Chronic and acute stress and the prediction of major depression in women

Background: This study explored the relatively neglected role of chronic stress in major depression, examining the independent contributions of co‐occurring chronic and acute stress to depression, whether chronic stress predicts acute life events, and whether the two types of stress interact such that greater chronic stress confers greater sensitivity—or resistance—to the depressive effects of acute stressors. Methods: From a sample of 816 community women, those who had a major depression onset in the past 9 months and those without major depressive episodes (MDE) onset and with no history of current or recent dysthymic disorder were compared on interview‐based measures of antecedent acute and chronic stress. Chronic stress interviews rated objective stress in multiple everyday role domains, and acute stress was evaluated with contextual threat interviews. Results: MDE onset was significantly associated with both chronic and acute stress; chronic stress was also associated with the occurrence of acute events, and there was a trend suggesting that increased acute stress is more strongly associated with depression in those with high versus low chronic stress. Conclusions: Results suggest the importance of including assessment of chronic stress in fully understanding the extent and mechanisms of stress–depression relationships. Depression and Anxiety, 2009. Published 2009 Wiley‐Liss, Inc.     

抗抑郁剂对慢性应激大鼠脑内促肾上腺皮质激素释放因子CRFmRNA表达的影响

目的　研究慢性应激损伤大鼠下丘脑与皮层促肾上腺皮质激素释放因子 (CRF) m RNA表达及抗抑郁剂去甲丙咪嗪与氟西定对 CRFm RNA表达的影响。方法　采用不同应激方式交替持续应激 2 0 d,制成大鼠慢性应激损伤模型 ,用逆转录聚合酶联反应 (RT-PCR)方法测定大鼠下丘脑与皮层 CRFm RNA表达情况。结果　与对照组相比 ,慢性应激组 CRFm RNA在大鼠下丘脑与皮层的表达显著升高 ,而抗抑郁剂去甲丙咪嗪 (1 0 mg/kg,ip)与氟西定 (1 0 mg/kg,ip)可显著降低 CRFm RNA表达。结论　慢性应激引起大鼠下丘脑与皮层中 CRFm R-NA表达升高 ,抗抑郁剂去甲丙咪嗪与氟西定可能通过抑制 CRFm RNA表达的升高纠正下丘脑 -垂体 -肾上腺轴的超敏 ,发挥抗抑郁作用     

Novel insights in the role of peripheral corticotropin-releasing factor and mast cells in stress-induced visceral hypersensitivity

Visceral hypersensitivity is one of the hallmarks in irritable bowel syndrome (IBS) pathophysiology. Stress is well known to affect visceral sensitivity in humans and rodents, an effect which is associated in part with alterations of intestinal epithelial permeability in rodents. Although the pathophysiology of visceral hypersensitivity is still unclear, two key factors have been identified as playing a major role in its modulation, namely peripheral corticotropin-releasing factor (CRF) and mast cells. In a recent study in Neurogastroenterology and Motility, van den Wijngaard et al. demonstrate that the mast-cell dependent visceral hypersensitivity observed in maternally separated rats after an acute exposure to a psychological stress can be prevented but not reversed by the peripherally restricted CRF receptor antagonist, α-helical CRF(9-41). They further show that the preventive effect of the CRF receptor antagonist is linked to a stabilization of mast cells and maintenance of the epithelial barrier at the colonic level. These data suggest that post stress mast cell activation and subsequent visceral hypersensitivity are not targeted by peripheral CRF receptor antagonists. These novel insights in the role of peripheral CRF in the modulation of stress-induced visceral hypersensitivity add to our growing understanding of the mechanisms that may lie at the origin of visceral pain disturbances following stress and will contribute to enhance the development of drugs that may have potential therapeutic benefits for IBS patients.     

