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 hypothalamic-pituitary-adrenal (HPA) axis and the female reproductive system are intertwined and exhibit a complex relationship. Thus, the HPA axis exerts profound, mostly inhibitory effects, on the reproductive axis, with corticotropin-releasing hormone (CRH) and CRH-induced propiomelanocortin peptides inhibiting hypothalamic GnRH secretion, and with glucocorticoids inhibiting pituitary LH and ovarian estrogen and progesterone secretion and rendering estrogen-target tissues, such as the endometrium, resistant to the gonadal steroid. These effects of the HPA axis are responsible for the "hypothalamic" amenorrhea of stress, depression and eating disorders, and the hypogonadism of Cushing's syndrome. Conversely, estrogen directly stimulates the CRH gene, which may explain the slight hypercortisolism of females and the preponderance of depressive, anxiety, and eating disorders, as well as Cushing's disease in women. Interestingly, several components of the HPA axis and their receptors are present in reproductive tissues, as autocoid regulators of their various functions. These include ovarian and endometrial CRH, which may participate in the inflammatory processes of the ovary, that is, ovulation and luteolysis, and of the endometrium, that is, implantation and menstruation. Finally, the hypercortisolism of the latter half of pregnancy can be explained by high levels of placenta CRH in plasma. This hypercortisolism causes a transient adrenal suppression in the postpartum period, which may explain the postpartum blues/depression and autoimmune phenomena of this period.
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PMID:The hypothalamic-pituitary-adrenal axis and the female reproductive system. 923 54

The hypercortisolism of melancholic depression is thought to reflect hypothalamic hypersecretion of CRH and may be related to the hyperarousal associated with this syndrome. Although chronic administration of imipramine to experimental animals significantly decreases CRH messenger RNA levels in the paraventricular nucleus, it is generally thought that resolution of hypercortisolism following recovery from depression is related to the improvement in mood and decrease in anxiety that accompanies recovery rather than an intrinsic effect of imipramine. The present study was designed to explore whether chronic imipramine administration to healthy, nondepressed volunteers is associated with effects on hypothalamic-pituitary-adrenal (HPA) axis function. We studied basal and provocative measures of HPA axis function in 14 healthy volunteers before and after 6 weeks of imipramine treatment at therapeutic doses. Imipramine was associated with decreased responses in peak ACTH and cortisol to ovine CRH and in peak ACTH to arginine vasopressin (P = 0.02, P = 0.003, and P = 0.02, respectively) without changes in indices of basal HPA axis function. These data are consistent with preclinical findings and support the hypothesis that imipramine has an intrinsic effect on central components of HPA axis function, potentially related to its therapeutic effects.
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PMID:Chronic imipramine is associated with diminished hypothalamic-pituitary-adrenal axis responsivity in healthy humans. 925 41

In major depression there are two well-documented biochemical abnormalities: hypercortisolism, and its resistance to dexamethasone suppression. It therefore seems reasonable to see if giving drugs which interfere with cortisol biosynthesis might bring about a remission. An open trial was begun in our institution of 20 refractory patients with major depression. Aminoglutethimide, metyrapone, ketoconazole or combinations of these drugs along with a maintenance dose of cortisol were used for eight weeks. Of the 17 completers, eleven patients were considered to have good responses and two partial responses. Four had complete remissions lasting several years. A similar study of four patients who received oral RU 486 also gave encouraging results. Two patients with obsessive compulsive disorder associated with depression showed striking improvement on aminoglutethimide combined with a serotonin re-uptake inhibitor. In addition to a case report in 1988 by Ravaris et al. of a patient hypophysectomized for previous Cushing's syndrome whose depression responded to ketoconazole, several other studies over the past five years have had similar favorable results. Wolkowitz et al. (1993) gave oral ketoconazole to 10 depressed patients for three weeks which resulted in a significant drop in their Hamilton Depression Scale ratings. O'Dwyer et al. (1995) conducted a placebo-controlled single-blind crossover study using lifetyrapone and maintenance cortisol in eight inpatients for two weeks; six responded. Thakore and Dinan (1995) studied eight inpatients using ketoconazole for four weeks; there were five responders and three partial responders. Anand et al. (1995) conducted a four-week double-blind trial of ketoconazole in a single treatment-refractory patient with good results. Arana et al. (1995) used a different approach but one which also leads to suppression of endogenous corticosteroids-i.e. short-term dexamethasone suppression (4 mg/day for four days). When tested at 14 days, 7/19 of the dexamethasone group had responded well while only 1/18 of the placebo group had responded. While these studies have shortcomings, antiglucocorticoid therapy appears to be an effective tool in the treatment of major depression. Possible mechanisms are discussed, and a unifying hypothesis is attempted.
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PMID:Antiglucocorticoid therapies in major depression: a review. 926 59

