Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The characterization of corticotropin releasing factor (CRF) and, more recently, the discovery of additional CRF-related ligands, urocortin 1, urocortin 2 and urocortin 3, the cloning of two distinct CRF receptor subtypes, 1 (CRF(1)) and 2 (CRF(2)), and the development of selective CRF receptor antagonists provided new insight to unravel the mechanisms of stress. Activation of brain CRF(1) receptor signaling pathways is implicated in stress-related endocrine response and the development of anxiety-like behaviors. 2. Compelling evidence in rodents showed also that both central and peripheral injection of CRF and urocortin 1 mimic acute stress-induced colonic response (stimulation of motility, transit, defecation, mucus and watery secretion, increased ionic permeability and occurrence of diarrhea) in rodents. Central CRF enhances colorectal distention-induced visceral pain in rats. Peripheral CRF reduced pain threshold to colonic distention and increased colonic motility in humans. 3. Nonselective CRF(1)/CRF(2) antagonists and selective CRF(1) antagonists inhibit exogenous (central or peripheral) CRF- and acute stress-induced activation of colonic myenteric neurons, stimulation of colonic motor function and visceral hyperalgesia while selective CRF(2) antagonists have no effect. None of the CRF antagonists influence basal or postprandial colonic function in nonstressed animals. 4. These findings implicate CRF(1) receptors in stress-related stimulation of colonic function and hypersensitivity to colorectal distention. Targeting CRF(1)-dependent pathways may have potential benefit against stress or anxiety-/depression-related functional bowel disorders.
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PMID:CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome. 1510 Jan 65

The stress-related neuropeptide corticotropin-releasing factor (CRF) and the serotonin system are both critically involved in the pathophysiology of mental disorders, including anxiety and depression. To understand the potential link between them, we investigated the impact of CRF on 5-HT functions in pyramidal neurons of the prefrontal cortex (PFC), a brain region that is crucial for the control of emotion and cognition. One prominent function of serotonin in PFC is to regulate GABAergic inhibitory transmission, as indicated by a 5-HT-induced large, desensitizing (approximately 4 min) enhancement of the amplitude and frequency of spontaneous IPSCs (sIPSCs). In PFC slices exposed to CRF treatment, the regulation of sIPSCs by 5-HT was significantly prolonged (8-10 min), and this effect of CRF was blocked by treatment with the competitive CRF receptor antagonist alpha-helical CRF9-41 and with the CRF-R1-specific antagonist astressin. Inhibiting phospholipase C or protein kinase C (PKC) abolished the prolongation by CRF of the effects of 5-HT on sIPSCs. In PFC slices prepared from animals previously exposed to acute stress (forced swim or elevated platform), the regulation of sIPSCs by 5-HT was significantly prolonged, mimicking the effect of CRF treatment. The stress-induced prolongation of the effects of 5-HT on sIPSCs was diminished by alpha-helical CRF9-41 treatment, mimicked by direct activation of PKC, and reversed by short-term treatment with drugs that have anxiolytic efficacy. These results show that in response to stressful stimuli, CRF alters the serotonergic regulation of GABA transmission through a mechanism that is dependent on PKC. The interaction between CRF and 5-HT may play an important role in psychiatric disorders, in which both are highly implicated.
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PMID:Corticotropin-releasing factor and acute stress prolongs serotonergic regulation of GABA transmission in prefrontal cortical pyramidal neurons. 1516 92

Nightmares can be defined as very disturbing dreams, the events or emotions of which cause the dreamer to wake up. In contrast, unpleasant dreams can be defined in terms of a negative emotional rating of a dream, irrespective of whether or not the emotions or events of the dream woke the dreamer. This study addresses whether frequency of unpleasant dreams is a better index of low well-being than is frequency of nightmares. A total of 147 participants reported their nightmare frequency retrospectively and then kept a log of all dreams, including nightmares, for 2 weeks, and rated each dream for pleasantness/unpleasantness. Anxiety, depression, neuroticism, and acute stress were found to be associated with nightmare distress (ND) (the trait-like general level of distress in waking-life caused by having nightmares) and prospective frequency of unpleasant dreams, and less so with the mean emotional tone of all dreams, or retrospective or prospective nightmare frequency. Correlations between low well-being and retrospective nightmare frequency became insignificant when trait ND was controlled for, but correlations with prospective unpleasant dream frequency were maintained. The reporting of nightmares may thus be confounded and modulated by trait ND: such confounding does not occur for the reporting of unpleasant dreams in general. Thus there may be attributional components to deciding that one has been awoken by a dream, which can affect estimated nightmare frequency and its relationship with well-being. Underestimation of nightmare frequency by the retrospective questionnaire compared with logs was found to be a function of mean dream unpleasantness and ND.
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PMID:The relationship of nightmare frequency and nightmare distress to well-being. 1517 92

