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. Preclinical studies reveal that long-term treatment with antidepressant drugs induces significant changes in serotonergic (5-HT) receptor sensitivity. Similarly, clinical studies suggest that brain 5-HT function is abnormal in depression. Of the available methodologies for conducting such clinical studies, the pharmacological challenge strategy has proven particularly useful. 2. I.v. L-TRP has emerged as the most frequently used challenge agent in diagnostic and neuropsychopharmacological studies of 5-HT function. I.v. L-TRP increases serum prolactin (PRL) in humans, probably via 5-HT mechanisms. Under carefully standardized conditions, this PRL response to L-TRP appears to be a reasonably sensitive and valid measure of net 5-HT function. 3. The PRL response to L-TRP is blunted in depressed patients compared with healthy controls. Blunting has not been observed in panic disorder, obsessive compulsive disorder, or schizophrenia, although preliminary findings suggest it may occur in bulimia. 4. The PRL response to L-TRP is enhanced by certain classes of thymoleptic drugs (TCAs, MAOIs, 5-HT reuptake inhibitors, lithium) in a differentially time-dependent fashion. So-called "atypical" antidepressants (trazodone, mianserin) and benzodiazepines have no effect. Such findings are generally consistent with preclinical electrophysiological findings. 5. These clinical studies of the PRL response to L-TRP, in conjunction with emerging evidence that experimentally reduced plasma TRP can reverse the therapeutic effects of some antidepressants, suggest that antidepressant drug action may be more accurately conceptualized as 5-HT dependent rather than 5-HT enhancing. The availability of more selective 5-HT-active drugs promises to further clarify 5-HT mechanisms of neuropsychiatric disease and drug action at the clinical level.
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PMID:Clinical studies of 5-HT function using i.v. L-tryptophan. 223 80

Ten male patients with chronic cocaine abuse received a single dose of the dopamine agonist apomorphine. Self-ratings of cocaine craving, depression, and anxiety decreased in response to apomorphine. Neuroendocrine response was consistent with central dopaminergic stimulation. Patients in the "craving" phase of the cocaine abuse cycle differed in behavioral but not neuroendocrine response to apomorphine from patients in the "crash" phase. Decrease in cocaine craving correlated with decrease in plasma homovanillic acid (pHVA). Total cocaine consumption correlated negatively with baseline prolactin and pHVA levels and inversely with peak change in prolactin following apomorphine. Patients had blunted neuroendocrine response to apomorphine in comparison to historical normal controls. Implications for the "dopamine" hypothesis of cocaine abuse are discussed.
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PMID:Dopaminergic sensitivity and cocaine abuse: response to apomorphine. 224 93

To investigate whether depression is a consequence of disturbed function in 5HT systems, neuroendocrine responses to infusions of the 5HT precursor L-tryptophan (LTP) were studied in patients and controls. After an overnight fast and 60 min bed rest, a solution of LTP (10 g/l) was infused intravenously to a dose of 100 mg/kg over 30 min. Circulating growth hormone (GH), prolactin (PRL), cortisol and tryptophan concentrations were followed from 60 min pre-infusion to 60 min post-infusion. GH responses were attenuated in 23 major depressives (DSM-III) compared with 22 controls and were almost absent in endogenous depressives (New-castle criteria). PRL responses were normal in depressives who had lost more than 3 kg body weight but attenuated in those who had not. GH and PRL responses did not correlate with each other. Reduced basal tryptophan concentrations and more rapid tryptophan clearance were observed in the depressives, but there were no correlations with GH or PRL responses. However, basal cortisol concentrations, which were raised in depressives with chronic psychosocial difficulties, were strongly and inversely predictive of PRL responses in depressives and controls. Blunted GH and PRL responses to LTP appear to be distinct abnormalities in depression which may relate to two processes; (1), an endogenous mechanism indicated by reduced GH responses, and (2), an impairment in 5HT systems, indicated by blunted PRL responses and perhaps caused by raised circulating cortisol or reduced tryptophan concentrations.
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PMID:A neuroendocrine study of 5HT function in depression: evidence for biological mechanisms of endogenous and psychosocial causation. 234 77

