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)

The lifetime prevalence of mood disorders in women is approximately twice that of men. The underlying causality of this gender difference is not yet understood. There is increasing scientific attention to the modulation of the neuroendocrine system by fluctuating gonadal hormones. This review attempts to summarize our current state of knowledge on the role and potential relevance of estrogen and other sex steroids to psychiatric disorders specific to women from menarche to menopause. The sudden appearance of higher levels of estrogen in puberty alters the sensitivity of the neurotransmitter systems. Moreover, the constant flux of estrogen and progesterone levels throughout the reproductive years portends constant modification of the neurotransmitter systems. Premenstrual syndromes may be the result of an altered activity or sensitivity of certain neurotransmitter systems. Pregnancy and delivery produce dramatic changes in estrogen and progesterone levels as well as significant suppression along the HPA axis, possibly increasing vulnerability to depression. At menopause, estrogen levels decline while pituitary LH and FSH levels increase. The loss of modulating effects of estrogen and progesterone may underlie the development of perimenopausal mood disorders in vulnerable women. The pattern of neuroendocrine events related to female reproduction is vulnerable to change and is sensitive to psychosocial, environmental, and physiological factors. Further research is needed to be able to identify specific genetic markers which might help us better understand how the balance between estrogen, progesterone, testosterone, and other steroid hormones affect neurotransmitter function.
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PMID:Hormones and mood: from menarche to menopause and beyond. 1264

Early stress is associated with long-term alterations in brain circuits and systems that mediate the stress response. Early stressors have lasting effects on the HPA axis and norepinephrine systems. Other brain systems that are involved include benzodiazepine, opiate, dopaminergic, and various neuropeptide systems. These neurochemical systems modulate function in brain regions, including the hippocampus, amygdala, and prefrontal cortex. Long-term alterations in these brain regions are hypothesized to play a role in the maintenance of PTSD, depression, and other psychiatric symptoms after childhood abuse.
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PMID:Long-term effects of childhood abuse on brain and neurobiology. 1272 12

Several studies have suggested an association between IgE-mediated atopic allergies and depression. The present study extends our understanding about putative gender differences of this association and provides further epidemiological evidence for our previous finding that the association between atopy and depression may be characteristic for females only. In order to clearly determine the presence of atopic disorders and depression, we used more valid tools than had been employed earlier and we had access to a database (the Northern Finland 1966 Birth Cohort), in which individuals were followed up prospectively until the age of 31 years. The information on allergic symptoms, verified by skin-prick tests and comprising data of 5518 individuals, was used to ascertain the presence of atopy. Depression was assessed with the help of Hopkins' Symptom Checklist-25 and self-reported doctor-diagnosed depression. After adjusting for a father's social class, mother's parity, and place of residence, logistic regression analyses showed that the risk of developing depression increased in parallel with the increasing severity of depression and, when compared with nonatopic subjects, was 3.0 to 4.7-fold up in atopic females and statistically significant. In atopic males, the association between atopy and depression was statistically significant only in the highest depression scores, the odds ratio being 6.3-fold. The results indicate that females suffering from atopic diseases might possess an elevated risk of developing depression already during early adulthood. In males, the association between these two disorders is evident only among the most severe manifestations of depression. Possible background theories, that is, genetic abnormalities in serotonin metabolism, HPA-axis dysfunction, and histamine theory are discussed.
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PMID:Atopy and depression: results from the Northern Finland 1966 Birth Cohort Study. 1288 95

To model aspects of trait anxiety/depression, Wistar rats were bred for extremes in either hyper (HAB)- or hypo(LAB)-anxiety as measured on the elevated plus-maze and in a variety of additional behavioral tests. Similar to psychiatric patients, HAB rats prefer passive stress-coping strategies, indicative of depression-like behavior, show hyper-reactivity of the hypothalamo-pituitary-adrenal axis, and a pathological response to the dexamethasone/corticotropin-releasing hormone (CRH) challenge test. Here we tested central mRNA expression, release patterns, and receptor binding of neuropeptides critically involved in the regulation of both anxiety-related behavior and the HPA axis. Thus, CRH, arginine-8-vasopressin (AVP), and oxytocin (OXT) were studied in brains of HAB and LAB males both under basal conditions and after exposure to a mild emotional stressor. In HAB rats, CRH mRNA was decreased in the bed nucleus of the stria terminalis only. While no significant difference in CRH1-receptor binding was found in any brain area, CRH2-receptor binding was elevated in the hypothalamic paraventricular nucleus (PVN), the ventromedial hypothalamus, and the central amygdala of HABs compared to LABs. AVP, but not OXT, mRNA expression as well as release of the neuropeptide, were higher in the PVN of HABs, whereas AVP V1a-receptor binding failed to show significant differences in any brain region studied. Remarkably, intra-PVN treatment of HABs with the AVP V1-receptor antagonist d (CH(2))(5) Tyr (Me) AVP resulted in a decrease in anxiety/depression-related behavior. The elevated expression and release of AVP within the PVN of HAB rats together with the behavioral effects of the AVP V1-receptor antagonist suggest a critical involvement of this neuropeptide in neuroendocrine and behavioral phenomena associated with trait anxiety/depression.
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PMID:Alterations in central neuropeptide expression, release, and receptor binding in rats bred for high anxiety: critical role of vasopressin. 1294 43

