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Serotonin Transporter Gene Polymorphism Modulates Activity and Connectivity within an Emotional Arousal Network of Healthy Men during an Aversive Visceral Stimulus.

Kilpatrick LA, Mayer EA, Labus JS, Gupta A, Hamaguchi T, Mizuno T, Komuro H, Kano M, Kanazawa M, Aoki M, Fukudo S - PLoS ONE (2015)

Bottom Line: Changes in regional cerebral blood flow (rCBF) were analyzed using partial least squares (PLS) and structural equation modeling (SEM).During inflation, subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers.In male Japanese subjects, individuals with s/s genotype show alterations in the connectivity of brain regions involved in stress responsiveness and emotion regulation during aversive visceral stimuli compared to those with l carriers.

View Article: PubMed Central - PubMed

Affiliation: Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive Diseases, David Geffen School of Medicine at University of California at Los Angeles (UCLA), Los Angeles, California, United States of America.

ABSTRACT

Background and aims: The 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) has been linked to increased stress responsiveness and negative emotional states. During fearful face recognition individuals with the s allele of 5-HTTLPR show greater amygdala activation. We aimed to test the hypothesis that the 5-HTTLPR polymorphism differentially affects connectivity within brain networks during an aversive visceral stimulus.

Methods: Twenty-three healthy male subjects were enrolled. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Subjects with the s/s genotype (n = 13) were compared to those with the l allele (genotypes l/s, l/l, n = 10). Controlled rectal distension from 0 to 40 mmHg was delivered in random order using a barostat. Radioactive H2[15-O] saline was injected at time of distension followed by positron emission tomography (PET). Changes in regional cerebral blood flow (rCBF) were analyzed using partial least squares (PLS) and structural equation modeling (SEM).

Results: During baseline, subjects with s/s genotype demonstrated a significantly increased negative influence of pregenual ACC (pACC) on amygdala activity compared to l-carriers. During inflation, subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers.

Conclusion: In male Japanese subjects, individuals with s/s genotype show alterations in the connectivity of brain regions involved in stress responsiveness and emotion regulation during aversive visceral stimuli compared to those with l carriers.

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Related in: MedlinePlus

Connectivity Analysis for Baseline and Colorectal Distention.Chi square difference statistics during baseline and colorectal distention. λ2 difference > 3.84 is considered significant and is denoted in red. λ2 difference < 3.84 is considered non-significant and is denoted in blue. Regions: AMYG, amygdala; HIPP, hippocampus, sgACC, subgenual cingulate cortex; pACC, pregenual anterior cingulate cortex; mPFC, medial prefrontal cortex; dlPFC, dorsolateral prefrontal cortex; vlPFC, ventro-lateral prefrontal cortex; aMCC, anterior mid cingulate cortex; PCC, posterior cingulate cortex; aINS, anterior insula; mINS, mid insula; pINS, posterior insula.
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pone.0123183.g002: Connectivity Analysis for Baseline and Colorectal Distention.Chi square difference statistics during baseline and colorectal distention. λ2 difference > 3.84 is considered significant and is denoted in red. λ2 difference < 3.84 is considered non-significant and is denoted in blue. Regions: AMYG, amygdala; HIPP, hippocampus, sgACC, subgenual cingulate cortex; pACC, pregenual anterior cingulate cortex; mPFC, medial prefrontal cortex; dlPFC, dorsolateral prefrontal cortex; vlPFC, ventro-lateral prefrontal cortex; aMCC, anterior mid cingulate cortex; PCC, posterior cingulate cortex; aINS, anterior insula; mINS, mid insula; pINS, posterior insula.

Mentions: During inflation, male subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers. In addition, subjects with s/s genotype demonstrated a weak negative influence of mPFC on amygdala activity while l-carriers demonstrated a strong positive influence of mPFC on amygdala activity. Fig 1 and Fig 2 summarize the results from the connectivity analysis.


