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)

Overactivity of the hypothalamus-pituitary-adrenal axis (HPAA) has been observed in the presence of acute stress and, under chronic conditions, in disorders such as depression and anorexia nervosa as well as in cardiovascular and metabolic disorders. However, there may be other stress-related disorders (fatigue, pain, etc) that seem to be associated with mild hypocortisolism. This suggests that two major subtypes of the HPAA response to stress need to be discriminated. In this study, we investigated 76 subjects with and without hypocortisolism, respectively, over a 1-year period. Surprisingly, hypocortisolemic subjects had a lower allostatic load but they scored higher on measures of depression, perceived stress, and physical complaints. We propose a protective role of the hypocortisolemic stress response on cardiovascular and metabolic disorders, particularly in the elderly.
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PMID:Allostatic load, perceived stress, and health: a prospective study in two age groups. 1567 92

Depression is one of the most common human illnesses and is of immense clinical and economic significance. Knowledge of the neuro-psychology, -biology and -pharmacology of depression is limited, as is the efficacy of antidepressant treatment. In terms of depression aetiology, whilst the evidence for causal mechanisms is sparse, some genomic and environmental factors associated with increased vulnerability have been identified. With regards to the latter, the environments in which human infants and children develop are fundamental to how they develop, and parental loss, emotional and physical neglect, and abuse have been shown to be associated with: traits of depression, traits of predisposition to depression triggered by subsequent life events, and associated physiological abnormalities, across the life span. Studies of postnatal environmental manipulations in rodents and primates can potentially yield evidence that abnormal early-life experience leading to dysfunction of the neurobiology, physiology and behaviour of emotion is a general mammalian characteristic, and therefore, that this approach can be used to develop animal models for depression research, with aetiological, face, construct and predictive validity. The establishment of models with such validity, if at all achievable, will require a sophisticated combination of (1) appropriate postnatal manipulations that induce acute stress responses in the infant brain which in turn lead to long-term neurobiological consequences, and (2) appropriate behavioural and physiological assays to identify and quantify any depression-like phenotypes resulting from these long-term neurobiological phenotypes. Here, we review some of the evidence-positive and negative-that neglect-like environments in rat pups and monkey infants lead to long-term, depression-like behavioural traits of reduced motivation for reward and impaired coping with adversity, and to altered activity in relevant physiological homeostatic systems.
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PMID:Long-term effects of early-life environmental manipulations in rodents and primates: Potential animal models in depression research. 1592 98

Of all the psychological complications that an individual is likely to present with when confronted with an exceptional event, the Post-Traumatic Stress Disorder is characterized by being progressive, frequent, invalidating, strongly associated with comorbidity, and having the tendency to become chronic if it is not detected clinically. By definition, it is threatening and produces an intense fear reaction. The traumatic event is a situation of extreme stress, not only capable of altering the physical and psychological homeostasis of the individual, but is also recognized as determinant in the aetiopathology of complications. The intensity of this distress can be identified clinically and physiologically, and is currently considered as an important risk factor for the development of PTSD later on, together with other pre-, peri- and post-traumatic factors. In fact, the most studied field is the therapeutic approach, in particular drug treatment, of the fully-constituted disorder, although this actually represents tertiary prevention. Even though primary prevention seems to concern Medicine very little, any prospect of performing secondary prevention should begin by rapid identification of the risk or vulnerability factors and should allow a population at risk from developing complications to be defined. Its potential therapeutic impact brings together psychotherapeutic and drug treatment, since it is only this combination that seems able to allow the most favourable clinical outcome to be achieved for an individual, who is confronted by an out-of-the-ordinary event. The aims of secondary prevention strategies are, for example, to reduce the incidence of acute PTSD in patients seen following the event. The benefits for the individual and for the society can easily be measured in terms of the consequences on his/her social, professional and family life, or in terms of cost. The usefulness of this prevention can also be measured by the possible ways that other conditions, comorbid to PTSD, are controlled, such as anxiety disorders, depression and substance abuse, for example. Secondary prevention strategies may also be aimed at determining the therapeutic impact, by preventing or moderating the appearance of an acute stress, or even by contributing in avoiding the onset of chronic PTSD. Psychopharmacology of the immediate and post-immediate disorders, however, remains a field which has been studied very little. Reduction or control of the high, prolonged level of hyperarousal phenomena or hypersensitization of the hypothalamo-pituitary axis, would contribute to the comfort of the individual, and would participate in the prevention of PTSD. Based on current knowledge of the neurobiology of trauma, we look into the existing and potential pharmacological possibilities. Even though benzodiazepines tend to have an important role, knowledge of other drugs and therapeutic groups is rapidly increasing. In this review, we will see that the efficacy of anti-adrenergic drugs and certain other anxiolytics is now well-documented, this opening the door to their use in the future. Other drug groups offer interesting, well-proven approaches, such as serotoninergic drugs, CRF or NPY antagonists, NMDA antagonists, anticonvulsants or other GABAergic agents. In view of this disorder, which represents a true public health problem, we consider that it is now possible to widen the horizons of our drug therapy, in combination with any necessary psychotherapeutic treatment, to reach the heart of the traumatic event, that often upsets the victims, both by the psychological suffering it induces, and the loss of his/her social, family and professional references and support structures.
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PMID:[From the biology of trauma to secondary preventive pharmalogical measures for post-traumatic stress disorders]. 1595 48