The overnight dexamethasone (DXM) test can give false-positive results in a few conditions (e.g. stress, strenuous exercise, depression, anorexia, anxiety, anticonvulsive therapy) in diagnosing simple obesity and hypercortisolism (HC). The loperamide (LP; a peripheral opioid agonist) test has proven useful in such conditions in adults. Thirty-one obese subjects (age 10.0-19.7 y) were studied by both overnight DXM test and LP test (8 mg orally, samples for cortisol at 0, 90, 150, 180 and 210 min) on 2 separate days. LP suppressed cortisol (< or = 138 nmol l-1) at a dose of 0.1 mg kg-1 bw (half the minimum recommended dose for the drug's antidiarrhoea effect) in 14 subjects who had normal urinary (< 4970 nmol l-1) and serum (< 552 nmol l-1) cortisol, in the absence of signs and symptoms of HC (group A). The DXM test failed to suppress cortisol in three subjects in group A, two of whom were on anticonvulsive treatment. The LP test suppressed cortisol in all of 13 subjects with elevated urinary and/or serum cortisol and/or with signs or symptoms of HC (but in whom HC was subsequently excluded on clinical grounds) (group B), while the DXM test failed to suppress cortisol in three subjects of this group. One of these was under anticonvulsive treatment and one suffered from anxiety and depression. In four patients with Cushing's syndrome (group C) neither DXM nor LP could suppress cortisol levels. Therefore, the sensitivity was 100% for both DXM and LP, while the specificity was 84% for DXM and 100% for LP. No side-effects were observed with either drug. In conclusion, LP is a useful alternative to DXM in those particular conditions that can affect its specificity in children.
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PMID:Loperamide test: a simple and highly specific screening test for hypercortisolism in children and adolescents. 940 9

Depression and distress have in common hypercortisolism, a high turn-over of cerebral monoamines and a wide clinical variability. Results of a clinical open trial with pivagabine (4-[(2,2-dimethyl-1-oxopropyl) amino]butanoic acid, CAS 69542-93-4, Tonerg) on 22 young patients affected by dysthymic disorders and on 38 older patients affected by adjustment disorders following different stressors (mourning, retirement and recovery in institutions of assistance) are reported. Oral treatment with 1800 mg pivagabine lasting 30 days showed in both groups a significant improvement of the psychic state with variations from 50 to 80% of the criteria reported in the Hamilton Rating Scale for Depression (HDRS) and for anxiety (HARS) and in the Self-rating Anxiety Scale (SAS). Good tolerance of the drug and the complete absence of serious side effects considerably contributed to the clinical success.
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PMID:Clinical evaluation of the efficacy of pivagabine in the treatment of mood and adjustment disorders. 945 Jan 58

Preclinical studies of inflammatory and autoimmune illnesses have demonstrated the importance of central components of the HPA axis in disease pathophysiology. The implications of these data for human illness are poorly understood. We have studied the pathophysiology of the hypercortisolism seen in two human illnesses involving the central nervous system, multiple sclerosis (MS) and depression, and looked for demonstrable somatic changes that may be associated with such hypercortisolism. Data from a study of medication-free patients with multiple sclerosis not in acute exacerbation suggest that compared with depression, MS is associated with increased prominence of hypothalamic vasopressin secretion (p < 0.05). Data from studies of depressed patients with mild to moderate hypercorticolism (assessed by 24-hour urinary free cortisol excretion) demonstrate marked reductions in bone mineral density compared to healthy, carefully matched controls (p < 0.001), as well as changes in markers of bone metabolic activity similar to those seen in patients with Cushing's disease or exogenous glucocorticoid treatment (p < 0.05). Taken together, these studies suggest HPA axis dysregulations demonstrated in preclinical models of autoimmune and inflammatory illness also occur in human illness and may have important and lasting somatic sequelae.
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PMID:Pathophysiologic and somatic investigations of hypothalamic-pituitary-adrenal axis activation in patients with depression. 962 98

The hypothalamic-pituitary-adrenal axis exerts profound, multilevel inhibitory effects on the female reproductive system. Corticotropin-releasing hormone (CRH) and CRH-induced proopiomelanocortin peptides inhibit hypothalamic gonadotropin-releasing hormone secretion, whereas glucocorticoids suppress pituitary luteinizing hormone and ovarian estrogen and progesterone secretion and render target tissues resistant to estradiol. The hypothalamic-pituitary-adrenal axis is thus responsible for the "hypothalamic" amenorrhea of stress, which is also seen in melancholic depression, malnutrition, eating disorders, chronic active alcoholism, chronic excessive exercise, and the hypogonadism of the Cushing syndrome. Conversely, estrogen directly stimulates the CRH gene promoter and the central noradrenergic system, which may explain adult women's slight hypercortisolism; preponderance of affective, anxiety, and eating disorders; and mood cycles and vulnerability to autoimmune and inflammatory disease, both of which follow estradiol fluctuations. Several components of the hypothalamic-pituitary-adrenal axis and their receptors are present in reproductive tissues as autacoid regulators. These include ovarian and endometrial CRH, which may participate in the inflammatory processes of the ovary (ovulation and luteolysis) and endometrium (blastocyst implantation and menstruation), and placental CRH, which may participate in the physiology of pregnancy and the timing of labor and delivery. The hypercortisolism of the latter half of pregnancy can be explained by high levels of placental CRH in plasma. This hypercortisolism causes a transient postpartum adrenal suppression that, together with estrogen withdrawal, may partly explain the depression and autoimmune phenomena of the postpartum period.
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PMID:Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. 969 32