Type 1 corticotropin-releasing factor receptor expression reported in BAC transgenic mice: implications for reconciling ligand-receptor mismatch in the central corticotropin-releasing factor system

In addition to its established role in initiating the endocrine arm of the stress response, corticotropin-releasing factor (CRF) can act in the brain to modulate neural pathways that effect coordinated physiological and behavioral adjustments to stress. Although CRF is expressed in a set of interconnected limbic and autonomic cell groups implicated as primary sites of stress-related peptide action, most of these are lacking or impoverished in CRF receptor (CRFR) expression. Understanding the distribution of functional receptor expression has been hindered by the low resolution of ligand binding approaches and the lack of specific antisera, which have supported immunolocalizations at odds with analyses at the mRNA level. We have generated a transgenic mouse that shows expression of the principal, or type 1, CRFR (CRFR1). This mouse expresses GFP in a cellular distribution that largely mimics that of CRFR1 mRNA and is extensively colocalized with it in individual neurons. GFP-labeled cells display indices of activation (Fos induction) in response to central CRF injection. At the cellular level, GFP labeling marks somatic and proximal dendritic morphology with high resolution and is also localized to axonal projections of at least some labeled cell groups. This includes a presence in synaptic inputs to central autonomic structures such as the central amygdalar nucleus, which is implicated as a stress-related site of CRF action, but lacks cellular CRFR1 expression. These findings validate a new tool for pursuing the role of central CRFR signaling in stress adaptation and suggest means by which the pervasive ligand-receptor mismatch in this system may be reconciled.     

Altered regulation of gene and protein expression of hypothalamic-pituitary-adrenal axis components in an immature rat model of chronic stress

Chronic stress early in postnatal life influences hormonal and behavioural responses to stress persistently, but the mechanisms and molecular cascades that are involved in this process have not been clarified. To approach these issues, a chronic stress paradigm for the neonatal rat, using limited bedding material to alter the cage environment, was devised. In 9-day-old rats subjected to this chronic stress for 1 week, significant and striking changes in the expression and release patterns of key molecules that govern the neuroendocrine stress responses were observed. The presence of sustained stress was evident from enhanced activation of peripheral elements of the neuroendocrine stress response, i.e. increased basal plasma corticosterone concentrations, high adrenal weight and decreased body weight. Central regulatory elements of the neuroendocrine stress response were perturbed, including reduced expression of hypothalamic corticotropin-releasing hormone that, surprisingly, was accompanied by reduced glucocorticoid receptor expression. Thus, the effects of chronic sustained stress in the neonatal rat on the hypothalamic-pituitary-adrenal axis included substantial changes in the expression and activity of major regulators of this axis. Importantly, the changes induced by this chronic stress differed substantially from those related to acute or recurrent stress, providing a novel model for studying the long-term effects of chronic, early life stress on neuroendocrine functions throughout life.     

Comparison of the spatial distribution of seven types of neuroendocrine neurons in the rat paraventricular nucleus: Toward a global 3D model

The paraventricular nucleus of the hypothalamus (PVH) coordinates neuroendocrine, autonomic, and behavioral responses to help maintain energy and body water balance. The rat paraventricular nucleus has three major divisions: descending with axonal projections to somatomotor‐behavioral and autonomic circuitry, magnocellular neuroendocrine with projections directly to the posterior pituitary, and parvicellular neuroendocrine with projections to the median eminence for controlling anterior pituitary hormone secretion. The present work was undertaken to provide high‐resolution mapping of spatial relationships among the two magnocellular neuroendocrine and five parvicellular neuroendocrine neuron types throughout the nucleus. Double immunohistochemical labeling for two neuron types combined with retrograde labeling to identify neuroendocrine neurons positively was used in individual sections spaced 45 μm apart, along with a grid transfer method for reducing plane of section artifacts when comparing staining pattern data between animals. The results indicate that whereas each neuroendocrine neuron phenotype displays a unique distribution pattern, there is extensive partial overlap in a complex pattern between small “hot spots” with a relatively high density of a particular neuron type and few if any other phenotypes. In addition, the distribution of non‐neuroendocrine neurons staining with each of the markers (but not retrogradely labeled) was mapped and compared with each other and with the neuroendocrine neuron populations. This spatial organization raises important questions about the differential functional regulation of individual—and perhaps sets of—neuroendocrine motor neuron populations in the PVH by synaptic mechanisms and by less traditional mechanisms like dendritic neurotransmitter release and gap junctions within and between neuron types. J. Comp. Neurol. 516:423–441, 2009. © 2009 Wiley‐Liss, Inc.     