The implantable automatic defibrillator has completely changed the prognosis of potentially fatal ventricular arrhythmias by the delivery of an electric shock in the event of ventricular tachycardia or fibrillation. This vital device is sometimes poorly accepted from the psychological point of view by patients having been traumatised by experiences of sudden death from which they have been rescuscitated. Anxiety and depression are common and they have an important effect on the quality of life. The unpredictable occurrence of painful, multiple and uncontrollable electrical shocks may induce a state of acute stress with stunning, the resemblance of which to the model of learned helplessness described experimentally in the animal by Seligman, is discussed. The authors report the case of a 20 year old man whose automatic defibrillator was activated twenty times in one night. His state of stress and impotence was such that he lay prostate in his bed. Suicide seemed to be the only possible way of escaping from the electrical shocks of the device which was perceived as being dangerous. The management of this condition is not standardised but it requires the collaboration of the cardiac rhythmological and psychiatric teams. Medication with antidepressant drugs alone is not sufficient. The regulation of the sensitivity of the defibrillator gives the patient a feeling of mastering the situation: submission is not total! Research along this line should improve the patients' acceptation of the device and their quality of life.
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PMID:[Psychiatric complication of an implanted automatic defibrillator]. 1524 53

The authors assessed the psychological, neuropsychological, and electrocortical effects of human exposure to mixed colonies of toxigenic molds. Patients (N = 182) with confirmed mold-exposure history completed clinical interviews, a symptom checklist (SCL-90-R), limited neuropsychological testing, quantitative electroencephalogram (QEEG) with neurometric analysis, and measures of mold exposure. Patients reported high levels of physical, cognitive, and emotional symptoms. Ratings on the SCL-90-R were "moderate" to "severe," with a factor reflecting situational depression accounting for most of the variance. Most of the patients were found to suffer from acute stress, adjustment disorder, or post-traumatic stress. Differential diagnosis confirmed an etiology of a combination of external stressors, along with organic metabolically based dysregulation of emotions and decreased cognitive functioning as a result of toxic or metabolic encephalopathy. Measures of toxic mold exposure predicted QEEG measures and neuropsychological test performance. QEEG results included narrowed frequency bands and increased power in the alpha and theta bands in the frontal areas of the cortex. These findings indicated a hypoactivation of the frontal cortex, possibly due to brainstem involvement and insufficient excitatory input from the reticular activating system. Neuropsychological testing revealed impairments similar to mild traumatic brain injury. In comparison with premorbid estimates of intelligence, findings of impaired functioning on multiple cognitive tasks predominated. A dose-response relationship between measures of mold exposure and abnormal neuropsychological test results and QEEG measures suggested that toxic mold causes significant problems in exposed individuals. Study limitations included lack of a comparison group, patient selection bias, and incomplete data sets that did not allow for comparisons among variables.
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PMID:Psychological, neuropsychological, and electrocortical effects of mixed mold exposure. 1525 24

Depressive symptoms in the non-clinical range have been linked to increased health risks. Recent theorizing raises the possibility that heightened physiologic responses to acute stress and/or slowed stress recovery in individuals with depressive symptoms may contribute to increased risk. We investigated stress-induced catecholamine responses and recovery patterns using a modified version of the Trier Social Stress Test (15 min) with a sample of 52 healthy women and compared subgroups with high normal versus low scores on the Beck Depression Inventory (BDI, median split) to 29 women randomly assigned to a non-stressed control group. The BDI-high normal and BDI-low groups showed similar acute increases in epinephrine immediately post stressor, but only the BDI-high normal group remained significantly elevated above control group levels during the recovery period. No differences were found in norepinephrine responses. Elevations in BDI scores within the normal range may selectively predict slower physiological recovery following acute stress.
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PMID:Higher Beck depression scores predict delayed epinephrine recovery after acute psychological stress independent of baseline levels of stress and mood. 1529 85

The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.
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PMID:Cytokines: abnormalities in major depression and implications for pharmacological treatment. 1530 43