Present experiments in rats were aimed to verify the hypothesis that glutamatergic neurotransmission and stress hormones play a role in impairment of hedonic behavior, a sign of depression-like state. On the basis of individual variability in sucrose preference, test rats were divided into anhedonic and hedonic groups. Anhedonic animals showed higher basal concentrations of adrenocorticotropin and corticosterone but reduced hormonal responses during novelty stress compared to hedonic animals. Acute administration of citalopram (10 mg/kg ip) induced similar effects in both groups. Corticotropin-releasing hormone (CRH) mRNA levels in hypothalamic paraventricular nucleus (PVN) were higher in anhedonic rats. Oxytocin (OT) and vasopressin gene expression in the PVN and proopiomelanocortin (POMC) expression in the anterior pituitary failed to show any significant differences. Gene expression of NR1 receptor subunit of N-methyl-D-aspartate (NMDA) glutamate receptor in the ventral tegmental area (VTA) was found to be lower in anhedonic rats. In the nucleus accumbens (NAc) and the hippocampus of anhedonic animals, higher mRNA levels of NR2A subunit compared to those of hedonic rats were detected. Thus, low sucrose preference is associated with altered HPA axis activity, NMDA receptor subunits and CRH gene expression in selected brain regions. These mechanisms may operate in the disposition to develop hedonic deficit in some mental disorders.
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PMID:Altered glutamate receptor and corticoliberin gene expression in brain regions related to hedonic behavior in rats. 1367 12

For now more than 50 years, lithium has been the gold standard for the pharmacologic treatment of bipolar disorder. However, its utility is not restricted to acute mania and prophylactic treatment of bipolar disorder. A relatively new indication for its use is the addition to an antidepressant in the acute treatment phase of unipolar major depression. To date, this treatment approach called lithium augmentation is the best-documented approach in the treatment of refractory depression. In international treatment guidelines and algorithms, lithium augmentation is considered a first-line treatment strategy for patients with a major depressive episode who do not adequately respond to standard antidepressant treatment. In a recent double-blind, placebo-controlled trial, lithium augmentation has demonstrated to also be effective in the continuation treatment phase to prevent early relapses. From animal studies there is robust evidence that lithium augmentation increases serotonin (5-HT) neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways. In contrast to the established decline of HPA system activity during treatment with tricyclic antidepressants, neuroendocrine studies on the effects of lithium augmentation on the HPA system showed an unexpected and marked increase in the ACTH and cortisol response in the combined DEX/CRH test. Here we review new data on the efficacy and mechanism of action of lithium augmentation.
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PMID:Lithium augmentation in treatment-resistant depression: clinical evidence, serotonergic and endocrine mechanisms. 1467 84

The importance of sex differences in major affective diseases such as depression is providing a new focus for investigating the interactions between sex, sex steroids and antidepressants. In this study, we examined the acute effects of sertraline, a selective serotonin reuptake inhibitor (SSRI) and imipramine, a tricyclic antidepressant (TCA) on the endocrine endpoints, adrenocorticotropin (ACTH) and cortisol secretion in gonadectomised male and female sheep. Each sheep was treated with an acute subcutaneous (s.c.) injection containing vehicle, sertraline (5 and 10 mg/kg), or imipramine (10 mg/kg) in the presence and absence of sex steroid replacement. In males, SSRI treatment consisted of testosterone (2 x 200 mg s.c. pellets), and in females, estradiol (1 cm s.c. implant) plus an intravaginal controlled internal drug release device containing 0.3 g progesterone. ACTH and cortisol were measured in jugular blood. Female sheep responded to sertraline treatment with dose-dependent ACTH and cortisol increases that were unchanged by sex steroid replacement. In castrated males, however, only the highest dose of sertraline increased ACTH and cortisol, and this increase was abolished in the presence of testosterone replacement. Imipramine affected neither ACTH nor cortisol secretion in either the sex or sex steroid condition. We conclude that the sex and sex steroid-related differences in the male and female responses to sertraline treatment may reflect sex and sex steroid dependent differences in serotonergic activation of the HPA axis. This highlights the potential significance of sex and circulating sex steroids in modulating neuroendocrine responses to antidepressants, and may have an impact on our understanding of the actions of these drugs in men and women.
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PMID:Antidepressants, sex steroids and pituitary-adrenal response in sheep. 1499 76