Peripheral corticotropin‐releasing factor (CRF) induces stimulation of gastric contractions in freely moving conscious rats: role of CRF receptor types 1 and 2

Background Peripheral corticotrophin‐releasing factor (CRF) plays an important role in stress‐induced alterations of gastrointestinal motility. CRF injected peripherally inhibits gastric emptying, but its effect on gastric contractions has not been clarified in freely moving conscious rats. Methods Intraluminal gastric pressure waves were measured in freely moving conscious non‐fasted rats using the perfused manometric method. We assessed the area under the manometric trace as the motor index (MI), and compared this result with those obtained 1 h before and after drug administration. Key Results Subcutaneous injection (sc) of CRF (15 μg kg^?1) increased the MI significantly. Pretreatment with intravenous astressin (100 μg kg^?1), a non‐selective CRF antagonist, blocked the sc CRF (15 μg kg^?1)‐induced response, but astressin₂‐B (200 μg kg^?1, sc), a selective CRF receptor type 2 (CRF₂) antagonist, enhanced the CRF‐induced increase in MI significantly. Meanwhile urocortin 2 (15 μg kg^?1, sc), a selective CRF₂ agonist, did not alter the basal MI, but it inhibited the sc CRF (15 μg kg^?1)‐induced stimulation of gastric contractions. The intraperitoneal injection of cortagine (30 μg kg^?1), a selective CRF receptor type 1 (CRF₁) agonist, mimicked the response induced by sc CRF. Conclusions & Inferences Peripheral CRF stimulates gastric contractions through CRF₁. CRF₂ activation inhibits the response induced by CRF, suggesting that CRF₂ may have a modulatory action to CRF₁ signaling in gastric motor activity.     

Corticotropin‐releasing factor‐2 activation prevents gentamicin‐induced oxidative stress in cells derived from the inner ear

Generation of reactive oxygen species (ROS) is a common denominator in many conditions leading to cell death in the cochlea, yet little is known of the cochlea's endogenous mechanisms involved in preventing oxidative stress and its consequences in the cochlea. We have recently described a corticotropin‐releasing factor (CRF) signaling system in the inner ear involved in susceptibility to noise‐induced hearing loss. We use biochemical and proteomics assays to define further the role of CRF signaling in the response of cochlear cells to aminoglycoside exposure. We demonstrate that activity via the CRF₂ class of receptors protects against aminoglycoside‐induced ROS production and activation of cell death pathways. This study suggests for the first time a role for CRF signaling in protecting the cochlea against oxidative stress, and our proteomics data suggest novel mechanisms beyond induction of free radical scavengers that are involved in its protective mechanisms. © 2010 Wiley‐Liss, Inc.     

Corticotropin-releasing factor, urocortin 1, and their receptors in the mouse spinal cord

Corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1) are involved in stress adaptation. CRF receptor 1 (CRF1) binds CRF and Ucn1 with similar high affinity, but CRF receptor 2 (CRF2) binds Ucn1 with higher affinity than CRF. We tested the hypothesis that in the spinal cord CRF and Ucn1 control peripheral components of the stress response, by assessing the distribution of CRF- and Ucn1-containing fibers, CRF1 and CRF2 mRNAs, and CRF receptor protein (CRFR) in the mouse spinal cord, by using immunofluorescence and in situ hybridization. CRF, Ucn1, and CRFR occurred throughout the spinal cord. CRF fibers predominated in laminae I, V-VII, and X of Rexed. Ucn1 fibers occurred mainly in laminae VII and X and occasionally in lamina IX. Both CRFR mRNAs occurred in all laminae except the superficial laminae of the dorsal horn, but they exhibited different distributions, CRF2 mRNA having a wider occurrence (laminae III-X) than CRF1 mRNA (laminae III-VIII). Double immunofluorescence indicated that CRF and Ucn1 fibers contacted CRFR-containing neurons, mainly in laminae VII and X. The strongest co-distribution of CRF1 and CRF2 mRNAs with CRF and Ucn1 fibers appeared in lamina VII. CRF2 mRNA predominated in lamina IX together with Ucn1, whereas CRF2 mRNA predominated in lamina X, where it had similar distributions with each ligand. In view of the lamina-specific and similar distributions of the two CRF receptor mRNAs with their ligands, we suggest that CRF1 and CRF2 are involved in peripheral stress adaptation processes, such as modulation of stress-induced analgesia and the mediation of visceral nociceptive information by CRF2.     

