Most studies provide strong support for an etiologic role of stressful life events in irritable bowel syndrome (IBS). Consistent with the observations in both patients and doctors that psychosocial disturbances seem to precede the onset or exacerbation of gut symptoms, researches have consistently found high levels of emotional distress in a proportion of patients with IBS and other functional gastrointestinal disorders. Moreover, a variety of other potentially psychiatric diseases such as anxiety, depression, and sleep disorder also coexist frequently with IBS. In recent literatures, some studies have shown altered mechanoelastic properties such as colonic tone, compliance, and accommodation. The demonstrated differences in colonic compliance and accommodation suggest peripheral neuromuscular substrate contributing to the pathogenesis of IBS. However, until now, attention has focused on the disturbances of visceral hypersensitivity rather than on gastrointestinal motor function as a hallmark of IBS pathophysiology. But not all IBS patients show decreased rectosigmoid pain thresholds. Recent advances in brain imaging have allowed investigators to measure changes in regional cerebral blood flow during stimulation. Those methods have extended our understanding of brain function and brain-gut interaction. IBS is characterized by hypersensitivity to visceral sensation and augmented response to stress. Studies on the disorders of sensori-motor function have also contributed to understand the knowledge of neurotransmitters involved in the function of the enteric nervous system and to identify targets for the development of new treatments for IBS.
Brain/physiology ; Humans ; Intestines/innervation/physiopathology ; Irritable Bowel Syndrome/physiopathology/*psychology ; Stress, Psychological/complications/physiopathology

Female ; Humans ; Menstruation ; physiology ; Menstruation Disturbances ; epidemiology ; etiology ; Occupational Health ; Stress, Psychological ; complications ; epidemiology ; physiopathology

Chronic stress is generally accepted as the main risk factor in the development of cognitive decline; however, the underlying mechanisms remain unclear. Previous data have demonstrated that the levels of homocysteine (Hcy) are significantly elevated in the plasma of stressed animals, which suggests that Hcy is associated with stress and cognitive decline. To test this hypothesis, we analyzed the cognitive function, plasma concentrations of Hcy, and brain-derived neurotropic factor (BDNF) levels in rats undergoing chronic unpredicted mild stress (CUMS). The results showed that decreased cognitive behavioral performance and decreased BDNF transcription and protein expression were correlated with hyperhomocysteinemia (HHcy) levels in stressed rats. Diet-induced HHcy mimicked the cognitive decline and BDNF downregulation in the same manner as CUMS, while Hcy reduction (by means of vitamin B complex supplements) alleviated the cognitive deficits and BDNF reduction in CUMS rats. Furthermore, we also found that both stress and HHcy disturbed the DNA methylation process in the brain and induced DNA hypermethylation in the BDNF promoter. In contrast, control of Hcy blocked BDNF promoter methylation and upregulated BDNF levels in the brain. These results imply the possibility of a causal role of Hcy in stress-induced cognitive decline. We also used ten-eleven translocation (TET1), an enzyme that induces DNA demethylation, to verify the involvement of Hcy and DNA methylation in the regulation of BDNF expression and the development of stress-related cognitive decline. The data showed that TET1-expressing viral injection into the hippocampus inhibited BDNF promoter methylation and significantly mitigated the cognitive decline in HHcy rats. Taken together, novel evidence from the present study suggests that Hcy is likely involved in chronic stress-induced BDNF reduction and related cognitive deficits. In addition, the negative side-effects of HHcy may be associated with Hcy-induced DNA hypermethylation in the BDNF promoter. The results also suggest the possibility of Hcy as a target for therapy and the potential value of vitamin B intake in preventing stress-induced cognitive decline.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Cognitive Dysfunction/complications* ; DNA Methylation ; Homocysteine/metabolism* ; Hyperhomocysteinemia/metabolism* ; Rats ; Stress, Psychological/physiopathology*

OBJECTIVETo evaluate the nitric oxide (NO) levels in rat brain cortex and hippocampus after chronic mild stress.

METHODSSixteen male Sprague-Dawley rats were allocated into control group and model group randomly. Model rats were induced by consecutive chronic mild stress; weight gain, open field test and sucrose solution consumption were investigated before and after procedure. Nitric oxide contents in prefrontal cortex and hippocampus were determined by spectrophotometric assays.

RESULTDecreased locomotion, loss of interest and anhedonia were observed in chronic mild stress rat model group. Nitric oxide contents in prefrontal cortex and hippocampus were significantly higher in chronic mild stress group [(31.00 +/-2.55)nmol/mg.pro and (38.11 +/-1.73)nmol/mg.pro, respectively] than those in control group [(26.97 +/-1.38)nmol/mg.pro and (36.06 +/-0.87)nmol/mg.pro, respectively] (P <0.05).

CONCLUSIONChronic stress can stimulate NO release, and dysfunction of nitric oxide pathway may be involved in development of depression.