Serotonin Transporter Gene Polymorphism Modulates Activity and Connectivity within an Emotional Arousal Network of Healthy Men during an Aversive Visceral Stimulus.

Kilpatrick LA, Mayer EA, Labus JS, Gupta A, Hamaguchi T, Mizuno T, Komuro H, Kano M, Kanazawa M, Aoki M, Fukudo S - PLoS ONE (2015)

Connectivity Analysis for Baseline and Colorectal Distention.Chi square difference statistics during baseline and colorectal distention. λ2 difference > 3.84 is considered significant and is denoted in red. λ2 difference < 3.84 is considered non-significant and is denoted in blue. Regions: AMYG, amygdala; HIPP, hippocampus, sgACC, subgenual cingulate cortex; pACC, pregenual anterior cingulate cortex; mPFC, medial prefrontal cortex; dlPFC, dorsolateral prefrontal cortex; vlPFC, ventro-lateral prefrontal cortex; aMCC, anterior mid cingulate cortex; PCC, posterior cingulate cortex; aINS, anterior insula; mINS, mid insula; pINS, posterior insula.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4404144&req=5

pone.0123183.g002: Connectivity Analysis for Baseline and Colorectal Distention.Chi square difference statistics during baseline and colorectal distention. λ2 difference > 3.84 is considered significant and is denoted in red. λ2 difference < 3.84 is considered non-significant and is denoted in blue. Regions: AMYG, amygdala; HIPP, hippocampus, sgACC, subgenual cingulate cortex; pACC, pregenual anterior cingulate cortex; mPFC, medial prefrontal cortex; dlPFC, dorsolateral prefrontal cortex; vlPFC, ventro-lateral prefrontal cortex; aMCC, anterior mid cingulate cortex; PCC, posterior cingulate cortex; aINS, anterior insula; mINS, mid insula; pINS, posterior insula.
Mentions: During inflation, male subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers. In addition, subjects with s/s genotype demonstrated a weak negative influence of mPFC on amygdala activity while l-carriers demonstrated a strong positive influence of mPFC on amygdala activity. Fig 1 and Fig 2 summarize the results from the connectivity analysis.

Bottom Line: Changes in regional cerebral blood flow (rCBF) were analyzed using partial least squares (PLS) and structural equation modeling (SEM).During inflation, subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers.In male Japanese subjects, individuals with s/s genotype show alterations in the connectivity of brain regions involved in stress responsiveness and emotion regulation during aversive visceral stimuli compared to those with l carriers.

View Article: PubMed Central - PubMed

Affiliation: Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive Diseases, David Geffen School of Medicine at University of California at Los Angeles (UCLA), Los Angeles, California, United States of America.

ABSTRACT

Background and aims: The 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) has been linked to increased stress responsiveness and negative emotional states. During fearful face recognition individuals with the s allele of 5-HTTLPR show greater amygdala activation. We aimed to test the hypothesis that the 5-HTTLPR polymorphism differentially affects connectivity within brain networks during an aversive visceral stimulus.

Methods: Twenty-three healthy male subjects were enrolled. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Subjects with the s/s genotype (n = 13) were compared to those with the l allele (genotypes l/s, l/l, n = 10). Controlled rectal distension from 0 to 40 mmHg was delivered in random order using a barostat. Radioactive H2[15-O] saline was injected at time of distension followed by positron emission tomography (PET). Changes in regional cerebral blood flow (rCBF) were analyzed using partial least squares (PLS) and structural equation modeling (SEM).

Results: During baseline, subjects with s/s genotype demonstrated a significantly increased negative influence of pregenual ACC (pACC) on amygdala activity compared to l-carriers. During inflation, subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers.

Conclusion: In male Japanese subjects, individuals with s/s genotype show alterations in the connectivity of brain regions involved in stress responsiveness and emotion regulation during aversive visceral stimuli compared to those with l carriers.

Show MeSH
Related in: MedlinePlus