Biopsychosocial Model of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common chronic disorder seen in gastroenterology and primary care practice. It is characterized by recurrent abdominal pain or discomfort associated with disturbed bowel function. It is a heterogeneous disorder with varying treatments, and in this regard physicians sometimes struggle with finding the optimal approach to management of patients with IBS. This disorder induces high health care costs and variably reduces health-related quality of life. IBS is in the class of functional gastrointestinal disorders, and results from dysregulation of central and enteric nervous system interactions. Psychosocial factors are closely related to their gut physiology, associated cognitions, symptom manifestations and illness behavior. Therefore, it is important for the physician to recognize the psychosocial issues of patients with IBS and in addition to build a good patient-physician relationship in order to optimize treatment. This review focuses on the interaction between psychological and physiological factors associated with IBS by using a biopsychosocial model. In this article, we describe (1) the predisposing psychological features seen in early life; (2) the psychological factors associated with life stress, the symptom presentation, and their associated coping patterns; (3) gut pathophysiology with emphasis on disturbances in motility, visceral hypersensitivity and brain-gut interactions; and finally (4) the clinical outcomes and effective treatments including psychotherapeutic methods

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

Background and aimsThe 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.MethodsTwenty-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).ResultsDuring 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.ConclusionIn 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

Changes in salivary physiological stress markers induced by muscle stretching in patients with irritable bowel syndrome

<p>Abstract</p> <p>Background</p> <p>Psychophysiological processing has been reported to play a crucial role in irritable bowel syndrome (IBS) but there has been no report on modulation of the stress marker chromogranin A (CgA) resulting from muscle stretching. We hypothesized that abdominal muscle stretching as a passive operation would have a beneficial effect on a biochemical index of the activity of the sympathetic/adrenomedullary system (salivary CgA) and anxiety.</p> <p>Methods</p> <p>Fifteen control and eighteen untreated IBS subjects underwent experimental abdominal muscle stretching for 4 min. Subjects relaxed in a supine position with their knees fully flexed while their pelvic and trunk rotation was passively and slowly moved from 0 degrees of abdominal rotation to about 90 degrees or the point where the subject reported feeling discomfort.</p> <p>Changes in the Gastrointestinal Symptoms Rating Scale (GSRS), State Trait Anxiety Inventory (STAI), Self-rating Depression Scale (SDS), ordinate scale and salivary CgA levels were compared between controls and IBS subjects before and after stretching. A three-factor analysis of variance (ANOVA) with period (before vs. after) as the within-subject factor and group (IBS vs. Control), and sex (men vs. female) as the between-subject factors was carried out on salivary CgA.</p> <p>Results</p> <p>CgA showed significant interactions between period and groups (F[1, 31] = 4.89, p = 0.03), and between groups and sex (F[1, 31] = 4.73, p = 0.03). Interactions between period and sex of CgA secretion were not shown (F[1, 3] = 2.60, p = 0.12). At the baseline, salivary CgA in IBS subjects (36.7 ± 5.9 pmol/mg) was significantly higher than in controls (19.9 ± 5.5 pmol/mg, p < 0.05). After the stretching, salivary CgA significantly decreased in the IBS group (25.5 ± 4.5 pmol/mg), and this value did not differ from that in controls (18.6 ± 3.9 pmol/mg).</p> <p>Conclusion</p> <p>Our results suggest the possibility of improving IBS pathophysiology by passive abdominal muscle stretching as indicated by CgA, a biochemical index of the activity of the sympathetic/adrenomedullary system.</p

Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation

Recent reports indicate that refractory central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC) are improved by high-dose gefitinib or erlotinib administration. We describe a Japanese woman with NSCLC and CNS metastases who was resistant to 75 mg daily erlotinib, but the metastases were improved by 150 mg daily erlotinib. We investigated the plasma and CSF concentrations of erlotinib at each dose as well as the correlation between the plasma and CSF concentrations of erlotinib