Animals ; Cerebral Cortex ; metabolism ; Depression ; etiology ; physiopathology ; Hippocampus ; metabolism ; Male ; Motor Activity ; physiology ; Nitric Oxide ; biosynthesis ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological ; complications ; physiopathology

Autistic Disorder ; complications ; psychology ; Child ; Child Development ; Communication ; Down Syndrome ; complications ; physiopathology ; psychology ; Follow-Up Studies ; Humans ; Interpersonal Relations ; Male ; Play and Playthings ; Singapore ; Social Behavior ; Stress, Psychological ; psychology

PURPOSE: Our study aimed to examine the relationship between intelligence and health-related quality of life (HRQOL) in children (6-13 years old) diagnosed as having a brain tumor. MATERIALS AND METHODS: We administered a Korean version of the Wechsler Intelligence Scale for Children-III, the Pediatric Quality of Life Inventory, version 4.0 (PedsQL), the Korean version of the Parenting Stress Index-Short Form, and the Korean Version of the Parenting Sense of Competence (K-PSOC) scale before or after initial radiotherapy (T1) and after treatment termination (T2). In total, 13 patients completed both the T1 and T2 interviews. RESULTS: Scores significantly declined between T1 and T2 on the full-scale intelligence quotients (FIQ), verbal intelligence quotients (VIQ), performance intelligence quotients (PIQ), similarity and coding tests, as well as the K-PSOC, which measures parental anxiety. FIQ scores at T1 were correlated with the self-reported PedsQL total scores (r=0.739) and the parent proxy-report PedsQL scores for school functioning (r=0.706) at T2. Also, the FIQ scores at T2 were correlated with the self-reported PedsQL total scores (r=0.748) and scores for physical health (r=0.728) at T2. CONCLUSION: The cognitive ability and intelligence level of the patients significantly declined between on and off treatment periods, and higher intelligence functioning at both on and off treatment was correlated with long-term higher HRQOL. Further investigations that monitor intelligence, HRQOL and parenting stress over a longer period, using a greater number of participants, are needed.
Adolescent ; Anxiety ; Brain Neoplasms/complications/physiopathology/*psychology ; Child ; *Cognition ; Female ; Humans ; Intelligence Tests ; Longitudinal Studies ; Male ; Parenting ; Parents/psychology ; Prospective Studies ; *Quality of Life ; Stress, Psychological/*diagnosis ; Time Factors

PURPOSE: Fatigue is the third most common "extraintestinal" complaint of patients with irritable bowel syndrome (IBS), but it is still poorly understood. This study aimed to review characteristics of IBS-associated fatigue and to examine pooled frequency, severity of fatigue, and correlations of related factors with fatigue in IBS via meta-analyses. METHODS: Publications were searched in eight databases from 1995 to 2014. Random effects meta-analyses were applied with standard error, weighted effect size, and correlation-based measure of effect size. RESULTS: Twenty-four studies were included in systematic review. Seventeen studies were used for meta-analyses (2 studies were excluded in the frequency of fatigue analysis due to data unavailability). Using "tiredness" to define fatigue, and Fatigue Impact Scale to assess fatigue were the most frequently used across the studies. Gastrointestinal symptoms, psychological distress, and health-related quality of life were the most common correlates with fatigue. The pooled frequency of fatigue was 54.2% [95% confidence interval (38.5, 69.4)]. Metaregression on the frequency of fatigue showed positive and significant relations with tertiary care settings, female sex, and younger age. There was a negatively moderate relationship between the severity of fatigue and health-related quality of life score (correlation-based measure of effect size: -.378). CONCLUSIONS: Fatigue is prevalent among patients with IBS and commonly co-occurs with other symptoms. This is the first study to fully examine fatigue in IBS, which shed light on the comprehensive management of fatigue in this patient group. Future research is warranted to further explore fatigue-related factors and underlying mechanisms of fatigue in IBS.
Adult ; Age Factors ; Aged ; Fatigue/*etiology/*nursing ; Female ; Humans ; Irritable Bowel Syndrome/*complications/*physiopathology ; Male ; Middle Aged ; Prevalence ; *Quality of Life ; Severity of Illness Index ; Sex Factors ; Stress, Psychological

OBJECTIVETo study the effects of kaixinsan on behavior and expression of p-CREB in hippocampus of the chronic stress rats.

METHODThe male Wistar rats which gained the similar scores by Open-field test were selected, then the depression model rat was produced by separation and chronic unpredictable mild stress. Open-field test was performed to detect the behavior of rats and immunohistochemistry was used to observe the changes of p-CREB expression in hippocampus.

RESULTOn the 22nd day, the body weight and sacchar-intake of the depression model rats were all lower than those of the normal rats and the body weight and sacchar-intake of the rats treated by drugs were higher compared with model rats (P < 0.01). The depressive behavior in kaixinsan 4 g x kg(-1) group was significantly improved compared with the model group, the crossing scores and rearing scores were all increased (P < 0.01) and the expression of p-CREB in CA1, CA3 and DG in hippocampus was higher than that in the model group (P < 0.05 and P < 0.01).