The direct hippocampal to prefrontal cortex pathway and its changes in synaptic plasticity is a useful framework for investigating the functional operations of hippocampal-prefrontal cortex communication in cognitive functions. Synapses on this pathway are modifiable and synaptic strength can be turned up or down depending on specific patterns of activity in the pathway. The objective of this review will be to summarize the different studies carried out on this topic including very recent data and to underline the importance of animal models for the development of new and effective medications in psychiatric diseases. We have shown that long-term potentiation (LTP) of hippocampal-prefrontal synapses is driven by the level of mesocortical dopaminergic (DA) activity and more recently that stress is also an environmental determinant of LTP at these cortical synapses. Stimulation of the ventral tegmental area at a frequency known to evoke DA overflow in the prefrontal cortex produces a long-lasting enhancement of the magnitude of hippocampal-prefrontal cortex LTP whereas a depletion of cortical DA levels generates a dramatic decrease in this LTP. Moreover, hippocampal stimulation induces a transient but significant increase in DA release in the prefrontal cortex and an optimal level of D1 receptor activation is essential for LTP expression. We recently investigated the impact of stress on hippocampal-prefrontal LTP and demonstrated that exposure to an acute stress causes a remarkable and long-lasting inhibition of LTP. Furthermore, we demonstrated that tianeptine, an antidepressant which has a unique mode of action, and clozapine an atypical antipsychotic when administered at doses normally used in human testing are able to reverse the impairment in LTP. Stressful life events have a substantial causal association with psychiatric disorders like schizophrenia and depression and recent imaging studies have shown an important role of the limbic-cortical circuit in the pathophysiology of these illnesses. Therefore, we proposed that agents capable of reversing the impairment of plasticity at hippocampal to prefrontal cortex synapses have the potential of becoming new therapeutic classes of antidepressant or antipsychotic drugs.
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PMID:Plasticity at hippocampal to prefrontal cortex synapses is impaired by loss of dopamine and stress: importance for psychiatric diseases. 1532 62

Wistar-Kyoto (WKY) rats exhibit hyperresponsive neuroendocrine and behavioral responses to stress that exceed normal controls and are especially prone to develop stress-induced depressive disorder. Pharmacological studies indicate altered serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems functioning in WKY rats, yet no attempt has been made to provide a comprehensive assessment of the neurochemical profile for WKY rats as compared to the outbred progenitor controls, Wistar rats. To this end, male, WKY and Wistar rats (N=6/group) were exposed to an acute forced-swim stress or were left untreated as controls. The prefrontal cortex (PFCtx), striatum, nucleus accumbens (NAS), and amygdala were assayed for levels of NE, DA and 5-HT, as well as major metabolites, by high-pressure liquid chromatography (HPLC) with electrochemical detection. In a separate experiment, designed to assess baseline and stress-induced neuroendocrine activation, male, Wistar and WKY rats (N=6/group) were exposed to an acute forced-swim stress of 15 min or were left untreated as controls. Animals were killed immediately after the test (T=0), 30 min after the test (T=30) or 60 min after the test (T=60), and control animals were killed immediately after weighing. After decapitation, trunk blood was collected and plasma was isolated by centrifugation and analyzed for corticosterone by immunoassay. The neurochemical results demonstrate distinct patterns of baseline and stress-induced monoamine turnover in WKY rats, including alterations to DA and 5-HT turnovers in prefrontal cortex and nucleus accumbens, two critical brain areas implicated in anxiety, depression and drug reward. The neuroendocrine results indicate that WKY rats exhibited a sustained corticosterone response to acute stress, as compared to Wistar controls. Overall, these data are predicted to be useful for understanding the anxiety- and depressive-like behavioral phenotype exhibited by these animals and for increased understanding of the role genetic background in altering neurochemical function.
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PMID:A distinct neurochemical profile in WKY rats at baseline and in response to acute stress: implications for animal models of anxiety and depression. 1534 69

Many clinic investigations support the relation between coronary heart disease (CAD) and psychosocial factors (PFs) and how these two entities influence each other. On one hand, FPs like depression, anxiety, social isolation, stress and some types of personality, contribute significantly to the pathogenesis and expression of CAD. Pathophysiological mechanisms underly in this interrelation, can be divided between FPs conditions that contribute to a higher frequency of adverse health behaviors (eg. smoking) or directly increasing the platelets and neuroendocrine activity. In this review there is information relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. Recent data also indicate that the foregoing effects are in part a result of the endothelial dysfunction and injury induced by acute stress. The complex interactions among vascular endothelium, platelets, serotonin and blood components are one of the most exciting research areas today. The importance of maximizing the efficacy of psychological and psychopharmacology interventions is in part because of the knowledge that psychosocial stresses tend to cluster together and when this takes place, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia. Thus, to know about these mechanisms, helps to widen the view and use therapeutic strategies that go beyond symptomatic effects and commit us to an interdisciplinary work.
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PMID:[Stress, anxiety and cardiovascular disease: an interdisciplinary approach]. 1550 91


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