Empirical studies indicate that alexithymia exacerbates physical illness. However, direct evidence to explain the mechanism of this exacerbation has not been provided. One hypothesis is that alexithymics amplify unpleasant internal signals. In the present study, we investigated how alexithymia influences sensitivity to visceral stimulation in human. In 45 non-clinical healthy subjects (34 males and 11 females), brain processing of visceral sensation induced by colonic distension was examined using H(2)(15)O positron emission tomography (PET). Subjective feeling evaluated on an ordinate scale and neuroendocrine response to stimuli were also measured. The degree of alexithymia was determined using the 20-item of Toronto alexithymia scale (TAS-20), and the correlation between reaction to stimuli and the scores of TAS-20 and its three subscales [difficulty to identify feelings (DIF), difficulty to describe feelings (DDF) and external oriented thinking (EOT)] was evaluated. Greater activation was observed during colonic distension in the pregenual anterior cingulate cortex, right insula and midbrain in the 10 (out of 45) subjects that were identified as alexithymic by TAS-20 scores larger than 61. TAS-20 scores positively correlated with both activity in the right insula and orbital gyrus and adrenaline levels in the blood in response to stimulation. Subjects with high scores of DIF perceived strong pain, urgency for defecation, stress, anxiety, and slight sleepiness. The present study demonstrates that alexithymia is associated with hypersensitivity to visceral stimulation. This finding supports the somatosensory amplification hypothesized in alexithymics and is important to elucidate the influence of alexithymia on brain-gut function, particularly to understand the pathophysiology of FGIDs (functional gastrointestinal disorders).

The visceral sensitivity index (VSI) is a useful self-report measure of the gastrointestinal symptom-specific anxiety (GSA) of patients with irritable bowel syndrome (IBS). Previous research has shown that worsening GSA in IBS patients is related to the severity of GI symptoms, suggesting that GSA is an important endpoint for intervention. However, there is currently no Japanese version of the VSI. We therefore translated the VSI into Japanese (VSI-J) and verified its reliability and validity. Participants were 349 university students aged 18 and 19 years and recruited from an academic class. We analyzed data from the VSI-J, Anxiety Sensitivity Index (ASI), Hospital Anxiety and Depression scale (HAD), and Irritable Bowel Syndrome Severity Index (IBS-SI). The internal consistency, stability, and factor structure of the VSI-J and its associations with anxiety, depression and severity measures were investigated. The factor structure of the VSI-J is unidimensional and similar to that of the original VSI (Cronbach's α = 0.93). Construct validity was demonstrated by significant correlations with ASI (r = 0.43, p < 0.0001), HAD-ANX (r = 0.19, p = 0.0003), and IBS-SI scores (r = 0.45, p < 0.0001). Furthermore, the VSI-J was a significant predictor of severity scores on the IBS-SI and demonstrated good discriminant (p < 0.0001) and incremental (p < 0.0001) validity. These findings suggest that the VSI-J is a reliable and valid measure of visceral sensitivity.

Objective: To test the hypothesis that gut stimulation provokes autonomic arousal via activation of regional cerebral cortices. How the human brain processes interoceptive signals and forms initial autonomic arousal is one of the key questions to be answered in research on emotion. Methods: Twelve healthy males participated in this study. A barostat bag was inserted in the rectum and intermittently inflated with 0, 20, or 40 mm Hg at random for 80 seconds. H₂¹⁵O positron emission tomography (PET) of the brain, electrocardiography, and blood sampling for catecholamines were performed. Changes in regional cerebral blood flow were interpreted using statistical parametric mapping. Results: Rectal distention with 40 mm Hg induced a significant increase in heart rate, low frequency (LF)/high frequency (HF) ratio of heart rate variability, and plasma adrenaline. Activated brain areas that were associated with increased heart rate during rectal distention were the right insula, right operculum, right dorsolateral prefrontal cortex, putamen, thalamus, periaqueductal gray, and cerebellum (p < .001, uncorrected), whereas those that were associated with an increased LF/HF ratio were the bilateral insula, putamen, thalamus, midbrain, pons, and cerebellum (p < .001, uncorrected). Activated brain areas that were associated with increased plasma adrenaline were the right insula, right orbitofrontal cortex, right parahippocampal gyrus, putamen, thalamus, periaqueductal gray, pons, and cerebellum (p < .001, uncorrected). Conclusion: Our results suggest that the right insula and the related body mapping regions may form the functional module of sympathetic arousal in response to gut stimulation. PET = positron emission tomography; rCBF = regional cerebral blood flow; SPM = statistical parametric mapping; BA = Brodmann’s area; ECG = electrocardiogram; HRV = heart rate variability; HF = high frequency component of HRV; LF = low frequency component of HRV; LF/HF = ratio of LF to HF; ANOVA = analysis of variance; MRI = magnetic resonance imaging.

Irritable bowel syndrome (IBS) often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H₂¹⁵O- positron emission tomography (PET) was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg) or saline (1:1) was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH), serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline) and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls) by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.