Dataset Information

The 5-HTTLPR Polymorphism Affects Network-Based Functional Connectivity in the Visual-Limbic System in Healthy Adults.

ABSTRACT: The serotonin transporter-linked polymorphic region 5-HTTLPR is a key genetic regulator of 5-HTT expression in the human brain where the short allele S has been implicated in emotion dysregulation. However, the neural mechanism underlying the association between this variant and emotion processing is still unclear. Earlier studies suggested an effect of 5-HTTLPR on amygdala activation during emotional face processing. However, this association has been questioned in recent studies employing larger sample sizes and meta-analyses. Here, we examined a sample of 223 healthy subjects with a well-established fMRI emotional face processing task to (1) re-evaluate the association between 5-HTTLPR and amygdala activation, (2) explore potential network-based functional connectivity phenotypes for associations with 5-HTTLPR, and (3) probe the reliability, behavioral significance and potential structural confounds of the identified network phenotype. Our results revealed no significant effect of 5-HTTLPR on amygdala activation (P>0.79). However, the number of S alleles was significantly correlated with functional connectivity of a visual-limbic subnetwork (PFWE=0.03). The subnetwork cluster included brain regions that are pivotal to emotion regulation such as the hippocampus, orbitofrontal cortex, anterior cingulate gyrus, fusiform gyrus, and subcortex. Notably, individuals with lower subnetwork connectivity had significantly higher emotion suppression scores (P=0.01). Further, the connectivity metrics were test-retest reliable and independent from subnetwork gray matter volume and white matter anisotropy. Our data provide evidence for a functional network-based phenotype linking genetic variation in 5-HTTLPR to emotion regulation, and suggest that further critical evaluations of the association between 5-HTTLPR and amygdala activation are warranted.

SUBMITTER: Cao H

PROVIDER: S-EPMC5729553 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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The 5-HTTLPR Polymorphism Affects Network-Based Functional Connectivity in the Visual-Limbic System in Healthy Adults.

Cao Hengyi H Harneit Anais A Walter Henrik H Erk Susanne S Braun Urs U Moessnang Carolin C Geiger Lena S LS Zang Zhenxiang Z Mohnke Sebastian S Heinz Andreas A Romanczuk-Seiferth Nina N Mühleisen Thomas T Mattheisen Manuel M Witt Stephanie H SH Cichon Sven S Nöthen Markus M MM Rietschel Marcella M Meyer-Lindenberg Andreas A Tost Heike H

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20170607 2

The serotonin transporter-linked polymorphic region 5-HTTLPR is a key genetic regulator of 5-HTT expression in the human brain where the short allele S has been implicated in emotion dysregulation. However, the neural mechanism underlying the association between this variant and emotion processing is still unclear. Earlier studies suggested an effect of 5-HTTLPR on amygdala activation during emotional face processing. However, this association has been questioned in recent studies employing larg ...[more]

PMID: 28589968

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Project description: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.

Project description:Exposure to early life stress (ELS) is associated with a variety of detrimental psychological and neurodevelopmental effects. Importantly, ELS has been associated with regional alterations and aberrant connectivity in the structure and functioning of brain regions involved in emotion processing and self-regulation, creating vulnerability to mental health problems. However, longitudinal research regarding the impact of ELS on functional connectivity between brain regions in the default mode network (DMN) and fronto-limbic network (FLN), both implicated in emotion-related processes, is relatively scarce. Neuroimaging research on ELS has mostly focused on single nodes or bi-nodal connectivity instead of functional networks. We examined how ELS is associated with connectivity patterns within the DMN and FLN during rest in early adulthood. The participants (n = 86; 47 females) in the current functional magnetic resonance imaging (fMRI) study were young adults (18-21 years old) whose families had participated in a longitudinal study since pregnancy. ELS was assessed both prospectively (parental reports of family relationship problems and mental health problems during pregnancy and infancy) and retrospectively (self-reported adverse childhood experiences). Inter-subject representational similarity analysis (IS-RSA) and multivariate distance matrix regression (MDMR) were used to analyze the association between ELS and the chosen networks. The IS-RSA results suggested that prospective ELS was associated with complex alterations within the DMN, and that retrospective ELS was associated with alterations in the FLN. MDMR results, in turn, suggested that that retrospective ELS was associated with DMN connectivity. Mean connectivity of the DMN was also associated with retrospective ELS. Analyses further showed that ELS-related alterations in the FLN were associated with increased connectivity between the prefrontal and limbic regions, and between different prefrontal regions. These results suggest that exposure to ELS in infancy might have long-lasting influences on functional brain connectivity that persist until early adulthood. Our results also speak for the importance of differentiating prospective and retrospective assessment methods to understand the specific neurodevelopmental effects of ELS.

Project description:Split-belt treadmill walking allows researchers to understand how new gait patterns are acquired. Initially, the belts move at two different speeds, inducing asymmetric step lengths. As people adapt their gait on a split-belt treadmill, left and right step lengths become more symmetric over time. Upon returning to normal walking, step lengths become asymmetric in the opposite direction, indicating deadaptation. Then, upon re-exposure to the split belts, step length asymmetry is less than the asymmetry at the start of the initial exposure, indicating readaptation. Changes in step length symmetry are driven by changes in step timing and step position asymmetry. It is critical to understand what factors can promote step timing and position adaptation and therefore influence step length asymmetry. There is limited research regarding the role of visual feedback to improve gait adaptation. Using visual feedback to promote the adaptation of step timing or position may be useful of understanding temporal or spatial gait impairments. We measured gait adaptation, deadaptation, and readaptation in twenty-nine healthy young adults while they walked on a split-belt treadmill. One group received no feedback while adapting; one group received asymmetric real-time feedback about step timing while adapting; and the last group received asymmetric real-time feedback about step position while adapting. We measured step length difference (non-normalized asymmetry), step timing asymmetry, and step position asymmetry during adaptation, deadaptation, and readaptation on a split-belt treadmill. Regardless of feedback, participants adapted step length difference, indicating that walking with temporal or spatial visual feedback does not interfere with gait adaptation. Compared to the group that received no feedback, the group that received temporal feedback exhibited smaller early deadaptation step position asymmetry (p = 0.005). There was no effect of temporal or spatial feedback on step timing. The feedback groups adapted step timing and position similarly to walking without feedback. Future work should investigate whether asymmetric visual feedback also results in typical gait adaptation in populations with altered step timing or position control.

Dataset Information

The 5-HTTLPR Polymorphism Affects Network-Based Functional Connectivity in the Visual-Limbic System in Healthy Adults.

Publications

The 5-HTTLPR Polymorphism Affects Network-Based Functional Connectivity in the Visual-Limbic System in Healthy Adults.

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