Bed nucleus of the stria terminalis: cytoarchitecture, immunohistochemistry, and projection to the parabrachial nucleus in the rat

The bed nucleus of the stria terminalis (BST) sends a dense projection to the parabrachial nucleus (PB) in the pons. The BST contains many different types of neuropeptidelike immunoreactive cells and fibers, each of which exhibits its own characteristic distribution within cytoarchitecturally distinct BST subnuclei. Corticotropin releasing factor (CRF)-, neurotensin (NT)-, somatostatin (SS)-, and enkephalin (ENK)-like immunoreactive (ir) neurons are particularly numerous within areas of the BST that project to the PB. In this study, we use the combined retrograde fluorescence-immunofluorescence method to determine whether neurons in the BST that project to the PB contain these immunoreactivities. After Fast Blue injections into PB, retrogradely labeled neurons were numerous throughout the lateral part of the BST, particularly in the dorsal lateral (DL) and posterior lateral subnuclei. Retrogradely labeled neurons were also present in the preoptic, ventral lateral, and supracapsular BST subnuclei and in the parastrial nucleus. Many of the CRF-ir, NT-ir, and SS-ir neurons in DL were retrogradely labeled. A few double-labeled cells of each type were also found in the posterior lateral, ventral lateral and supracapsular BST subnuclei ENK-ir neurons were never retrogradely labeled. Our results show that BST neurons that project to the PB stain for the same neuropeptides as those in the central nucleus of the amygdala (CeA) that project to the PB, demonstrating further the close anatomical relations between these two structures.     

Intrathecal urocortin I in the spinal cord as a murine model of stress hormone‐induced musculoskeletal and tactile hyperalgesia

Stress is antinociceptive in some models of pain, but enhances musculoskeletal nociceptive responses in mice and muscle pain in patients with fibromyalgia syndrome. To test the hypothesis that urocortins are stress hormones that are sufficient to enhance tactile and musculoskeletal hyperalgesia, von Frey fibre sensitivity and grip force after injection of corticotropin‐releasing factor (CRF), urocortin I and urocortin II were measured in mice. Urocortin I (a CRF1 and CRF2 receptor ligand) produced hyperalgesia in both assays when injected intrathecally (i.t.) but not intracerebroventricularly, and only at a large dose when injected peripherally, suggesting a spinal action. Morphine inhibited urocortin I‐induced changes in nociceptive responses in a dose‐related fashion, confirming that changes in behaviour reflect hyperalgesia rather than weakness. No tolerance developed to the effect of urocortin I (i.t.) when injected repeatedly, consistent with a potential to enhance pain chronically. Tactile hyperalgesia was inhibited by NBI‐35965, a CRF1 receptor antagonist, but not astressin 2B, a CRF2 receptor antagonist. However, while urocortin I‐induced decreases in grip force were not observed when co‐administered i.t. with either NBI‐35965 or astressin 2B, they were even more sensitive to inhibition by astressin, a non‐selective CRF receptor antagonist. Together these data indicate that urocortin I acts at CRF receptors in the mouse spinal cord to elicit a reproducible and persistent tactile (von Frey) and musculoskeletal (grip force) hyperalgesia. Urocortin I‐induced hyperalgesia may serve as a screen for drugs that alleviate painful conditions that are exacerbated by stress.     

The role of the bed nucleus of the stria terminalis in stress-induced inhibition of pulsatile luteinising hormone secretion in the female rat