Leptin, the protein product of the obese (ob) gene, has been suggested to play a role in the regulation of food intake. As depressive episodes are frequently characterized by loss of appetite, reduced food intake and weight loss, altered leptin secretion might also be expected in patients with depression. Therefore, we examined nocturnal (10.00 p.m. to 7.00 a.m.) secretion of leptin, cortisol, ACTH and growth hormone (GH) in a group of 15 patients with depression and age- and sex-matched controls (age range 23-71 years). In addition, the effects of pulsatile administration of growth hormone-releasing hormone (GHRH), thought to be an endogenous antagonist of corticotropin-releasing hormone (CRH), which in turn is believed to play a critical role for the pathophysiology of depression, on nocturnal hormone secretion were assessed. Patients with depression showed a trend towards elevated nocturnal cortisol secretion (F = 3.8, p < 0.05). Nocturnal serum leptin was significantly higher in patients, despite a reported weight loss (F = 8, p < 0.05), but showed the same sexual dimorphism as in controls (F = 20.9, p < 0.01). No significant differences were seen between patients and controls with regard to plasma GH and ACTH. GHRH treatment increased GH secretion in both patients and controls, while the other hormones were not affected. Furthermore, serum leptin was correlated with body mass index (BMI) in controls, but not in patients with depression, supporting an altered regulation of leptin secretion in depressive illness. Finally, we provide some evidence that in young female patients the normal nocturnal leptin surge is blunted. As glucocorticoids can prevent the fasting-induced decline in serum leptin, we propose that hypercortisolism in depression might counteract the reduction in leptin secretion caused by decreased food intake and weight loss. Elevated serum leptin in depression might in turn further promote CRH release, as shown in animals and, hence, contribute to HPA system hyperactivity seen in depression.
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PMID:Elevated nocturnal profiles of serum leptin in patients with depression. 984 57

Posttraumatic stress disorder is the pathological replay of emotional memory formed in response to painful, life-threatening, or horrifying events. In contrast, depression is often precipitated by more social context-related stressors. New data suggest that different types of life experiences can differentially impact biochemistry, physiology, anatomy, and behavior at the level of changes in gene expression. Repeated separation of neonatal rat pups from their mother results in many long-lasting alterations in biology and behavior paralleling that in depression, including hypercortisolism. The role of the amygdala in modulating emotional memory is highlighted, as well as some of its unique properties such as metaplasticity (i.e., the differential direction of long-term adaptation, either potentiation or depression) in response to the same input as a function of the prior history of stimulation. The implications of these emerging data on the physiological and molecular mechanisms underlying emotional memory emphasize the particular importance of prevention and early intervention.
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PMID:Neural plasticity and emotional memory. 988 29

The cardinal clinical manifestations of major depression with melancholic features include sustained anxiety and dread for the future as well as evidence of physiological hyperarousal (e.g., sustained hyperactivity of the two principal effectors of the stress response, the corticotropin-releasing-hormone, or CRH, system, and the locus ceruleus-norepinephrine, or LC-NE, system). Sustained stress system activation in melancholic depression is thought to confer both behavioral arousal as well as the hypercortisolism, sympathetic nervous system activation, and inhibition of programs for growth and reproduction that consistently occur in this disorder. Data also suggest that activation of the CRH and LC systems in melancholia are involved in the long-term medical consequences of depression such as premature coronary artery disease and osteoporosis, the two-three-fold preponderance of females in the incidence of major depression, and the mechanism of action of antidepressant drugs. In addition, recent data reveal important bidirectional interactions between stress-system hormonal factors in depression and neural substrates implicated in many discrete behavioral alterations in depression (e.g., the medial prefrontal cortex, important in shifting affect based on internal and external cues, the mesolimbic dopaminergic reward system, and the amygdala fear system). We have also advanced data indicating that the hypersomnia, hyperphagia, lethargy, fatigue, and relative apathy of the syndrome of atypical depression are associated with concomitant hypofunctioning of the CRH and LC-NE systems. These data indicate the need for an entirely different therapeutic strategy than that used in melancholia for the treatment of atypical depression, and they suggest that this subtype of major depression will be associated with its own unique repertoire of long-term medical consequences.
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PMID:The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. 989 54


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