Preliminary evidence shows that ethyl-eicosapentaenoate (E-EPA) has a marked clinical effect when used as an adjunct in therapy-refractory depression. EPA belongs to the class of polyunsaturated omega-3 fatty acids. The mechanism of its action in depression is not fully understood. There are two related fields where the pathophysiology of refractory depression meets the effect of EPA. First, a general immunosuppressive effect of EPA meets a general immunoactivation in severe depression, especially an increase in CD4/CD8 ratio, neutrophilia, and an increase in interleukins (IL)-6 and IL-12 and of prostaglandin E2 (PGE2). Secondly, a resistance to dexamethasone (Dex) suppression of the HPA axis meets the effects of EPA on multidrug resistance reversing and HPA axis suppression. The effects of EPA on the immune system, the HPA axis, and multidrug resistance are connected through the action of a transport protein called p-glycoprotein (p-gp). Physiological and synthetic steroids such as cortisol and Dex are substrates of p-gp, and so Dex resistance in depression may be related to dysfunction of this protein. In addition, expression of p-gp is induced by PGE2, and EPA inhibits the synthesis of PGE2. The reversal of drug resistance by EPA may be mediated via this immunological mechanism and lead to its antidepressive efficacy. In addition, antidepressants such as amitriptyline, which have special efficacy in severe depression, decrease p-gp function. EPA may, furthermore, enhance the action of antidepressants, like many SSRIs that are p-gp substrates, which are actively transported out of the intracerebral space at the level of the blood-brain barrier.
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PMID:Ethyl-eicosapentaenoate and dexamethasone resistance in therapy-refractory depression. 1500 46

Patients diagnosed with certain anxiety disorders or depression show symptoms of a dysregulated HPA-axis secondary to increased release of corticotropin releasing factor (CRF). Male Wistar rats were injected with CRF (100 ng/microL) in the basolateral amygdala (BLA) for 5 days. Measurement of behavior was performed on the elevated plus maze and open field test. Behavioral and neuroendocrine response to restraint stress was also evaluated. Chronic treatment of CRF resulted in a significant increase in grooming after restraint stress in the Open Field test. Basal plasma corticosterone concentrations were significantly lower in the CRF-injected rats. These animals also showed greater and longer increase in corticosterone levels following the restraint stress than controls, but had comparable ACTH responses to restraint stress. Our results indicate that chronic administration of CRF into the basolateral amygdala may promote stress-induced grooming behavior in rats. In addition the data suggests that increased CRF in the amygdala may contribute to the dysregulation of corticosterone secretion. These findings may have important implications for patients suffering from psychiatric illnesses such as posttraumatic stress disorder and depression that are characterized by abnormalities in cortisol release.
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PMID:The effects of repeated intra-amygdala CRF injections on rat behavior and HPA axis function after stress. 1521 2

We propose that sex differences in HPA regulation may emerge during puberty and help to explain sex differences in depression. In this study, we examined sex differences in cortisol responses to CRH challenge across pubertal stages in carefully screened control subjects from the Pittsburgh Psychobiologic Studies. Participants were 7-16 years of age, physically healthy, and had no personal or family history of psychiatric disorder. Physician-rated Tanner staging was conducted, followed by CRH challenge sessions including 30-40 minutes pre-infusion baseline, 1 microg/kg CRH infusion, 90-180 minutes of post-infusion measures, and 9-10 plasma cortisol samples. Girls showed increasing total cortisol responses to CRH across Tanner stages, explained by slower recovery from peak cortisol levels, while boys showed similar total responses across Tanner stages. Results show subtle sex differences in the influence of puberty on HPA regulation at the pituitary level, which may represent one factor underlying the emergence of girls' greater rates of depression during this time.
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PMID:Sex differences in the effects of pubertal development on responses to a corticotropin-releasing hormone challenge: the Pittsburgh psychobiologic studies. 1525 8


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