CONCLUSIONKaixinsan might improve depressive behavior by increasing expression of p-CREB in CA1, CA3 and DG in hippocampus of the chronic stress rats.

Animals ; Antidepressive Agents ; pharmacology ; Behavior, Animal ; drug effects ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Depression ; etiology ; physiopathology ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Hippocampus ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Stress, Psychological ; complications

OBJECTIVETo explore the effect of food allergy (FA) on the development of visceralgia sensibility and the substance P (SP) expression in colon of developing rats with FA.

METHODThree-week old female Sprague-Dawley (SD) rats were randomly divided into two groups (n = 10 in each). The rats in FA group were sensitized with ovalbumin (OVA) 40 µg and Al(OH)3 1 mg suspension solution (0.2 ml) intraperitoneal (i.p.) injection on day 0, only OVA 40 µg solution i.p. on day 2, 4, 7, 9, 11, respectively, and the rats were challenged by gavage with OVA solution 30 mg (2 ml) on day 20, 24, 28, 30. The rats in non-sensitized (NS) group were not challenged except handled in the same ways. The serum OVA-IgE were determined by enzyme-linked immuno sorbent assay (ELISA) on day 0, 30. Jejunum segments were used to observe morphological structure, the expression of eosinophils, and the density and the percentage of degranulation of mast cells (MC). The rats were appraised for the pain sensibility of intestinal tract under colorectal distension irritation by the electrophysiological method on external oblique in the 18-24 hr after the last challenge. Colons were used to analyze the expression of SP through immunohistochemical staining and computer image analyzing system.

RESULTThe serum OVA-IgE concentration and the eosinophils, mast cell, the percentage of mast cells degranulation in FA group were more than NS group (P < 0.01). The amplitudes of spike external oblique muscle of abdomen (EOMA, µV) of the FA group under the colorectal distension (CRD) pressures at 0, 15, 30, 45, 60, 75 mm Hg were (17.74 ± 0.72), (18.63 ± 1.72), (22.55 ± 1.70), (28.63 ± 7.00), (33.97 ± 7.34), (37.26 ± 8.40), and (17.43 ± 1.18), (17.27 ± 1.16), (17.73 ± 1.42), (19.55 ± 3.54), (23.29 ± 5.46), (25.20 ± 4.75) in NS group. With the CRD pressure increased, the amplitudes of spike EOMA increased significantly. There were significant differences between groups under the CRD pressures at 30, 45, 60, 75 mm Hg (F = 47.470, 13.367, 13.317, 15.390, P < 0.01). The expressions of colons SP in FA group and NS group are 247.12 ± 90.83 and 103.90 ± 58.94, respectively (t = 4.183, P < 0.01).

CONCLUSIONSensitization through i.p. pathway and challenge by gavage with OVA in early life could result in FA in young SD rats. FA in early life enabled the amplitudes of spike EOMA and the expression of colons SP increase significantly. It may be related to increase in amount and degranulation of MC and SP abnormal expression in colon, which could lead to the development of visceralgia sensibility.

Animals ; Colonic Diseases, Functional ; metabolism ; Disease Models, Animal ; Electrophysiology ; Female ; Food Hypersensitivity ; complications ; metabolism ; Hyperalgesia ; etiology ; metabolism ; physiopathology ; Intestinal Mucosa ; metabolism ; pathology ; Mast Cells ; metabolism ; Ovalbumin ; adverse effects ; Pain Threshold ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological ; Substance P ; metabolism

OBJECTIVETo investigate the effects of prenatal stress (PNS) on kinetic properties of high-voltage-activated (HVA) Ca(2+) channel in freshly isolated offspring rat hippocampal CA3 pyramidal neurons.

METHODSThe pregnant rats were exposed to restraint stress, and the hippocampal CA3 pyramidal neurons were freshly isolated from the offspring rats to record voltage-gate Ca(2+) channel currents in these neurons using whole-cell configuration of patch-clamp technique.

RESULTSPNS significantly increased HVA calcium current density and integral current but did not alter the steady-state activation and steady-state inactivation properties of HVA Ca(2+) channel in the offspring rat CA3 neurons. The maximal HVA calcium current density was -40.89-/+0.31 pA/pF in the control group (n=10) and -49.44-/+0.37 pA/pF in PNS group (n=8, P<0.01). The maximal integral current of the HVA Ca(2+) channel was 106.81-/+4.20 nA*ms in the control group (n=10) and 133.49-/+2.59 nA*ms in the PNS group (n=8, P<0.01).

CONCLUSIONMaternal exposure to stress during the critical phase of pregnancy may result in long-lasting effects on the ion channels of the hippocampal neurons in the offspring rats.

Animals ; Animals, Newborn ; Calcium Channels ; physiology ; Female ; Hippocampus ; cytology ; Kinetics ; Male ; Membrane Potentials ; physiology ; Patch-Clamp Techniques ; Pregnancy ; Pregnancy Complications ; psychology ; Pyramidal Cells ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley ; Restraint, Physical ; psychology ; Stress, Psychological ; physiopathology