Forty-four male, neuroleptic-free, acutely psychotic patients with at least one diagnosis of schizophrenia among 11 diagnostic systems, and 28 healthy controls, underwent measurement of prolactin (PRL) concentrations before and after intravenous administration of haloperidol (0.5 mg). Basal PRL concentrations were lower in the patients with Research Diagnostic Criteria (RDC) DSM-III, Cloninger, and Taylor and Abrams schizophrenias than in controls. Compared with the controls, the PRL response to haloperidol was lower in the patients with schizophrenia defined by all diagnostic systems except those of Schneider and M. Bleuler. Neither basal nor stimulated PRL concentrations were correlated with positive symptoms, but basal PRL was correlated with the Brief Psychiatric Rating Scale (BPRS) depression-related subscore. This study lends further support for the presence of dopaminergic dysfunction in schizophrenia, and demonstrates the advantages and problems in the use of multidiagnostic psychopathological evaluation to categorize a disorder where there is major disagreement among diagnostic systems.
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PMID:Basal and haloperidol-stimulated prolactin in neuroleptic-free men with schizophrenia defined by 11 diagnostic systems. 235 27

An influence of early stimulation on sensitivity to acute stress in adulthood has been reported. The purpose of the present work was to determine the effect of exposure of male and female rats to three models of chronic stress (unpredictable stress, cold stress and handling) from day 2 to day 15 of life on behavioral and endocrine sensitivity to chronic stresses in adulthood. The chronic stresses applied in adulthood were a model of intermittent cold stress (daily 30-min sessions at -20 degrees C for 15 days) and the Katz's model of unpredictable chronic stress (15 days). Forced swim behavior and serum concentration of the stress-sensitive hormones, corticosterone and prolactin, were chosen to investigate stress sensitivity. It was found that all neonatal treatments stimulated body weight gain, did not cause infant mortality and did not affect forced swim behavior as adult. The repetitive exposure to cold stress in adulthood did not cause major impairment of forced swim behavior and did not affect basal levels of serum corticosterone and prolactin in either control or experimental rats. These findings support the view that repeated stressors can induce behavioral and endocrine adaptation in rats. The neonatal treatments did not affect this characteristic. The exposure of control rats to the unpredictable stress model severely impaired forced swim behavior and increased basal levels of serum corticosterone and prolactin. This observation conforms to the view that standard laboratory rats cannot adapt to unpredictable chronic stress. This has been reported to cause a behavioral depression syndrome comprising forced swim deficit and endocrine alterations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neonatal chronic stress induces subsensitivity to chronic stress in adult rats. I. Effects on forced swim behavior and endocrine responses. 238 47

Approximately 90% of women experience some symptoms of the premenstrual syndrome (PMS); in up to 40% of cases the symptoms are moderate to severe. The signs and symptoms of PMS usually wax and wane according to a four-phase temporal pattern. Within this overall schema there are a number of PMS subtypes. PMS typically manifests before the age of 30 and rarely resolves spontaneously. While genetic factors may play a role in the development of PMS, other epidemiologic factors do not seem to be involved. Various pathophysiologic mechanisms have been proposed as causing PMS. They are an estrogen/progesterone imbalance, prolactin abnormalities, fluid retention, abnormal production of certain prostaglandins, hypoglycemia, pyridoxine deficiency and shifting levels of endorphins. However, the role of these factors in the etiology of PMS has not been established definitively; thus, treatment remains largely empiric. The author's experience with the use of Danocrine (danazol) on 21 patients with PMS suggests that this synthetic steroid, when used in conjunction with nonpharmacologic treatment options, relieves the symptoms of PMS in up to 85% of patients. Women whose PMS is characterized primarily by mastalgia appear to respond most favorably to treatment; danazol is not recommended for women with primary depression or anxiety symptomatology.
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PMID:Role of danazol in relieving the premenstrual syndrome. 240 19