The bed nucleus of the stria terminalis (BNST) occupies a central position in the neural circuitry regulating the hypothalamic-pituitary-adrenocortical axis response to stress. The potential role of the BNST in stress-induced suppression of the gondotrophin-releasing hormone (GnRH) pulse generator, the central regulator of the reproductive system, was assessed by examining the effects of micro-infusion of corticotrophin-releasing factor (CRF) or its antagonist into the BNST on pulsatile luteinising hormone (LH) secretion or stress-induced inhibition of LH pulses, respectively. Ovariectomised oestrogen-treated rats were implanted chronically with bilateral cannulae in the dorsolateral BNST and i.v. catheters. CRF (25, 50 or 100 pmol in 200 nl of artificial cerebrospinal fluid) administered bilaterally into the BNST resulted in a dose-dependent decrease in LH pulse frequency, and induced Fos expression in glutamic acid decarboxylase immunostained neurones in the medial preoptic area. These results suggest that the activation of hypothalamic GABAergic neurones in response to intra-BNST administration of CRF may be involved in the suppression of LH pulses. Furthermore, administration of CRF antagonist (280 pmol astressin-B, three times at 20-min intervals) into the BNST effectively blocked the suppression of pulsatile LH secretion in response to restraint (1 h) but not hypoglycaemic (0.25 U insulin/kg, i.v.) stress. These data suggest that CRF innervation of the dorsolateral BNST plays a key, but differential, role in stress-induced suppression of the GnRH pulse generator.     

Differential stress‐induced alterations of colonic corticotropin‐releasing factor receptors in the Wistar Kyoto rat

Background A growing body of data implicates increased life stresses with the initiation, persistence and severity of symptoms associated with functional gut disorders such as irritable bowel syndrome (IBS). Activation of central and peripheral corticotropin‐releasing factor (CRF) receptors is key to stress‐induced changes in gastrointestinal (GI) function. Methods This study utilised immunofluorescent and Western blotting techniques to investigate colonic expression of CRF receptors in stress‐sensitive Wistar Kyoto (WKY) and control Sprague Dawley (SD) rats. Key Results No intra‐strain differences were observed in the numbers of colonic CRFR1 and CRFR2 positive cells. Protein expression of functional CRFR1 was found to be comparable in control proximal and distal colon samples. Sham levels of CRFR1 were also similar in the proximal colon but significantly higher in WKY distal colons (SD: 0.38 ± 0.14, WKY: 2.06 ± 0.52, P < 0.01). Control levels of functional CRFR2 were similar between strains but sham WKYs samples had increased CRFR2 in both the proximal (SD: 0.88 ± 0.21, WKY: 1.8 ± 0.18, P < 0.001) and distal (SD: 0.18 ± 0.08, WKY: 0.94 ± 0.32, P < 0.05) regions. Exposure to open field (OF) and colorectal distension (CRD) stressors induced decreased protein expression of CRFR1 in SD proximal colons, an effect that was blunted in WKYs. CRD stimulated decreased expression of CRFR2 in WKY rats alone. Distally, CRFR1 is decreased in WKY rats following CRD but not OF stress without any apparent changes in SD rats. Conclusions & Inferences This study demonstrates that psychological and physical stressors alter colonic CRF receptor expression and further support a role for local colonic CRF signalling in stress‐induced changes in GI function.     

The role of stress in the onset of depressive disorders

Background: We conducted the present study to evaluate the impact of stressful events on the onset of depressive disorders in a Spanish clinical sample, compared to a control group matched for age, sex, civil status and social class. We compared our results with those of other studies carried out with samples that were both clinically and culturally similar to ours. Method: Fifty depressed patients that were diagnosed with a depressive episode in the 6 months prior to the interview and 50 healthy controls were included in the study. Both groups were compared on the “Life Events and Difficulties Schedule” (LEDS). Results: Of the depressive patients, 68 % compared to only 18 % of the control individuals experienced at least one provoking agent in the 12 months prior to the onset of the symptoms. The risk of developing a depressive disorder was 9.7 % greater in subjects exposed to such provoking agents. Chronic difficulties are equally important to the genesis of depressive disorders as severe life events. No significant differences were seen between the two diagnostic subgroups of depressed patients in the accumulation of severe events, major difficulties or provoking agents. Conclusion: The results support the view that stress is a major factor in the aetiology of depressive disorders. The amount of stress suffered by the patients, however, was less than that found in our healthy sample. Important issues about the model of interaction between stress and depression are discussed. Accepted: 29 July 2002 Correspondence to L. Rojo     

Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults

Catecholamine-containing projections from the medulla have been implicated in the mediation of activational responses of the paraventricular nucleus of the hypothalamus (PVH) provoked by moderate doses of interleukin-1 (IL-1). To test the generality of this mechanism, rats bearing unilateral transections of aminergic projections were challenged with intravenous IL-1 (2 microg/kg), bacterial lipopolysaccharide (LPS; 0.1, 2.0, or 100 microg/kg), or saline and perfused 3 hours later; their brains were then prepared for quantitative analysis of Fos induction and relative levels of corticotropin-releasing factor (CRF) mRNA. LPS provoked a robust and dose-related increase in Fos expression within the PVH on the intact side of the brain at all doses tested; the response to IL-1 approximated that to the lowest LPS dose. On the lesioned side, Fos induction was significantly reduced at all dosage levels but was eliminated only at the lowest dosage. The percentage reduction was greatest (75%) in IL-1-challenged rats and was progressively less in animals treated with increasing LPS doses (67, 59, and 46%, respectively). Specificity of aminergic involvement was tested by using intra-PVH administration of the axonally transported catecholamine immunotoxin, antiDBH-saporin. This treatment abolished IL-1-induced elevations of Fos-ir and CRF mRNA in the PVH but left intact comparable responses to restraint stress. These data support a specific involvement of ascending catecholaminergic projections in mediating PVH responses to IL-1 and LPS. Residual Fos induction seen in lesioned animals in response to higher doses of LPS provides a basis for probing additional circuits that may be recruited in a hierarchical manner in response to more strenuous or complex immune insults.     

CRF1 and CRF2 receptors in the bed nucleus of stria terminalis differently modulate the baroreflex function in unanesthetized rats

The baroreflex is an important blood pressure regulating mechanism. The bed nucleus of stria terminalis (BNST) modulates the baroreflex function. However, the local BNST neurochemical mechanisms involved in control of baroreflex responses are not completely understood. Therefore, in this study, we investigated the involvement of corticotropin‐releasing factor (CRF) receptors within the BNST in baroreflex control of heart rate in unanesthetized rats. For this, we evaluated effects of bilateral microinjection into the BNST of either the selective CRF₁ receptor antagonist CP376395 (5 nmol/100 nL) or the selective CRF₂ receptor antagonist antisauvagine‐30 (5 nmol/100 nL) in bradycardiac response evoked by blood pressure increases caused by intravenous infusion of phenylephrine as well as tachycardiac response to blood pressure decrease caused by intravenous infusion of sodium nitroprusside. Bilateral microinjection of CP376395 into the BNST decreased the baroreflex bradycardiac response without affecting the reflex tachycardia. Conversely, BNST treatment with antisauvagine‐30 decreased heart rate response during blood pressure drop without affecting the reflex bradycardia. Overall, these findings provide evidence of an involvement of CRF neurotransmission within the BNST in baroreflex activity. Nevertheless, data indicate that local CRF₁ and CRF₂ receptors differently modulate the baroreflex control of heart rate.     

Sex differences in the ontogeny of CRF receptors during adolescent development in the dorsal raphe nucleus and ventral tegmental area

Interactions between corticotropin‐releasing factor (CRF) and monoaminergic systems originating from the dorsal raphe nucleus (DR) and ventral tegmental area (VTA) have been implicated in the etiology and pathophysiology of several stress‐related neuropsychiatric disorders such as depression and substance abuse. Sub‐regions within the DR and VTA give rise to specific projections that have unique roles in limbic‐ and reward‐related behaviors. Given that these disorders typically emerge during adolescence, it is surprising that few studies have examined the age‐, sex‐, and region‐dependent expression of CRF receptors throughout multiple stages of adolescence in these stress‐relevant circuits. To determine the ontogeny of CRF receptors during adolescent development, three regions of the DR (dorsal, caudal, and ventrolateral parts) and the posterior VTA were microdissected from Sprague‐Dawley male and female rats on postnatal day (P) 25, P35, P42, P56, and P90. Tissue was processed and analyzed with qRT‐PCR to measure CRF₁ and CRF₂ receptors. The serotonin and catecholamine enzymes in the DR and VTA, tryptophan hydroxylase 2 (TPH2) and tyrosine hydroxylase, respectively, were also analyzed for maturational differences. This study identified that CRF₁ receptors are lower in males than females within the dorsal, ventrolateral region of the DR (DRVL), which is involved in anxiety‐, stress‐, and panic‐related responses. Females had higher CRF₂ receptors compared to males in the DRVL only. Levels of TPH2 mRNA in the DRVL were overproduced transiently in females before declining into adulthood. These fundamental studies suggest that sex differences in CRF receptors should be considered when examining stress‐related neuropsychiatric disorders and their treatment. Synapse 70:125–132, 2016. © 2016 Wiley Periodicals, Inc.     