The aim of this study was to evaluate the efficacy of agomelatine (S 20098) to accelerate reversal of the neuroendocrinological, behavioural and cyclical changes seen in a transgenic mouse model of the neuroendocrine characteristics of depression. The effects of agomelatine were assessed in transgenic mice with low glucocorticoid receptor (GR) function, after acute stress or induced phase shift, and compared to desipramine and melatonin. Mice were injected 2 h before the onset of the dark period with agomelatine (10 mg/kg, i.p.), desipramine (10 mg/kg, i.p.), melatonin (10 mg/kg, i.p.) or vehicle (hydroxy-ethyl-cellulose (HEC) 1%) each day for 21 to 42 days. Agomelatine was effective in reversing the transgenic mouse behavioural changes noted in the Porsolt forced swim test as well as in the elevated plus maze. Both the number of open arm entries and the total time spent in open arms of the elevated plus maze is greatly increased in transgenic mice. The mean time spent in open arms is exquisitely sensitive to reversal by agomelatine and desipramine. Agomelatine also markedly accelerated readjustment of circadian cycles of temperature and activity following an induced phase shift. This action of agomelatine was superior to that of melatonin while desipramine was without effect. The accelerating effect of agomelatine was particularly notable if treatment was started 3 weeks prior to the induced phase shift. Agomelatine treatment did not cause any major change in corticosterone or adrenocorticotropic hormone (ACTH) concentrations nor in vasopressin (AVP), corticotropin-releasing hormone (CRH), GR and mineralocorticoid receptor (MR) mRNAs levels, which make it unlikely that the mechanism of agomelatine action is related to hypothalamic-pituitary-adrenocortical (HPA) axis changes. The present study shows that agomelatine displays some characteristics of antidepressant drug action in the transgenic mouse model, effects that could be partially related to its chronobiotic properties.
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PMID:Antidepressant action of agomelatine (S 20098) in a transgenic mouse model. 1600 35

Daily restraint for 3 weeks was shown to atrophy dendrites of hippocampal pyramidal neurons in rats. Brain-derived neurotrophic factor (BDNF), which maintains neuronal survival and morphology, has been shown to decrease in response to acute stress. Plasma glucocorticoid (GC) and serotonergic projections from the raphe nuclei play major roles in reducing BDNF synthesis in the hippocampus. We investigated BDNF mRNA levels there, together with plasma GC levels, GC receptors in the hippocampus/hypothalamus and 5-HT synthesizing enzyme, tryptophan hydroxylase in the raphe nuclei, in animals chronically stressed for 1-3 weeks, using in situ hybridization and immunohistochemistry. In these animals, BDNF mRNA levels were significantly decreased in the hippocampus after 6 h of restraint, but the ability of restraint to reduce BDNF synthesis seemed less robust than that seen in acute stress models. HPA axis response to stress in these animals assessed by plasma GC levels was delayed and sustained, and the GC receptor in the paraventricular hypothalamic nucleus was increased at 1 week. Tryptophan hydroxylase immunoreactivity was increased in the median raphe nucleus at 2-3 weeks. Repetitive stress-induced reduction of BDNF may partly contribute to the neuronal atrophy/death and reduction of hippocampal volume observed both in animals and humans suffering chronic stress and/or depression.
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PMID:Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. 1602 25

