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S Fukudo,
M Kanazawa,
T Mizuno,
T Hamaguchi,
M Kano,
S Watanabe,
Y Sagami,
T Shoji, Y Endo,
M Hongo,
Y Itoyama,
K Yanai,
M Tashiro,
M Aoki
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ABSTRACT: Determining the gene that plays a key role in brain-gut interactions is a crucial step for clarifying the pathophysiology of irritable bowel syndrome (IBS). We previously reported that the 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is related to anxiety in subjects with IBS. The amygdala is more activated during fearful face recognition in individuals with the s allele of 5-HTTLPR. Here, we tested our hypothesis that 5-HTTLPR differentially activates brain regions with colorectal distention in humans.
We enrolled 28 subjects without any organic disease. The study was approved by the Ethics Committee and all subjects gave written informed consent. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Age, sex, diagnosis-matched individuals with the s/s genotype (n=14) and individuals with the l allele (genotypes l/s, l/l, l/extra-l, n=14) were compared. A barostat bag was inserted to the colorectum and was intermittently inflated with no (0 mm Hg), mild (20 mm Hg), or intense (40 mm Hg) stimulation on a random order. Radioactive H2[(15-)O] saline was injected at bag inflation and then positron emission tomography was performed. Changes in rCBF were analyzed using statistical parametric mapping.
Individuals with the s/s genotype showed a significantly larger increase in rCBF by colorectal distention from 0 mm Hg to 40 mm Hg than individuals with the l allele. The significantly more activated brain regions in individuals with the s/s genotype were the left anterior cingulate cortex and right parahippocampal gyrus (p<0.0001). The increase in rCBF by colorectal distention of 20 mm Hg compared with 0 mm Hg was significantly larger in the left orbitofrontal cortex of individuals with the s/s genotype than that of individuals with the l allele (p<0.0001).
These data suggest that individuals with a weak function of serotonin transporter respond to gut signals more in emotion-regulating brain regions. Functional gene polymorphism may partially predict the individual effect of a selective serotonin reuptake inhibitor on visceral pain.
NeuroImage 06/2009; 47(3):946-51. · 5.89 Impact Factor
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T. Mizuno,
M. Aoki,
Y. Shimada,
M. Inoue,
K. Nakaya,
T. Takahashi,
Y. Itoyama,
M. Kanazawa,
A. Utsumi, Y. Endo,
T. Nomura,
M. Hiratsuka,
M. Mizugaki,
J. Goto,
M. Hongo,
S. Fukudo
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ABSTRACT: OBJECTIVE: The objective of this study was to verify the hypothesis that variation of the serotonin transporter gene promoter region (5-HTTLPR) is associated with sensitivity to stress. METHODS: Genotyping of 5-HTTLPR and evaluation of emotional states were performed on 194 participants. Participants' emotional states were evaluated using the Perceived-Stress Scale (PSS), the State-Trait Anxiety Inventory (STAI), and the Self-rating Depression Scale (SDS). RESULTS: There was significant GenderxGenotype interaction in STAI (state, P<.05; trait, P<.05). Females with the l/s genotype showed higher anxiety than those with the s/s genotype in both state and trait anxiety. Oppositely, males with the s/s genotype showed higher anxiety than those with the l/s genotype. CONCLUSION: On all emotional scales, females with the l/s genotype showed high scores, contrary to males with the same genotype. Therefore, our results suggest that 5-HTTLPR l allele may be one pathway that activates negative emotion in females but acts contrary in males.
Journal of psychosomatic research. 01/2006; 60(1):91-7.
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ABSTRACT: Functional gastrointestinal (GI) disorders are common in primary care. However, proper pharmacological approaches have not yet been established. The reason for a lack of proper approaches may be attributable to the lack in clarity of their pathogenesis and pathophysiology. Meta-analysis of pharmacological approaches to functional GI disorders failed to identify the solid cluster of patients' symptoms.
The aim of this study is to assess the perspective of primary care doctors concerning prescriptions for functional GI symptoms, evaluate the efficacy of the drugs prescribed, and the need for medication for these symptoms.
Questionnaires were sent to primary care doctors, and a total of 149 responses were obtained. Efficacy of each medication was evaluated by the number of doctors favouring the category, and the respective impressions of prescriptions given.
Symptoms of heartburn were well controlled by anti-secretory drugs (H2RAs and PPIs), while appetite loss and abdominal gurgling were not controlled by any medications.
This survey reveals differences in need for various prescription drugs in functional GI symptoms.
Alimentary Pharmacology & Therapeutics 07/2005; 21 Suppl 2:47-54. · 3.77 Impact Factor
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ABSTRACT: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients.
Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 micro g/kg).
ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH.
Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.
Gut 08/2004; 53(7):958-64. · 10.11 Impact Factor
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M Yoshizawa,
M Tashiro,
S Fukudo,
K Yanai,
A Utsumi,
M Kano,
M Karahashi, Y Endo,
J Morishita,
Y Sato,
M Adachi,
M Itoh,
M Hongo