Central somatostatin receptor 1 activation reverses acute stress‐related alterations of gastric and colonic motor function in mice

Background Corticotropin‐releasing factor (CRF) signaling induced by stress is well established to delay gastric emptying (GE) and stimulate colonic functions. The somatostatin receptor (sst_1–5) agonist, ODT8‐SST acts in the brain to inhibit stress‐induced adrenocorticotropic hormone and epinephrine secretion. We investigated whether ODT8‐SST acts in the brain to influence stress‐related alterations of gastric and colonic motor function and sst receptor subtype(s) involved. Methods Peptides were injected intracerebroventricularly (i.c.v.) under short isoflurane anesthesia and GE, fecal pellet output (FPO) and distal colonic motility monitored in conscious mice. Key Results The stress of acute anesthesia/vehicle i.c.v. injection reduced GE by 67% and increased defecation by 99% compared to non‐injected controls. Both responses were abolished by ODT8‐SST (1 μg = 0.75 nmol) or sst₁ agonist (0.65–1.95 nmol). The sst₁ agonist (1.95 nmol) also prevented the abdominal surgery‐induced delayed GE. Octreotide (sst₂ > sst₅ > sst₃) and the sst₂ or sst₄ agonists (1 μg = 0.78 or 0.70 nmol, respectively) injected i.c.v. did not influence FPO while i.c.v. somatostatin‐28 mimicked ODT8‐SST’s effect. The ODT8‐SST‐induced increased food intake was inhibited by i.c.v. sst₂ antagonist while the reduced FPO was unchanged. ODT8‐SST i.c.v. reduced distal colonic motility in semi‐restrained mice compared with vehicle and blocked water avoidance‐ and i.c.v. CRF (0.5 μg = 0.09 nmol)‐induced stimulated FPO while a similar colonic secretomotor response to i.p. 5‐hydroxytryptophane (10 mg kg^?1 = 36.4 μmol kg^?1) was unaltered. Conclusions & Inferences ODT8‐SST counteracts stress/i.c.v. CRF‐related stimulation of colonic motor function and delayed GE which can be reproduced mainly by activation of sst₁ receptors. These data opens new insight to brain somatostatinergic signaling pathways interfering with brain circuitries involved in gut motor responses to acute stress.     

Differences in the determinants of posttraumatic stress disorder and depression after a mass traumatic event

Background: Hurricane Ike struck the Galveston Bay area of Texas on September 13, 2008, leaving substantial destruction and a number of deaths in its wake. We assessed differences in the determinants of posttraumatic stress disorder (PTSD) and depression after this event, including the particular hurricane experiences, including postevent nontraumatic stressors, that were associated with these pathologies. Methods: 658 adults who had been living in Galveston and Chambers counties, TX in the month before Hurricane Ike were interviewed 2–5 months after the hurricane. We collected information on experiences during and after Hurricane Ike, PTSD and depressive symptoms in the month before the interview, and socio‐demographic characteristics. Results: The prevalence of past month hurricane‐related PTSD and depression was 6.1 and 4.9%, respectively. Hurricane experiences, but not socio‐demographic characteristics, were associated with Ike‐related PTSD. By contrast, lower education and household income, and more lifetime stressors were associated with depression, as were hurricane exposures and hurricane‐related stressors. When looking at specific hurricane‐related stressors, loss or damage of sentimental possessions was associated with both PTSD and depression; however, health problems related to Ike were associated only with PTSD, whereas financial loss as a result of the hurricane was associated only with depression. Conclusions: PTSD is indeed a disorder of event exposure, whereas risk of depression is more clearly driven by personal vulnerability and exposure to stressors. The role of nontraumatic stressors in shaping risk of both pathologies suggests that alleviating stressors after disasters has clear potential to mitigate the psychological sequelae of these events. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.