The identification of the various elements of the Corticotropin Releasing Factor (CRF) system including the characterisation of four mammalian CRF-related peptides, the cloning of two CRF receptor subtypes 1 and 2 (CRF1; CRF2) and the development of selective CRF1 receptor antagonists has allowed investigators to establish an important role for the CRF signalling pathways in coordinating the physiological and behavioural components of the stress response. In particular, compelling preclinical evidence showed that both central and peripheral injection of CRF mimicked stress-induced stimulation of colonic motility, transit, defaecation, and occurrence of diarrhoea along with degranulation of mast cells, and increased secretion of prostaglandin E2, mucus, and ionic permeability. Central CRF also increased abdominal pain from colorectal distention in rats and peripheral CRF reduced pain threshold to colonic distention and increased colonic motility in humans. Non-selective CRF antagonists for receptors 1 and 2 and selective CRF, antagonists inhibit exogenous (central or peripheral) CRF, and acute stress-induced stimulation of colonic motor and secretory function and visceral hyperalgesia. CRF1 receptors mediate stress-related anxiogenic and depression-like behaviours in rodents and CRF, antagonist reduced depression in a phase II clinical trial. These findings lend support to the hypothesis that hyperactivation of CRF1 receptors may contribute to the co-morbidity of anxiety and depression and irritable bowel syndrome. Targeting these pathways with selective CRF1 antagonists may be a novel therapeutic venue for diarrhoea-predominant IBS patients.
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PMID:Role of corticotropin releasing factor receptor subtype 1 in stress-related functional colonic alterations: implications in irritable bowel syndrome. 1614 97

The brain noradrenergic system is activated by acute stress. The post-synaptic effects of norepinephrine (NE), exerted at a cellular or neural circuit level, have been described as modulatory in nature, as NE facilitates responses evoked in target cells by both excitatory and inhibitory afferent input. Over the past few years, we have undertaken a series of studies to understand how these cellular modulatory effects of NE, elicited by acute stress, might translate into modulation of the behavioral-affective components of the whole-animal response to stress. Using microdialysis, we have demonstrated that acute immobilization stress activates NE release in a number of stress-related limbic forebrain target regions, such as the central and medial amygdala, lateral bed nucleus of the stria terminalis, medial prefrontal cortex, and lateral septum. Using microinjections of adrenergic antagonist drugs directly into these regions, we have shown that this stress-induced release of NE facilitates a number of anxiety-like behavioral responses that are mediated in these regions, including stress-induced reduction of open-arm exploration on the elevated plus-maze, stress-induced reduction of social interaction behavior, and activation of defensive burying behavior by contact with an electrified probe. Dysregulation of the brain noradrenergic system may be a factor in determining vulnerability to stress-related pathology, or in the interaction of genetic vulnerability and environmental sensitization. Compared to outbred Sprague-Dawley rats, we have shown that the modulatory effect of NE is deficient in Wistar-Kyoto rats, which also exhibit attenuated behavioral reactivity to acute stress, as well as increased vulnerability to stress-induced gastric ulcers and exaggerated activation of the hypothalamic-pituitary-adrenal (HPA) stress axis. Further, repeated exposure to mild intermittent cold stress resulted in a much greater sensitization of both the brain noradrenergic system and the HPA axis in Wistar-Kyoto rats compared to Sprague-Dawley rats. The recruitment of a robust noradrenergic facilitatory influence following repeated cold exposure in this previously deficient strain resulted in an aberrant HPA response, which may be illustrative of the kinds of neurobiological changes that may contribute to the development of stress-related neuropsychiatric disorders such as depression, post-traumatic stress disorder, or other anxiety disorders in predisposed or susceptible individuals. On the other side of the same issue, regulatory alterations in noradrenergic neurotransmission, or in the stress-modulatory functions of NE, may be important in the behavioral effects of chronic antidepressant drug treatment. We present recent preliminary results addressing the effects of chronic treatment with the selective NE reuptake inhibitor, desipramine, on acute behavioral reactivity to stress. A better understanding of the role of NE in adaptive responses to acute stress, the pathological consequences of prolonged, repeated or severe stress, and the mechanisms of action of drugs used to treat stress-related diseases, may contribute to the future development of more effective strategies for the treatment or even prevention of such disorders.
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PMID:Role of brain norepinephrine in the behavioral response to stress. 1622 65

