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: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.

Project description:BackgroundFemales are more likely to present with anxiety disorders such as post-traumatic stress disorder (PTSD) compared to males, which are associated with disrupted hippocampal integrity. Sex differences in the structure and function of hippocampus exist. Here, we examined sex differences in contextual pattern separation, functional connectivity, and activation of new neurons during fear memory.MethodsTwo-month-old male and female Sprague-Dawley rats were injected with the DNA synthesis markers, iododeoxyuridine (IdU) and chlorodeoxyuridine (CldU) 3 weeks and 4 weeks before perfusion, respectively. One week after CldU injection, the rats underwent a context discrimination task in which rats were placed in context A (shock) and context A' (no shock) every day for 12 days. On the test day, rats were placed in the shock context (context A) to measure fear memory and expression of zif268, an immediate early gene across 16 different limbic and reward regions. Repeated-measures or factorial analysis of variance was conducted on our variables of interest. Pearson product-moment calculations and principal component analyses on zif268 expression across regions were also performed.ResultsWe found that females, but not males, showed contextual discrimination during the last days of training. On the test day, both sexes displayed similar levels of freezing, indicating equivalent fear memory for context A. Despite similar fear memory, males showed more positive correlations of zif268 activation between the limbic regions and the striatum, whereas females showed more negative correlations among these regions. Females showed greater activation of the frontal cortex, dorsal CA1, and 3-week-old adult-born dentate granular cells compared to males.ConclusionsThese results highlight the importance of studying sex differences in fear memory and the contribution of adult neurogenesis to the neuronal network and may contribute to differences in susceptibility to fear-related disorders such as post-traumatic stress disorder. Highlights Female rats, but not male rats, show faster discrimination during a contextual pattern separation task. Three-week-old adult-born neurons are more active in response to fear memory in females compared to males. Females had greater neural activation compared to males in the frontal cortex and dorsal CA1 region of the hippocampus in response to fear memory. Males and females show distinct patterns in functional connectivity for fear memory across limbic regions. Males have many positive correlations between activated new neurons of different ages between the dorsal and ventral hippocampus, while females show more correlations between activated new neurons and other limbic regions.

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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