Biological research in depression has concentrated on 'endogenous' depressions and over the past 30 years has been guided by the amine theory. Neuroendocrine abnormalities in depression have been reported for over 20 years and include changes in the hypothalamic-pituitary-adrenal and thyroid axes, in growth hormone and prolactin secretion. As neurotransmitters regulate neuroendocrine secretion, inter-relationships between neurochemical and neuroendocrine abnormalities may provide a window for understanding the pathophysiology of depression. The availability of these biological markers for depression opens new possibilities for research in psychiatric diagnosis and for management.
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PMID:Neuroendocrine changes in depression. 241 36

There are indications to suggest a relationship between low levels of 5-hydroxy-indoleacetic acid (5HIAA) in the cerebrospinal fluid and suicidal behavior. Many depressed patients show an elevated cortisol secretion. As beta-endorphin is derived from the same precursor as ACTH, it is expected that plasma beta-endorphin levels will also rise in depressed patients. We report here a case of severe depression with diurnal variation who showed low CSF 5HIAA prior to his suicide. In contrast, his catecholamine metabolites were 50% above the mean values of other depressed patients. Hormonal measurements, however, showed low cortisol, prolactin and beta-endorphin levels.
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PMID:Diurnal rhythms of plasma cortisol, beta-endorphin and prolactin, and cerebrospinal fluid amine metabolite levels before suicide. Case report. 243 87

This study sought to identify differences in serum hormone levels between prostatic cancer (CaP) patients, benign prostatic hyperplasia (BPH) patients, and clinic controls (CC). Serum testosterone, estradiol, and prolactin values were obtained from 35 CaP, 42 BPH, and 161 CC patients attending a single medical center between January 1984 and April 1985. Relative risk estimates adjusted for age and race were calculated to compare hormone values between each case group and the CC. The distributions of hormone values and the testosterone to estradiol (T/E) ratios were grouped into thirds with the lowest third forming the reference category. The relative risk estimates for BPH in the middle and high thirds of testosterone were greater than unity (1.26 and 2.10, respectively), whereas the relative risk estimates in the middle and high thirds of estradiol were less than unity (0.63 and 0.35, respectively). For the middle and high thirds of the T/E ratio, the relative risk estimates for BPH showed statistically significant three- to fourfold increases. Modest depression of serum testosterone and estradiol was noted for CaP patients compared to CC, although the differences were not statistically significant. This depression was interpreted to be a likely result of the malignant process rather than a cause of it, whereas the development of clinically evident BPH was felt to be a biologically plausible response to an elevated T/E ratio.
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PMID:Serum hormone levels among patients with prostatic carcinoma or benign prostatic hyperplasia and clinic controls. 244 56

The onset of cessation of oestrous cyclicity and associated organ and hormonal changes were compared in random-bred (RB) and inbred (IB) female Syrian hamsters kept either under short days (8 h light:16 h darkness; 8L:16D) or long days (14L:10D) and given daily afternoon injections of 25 micrograms melatonin. In response to short-day treatment, 100% of the IB hamsters exhibited vaginal acyclicity within 35 days; by comparison, none of the RB animals were acyclic at this time. The IB hamsters also exhibited other changes associated with exposure to short days, including increased body weight, enlarged ovaries, regressed uteri, elevated pituitary concentrations of FSH, and depressed pituitary and plasma concentrations of prolactin. At this time, only the pituitary FSH levels were increased in the RB animals kept under the same short-day conditions. In a second experiment, RB and IB female Syrian hamsters were maintained under long days (14L:10D) and the rate of reproductive regression in response to daily afternoon injections of melatonin was compared. After 8 weeks of melatonin injections, 80% of the IB females were anoestrous, while all RB hamsters were still exhibiting 4-day oestrous cycles. Other changes associated with melatonin administration in the IB females included a marked drop in uterine weight and a depression in pituitary and plasma prolactin levels. The RB hamsters, although they were all still cyclic after 8 weeks, had increased body and ovarian weights, increased pituitary concentrations of FSH, and lower pituitary and plasma prolactin levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rate of reproductive involution following either exposure to short days or daily administration of melatonin is faster in inbred than in random-bred female Syrian hamsters. 249 86


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