestingly, the studies evaluating cortical morphological and functional connectivity patterns did not report consistent findings in terms of segregation and integration.…”

Brain networks in eating disorders: a systematic review of graph theory studies

“…Most studies including AN-a participants (i.e., five) analyzed resting-state functional connectivity (FC) graphs [19][20][21][22][23]. In three instances, global topological features resulted altered.…”

Brain functional network alterations caused by a strong desire to void in healthy adults: a graph theory analysis study

“…The graph theory analysis (GTA), as a data-driven approach, describes the brain network as a collection of nodes and edges, which can reveal meaningful information about the topologic architecture of human brain networks by calculating a series of global and local parameters such as small-world parameters and network efficiency. [10][11][12][13][14][15][16] GTA has been widely used to study the brain functional topological structure of neurological and mental diseases, and it has been found that the human brain has small-world properties, which may be disturbed by diseases. 14,17,18 In this study, we used resting-state fMRI to determine the whole-brain FC changes and topologic property alterations of the brain functional network provoked by a strong desire to void in healthy adults, which could serve as a baseline for understanding the pathologic process underlying bladder dysfunction.…”

“…[10][11][12][13][14][15][16] GTA has been widely used to study the brain functional topological structure of neurological and mental diseases, and it has been found that the human brain has small-world properties, which may be disturbed by diseases. 14,17,18 In this study, we used resting-state fMRI to determine the whole-brain FC changes and topologic property alterations of the brain functional network provoked by a strong desire to void in healthy adults, which could serve as a baseline for understanding the pathologic process underlying bladder dysfunction.…”