Research has suggested that rescue workers are at increased risk for psychological distress. To determine whether 9/11 deployment was a significant risk factor for canine search and rescue handlers, 82 deployed handlers were compared to 32 nondeployed handlers on measures of posttraumatic stress disorder (PTSD), depression, anxiety, acute stress, and clinical diagnoses. Deployed handlers reported more PTSD and general psychological distress 6 months after 9/11. Among deployed handlers, prior diagnoses and peritraumatic reactions were associated with psychological distress whereas social support and training were protective. Results suggest that more extensive screening and prophylactic interventions for individuals with a history of mental illness could be beneficial. Future research should examine identified risk/resilience factors prospectively, and training and intervention should be designed accordingly.
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PMID:Risk and resilience in canine search and rescue handlers after 9/11. 1628 Dec 48

This study investigated the predictors of posttraumatic stress disorder (PTSD) following a diagnosis of cancer. Individuals who were recently diagnosed with 1st onset head and neck or lung malignancy (N = 82) were assessed within 1 month of diagnosis for acute stress disorder (ASD) and other psychological responses including depression; individuals were reassessed (N = 63) for PTSD 6 months following their cancer diagnosis. At the initial assessment ASD was diagnosed in 28% of participants, and 22% met criteria for PTSD at 6-months follow-up. Peritraumatic dissociative symptoms at the time of receiving one's cancer diagnosis was the sole predictor of PTSD severity at 6-months follow-up. Elevated dissociative symptoms and greater distress at the initial assessment were the best predictors of PTSD caseness at 6-months follow-up. This study provides evidence for identifying recently diagnosed cancer patients who may benefit from psychological assistance in order to prevent chronic psychopathology.
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PMID:Predictors of posttraumatic stress disorder following cancer. 1628 3

To assess the rapidly changing psychological status of nurses during the acute phase of the 2003 SARS outbreak, we conducted a prospective and periodic evaluation of psychiatric morbidity and psychological adaptation among nurses in SARS units and non-SARS units. Nurse participants were from two SARS units (regular SARS [N=44] and SARS ICU [N=26]) and two non-SARS units (Neurology [N=15] and CCU [N=17]). Participants periodically self-evaluated their depression, anxiety, post-traumatic stress symptoms, sleep disturbance, attitude towards SARS and family support. Results showed that depression (38.5% vs. 3.1%) and insomnia (37% vs. 9.7%) were, respectively, greater in the SARS unit nurses than the non-SARS unit nurses. No difference between these two groups was found in the prevalence of post-traumatic stress symptoms (33% vs. 18.7%), yet, three unit subjects (SARS ICU, SARS regular and Neurology) had significantly higher rate than those in CCU (29.7% vs. 11.8%, respectively) (p<0.05). For the SARS unit nurses, significant reduction in mood ratings, insomnia rate and perceived negative feelings as well as increasing knowledge and understanding of SARS at the end of the study (all p<0.001) indicated that a gradual psychological adaptation had occurred. The adjustment of nurses in the more structured SARS ICU environment, where nurses care for even more severely ill patients, may have been as good or better than that of nurses in the regular SARS unit. Occurrence of psychiatric symptoms was linked to direct exposure to SARS patient care, previous mood disorder history, younger age and perceived negative feelings. Positive coping attitude and strong social and family support may have protected against acute stress. In conclusion, the psychological impact on the caring staffs facing future bio-disaster will be minimized with lowered risk factors and a safer and more structured work environment.
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PMID:Prevalence of psychiatric morbidity and psychological adaptation of the nurses in a structured SARS caring unit during outbreak: a prospective and periodic assessment study in Taiwan. 1646 Jul 60


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