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)

Serotonin N-acetyltransferase (AANAT; EC 2.3.1.87) metabolizes serotonin into N-acetylserotonin (NAS). AANAT mRNA is expressed in the pineal gland and retina, and also in the rat brain. It was proposed that NAS could be a mediator of the antidepressant action of drugs, and it was shown that chronic but not acute treatment of rats with the antidepressant fluoxetine increases the content of AANAT mRNA in the rat hippocampus. Consequently, AANAT deficiency might be involved in the pathobiology of depression. C57BL/6J mice have a mutant AANAT gene and are considered AANAT-deficient, i.e., "knocked down" (compared with their normal counterparts, C3H/HeJ mice). In this study, we investigated whether AANAT mRNA is expressed in the brain of C57BL/6J and C3H/HeJ mice and whether those mice differ behaviorally, i.e., in a forced swimming test which is used to evaluate antidepressant drugs (such drugs shorten the time of immobility). We found that C3H/HeJ mice express in the brain normal AANAT mRNA, whereas C57BL/6J mice express mutated AANAT mRNA. The mutant, AANAT knocked down C57BL/6J mice displayed significantly longer times of immobility ("depression"). This difference was evident regardless of the circadian rhythm, i.e., both during the day and in the dark at night. Further studies are needed to fully characterize the behavioral significance of AANAT mutation and its possible link to depression.
J Pineal Res 2001 Apr
PMID:Prolonged swim-test immobility of serotonin N-acetyltransferase (AANAT)-mutant mice. 1131 27

In the present study, we investigated the ability of serotonin and melatonin to bind metals that occur naturally in the brain. An electrochemical technique called adsorptive cathodic stripping voltammetry (AdCSV) was employed to study the metal-serotonin or metal melatonin interactions. The results show that both serotonin and melatonin form stable complexes with lithium and potassium, with serotonin favouring lithium over potassium, and melatonin favouring potassium over lithium. Coordination between either serotonin or melatonin and calcium was not favoured. The stability of the complexes formed between serotonin and the metals decreased with the metals as follows: Li+ > K+ > Al3+ > Na+ > Ca2-. The trend for melatonin-metal complexes was K+ > Li+ > Na+ > Al3+ > Ca2+ The binding and stable complex formation between both ligands, serotonin and melatonin with lithium, potassium and sodium is of biological importance. The binding of serotonin to lithium could provide an explanation for the therapeutic effects of lithium in depression treatment, whereas the binding of aluminium by melatonin could provide insight into the role of this element in the aetiology of Alzheimer's disease.
J Pineal Res 2001 Sep
PMID:Interaction of serotonin and melatonin with sodium, potassium, calcium, lithium and aluminium. 1155 64

Patients with end-stage renal disease (ESRD) suffer from a number of related disorders. These include endocrine abnormalities, sleep disturbances, and depression. Melatonin is involved in the synchronization of exogenous zeitgebers with the endogenous rhythms, and it has effects on various psychological factors. As the concentrations of melatonin and the effects of dialysis have only occasionally been investigated in ESRD, we performed a study involving 35 patients, measuring the serum concentrations of melatonin, and of its major metabolite 6-sulfatoxymelatonin (aMT6s), before and after hemodialysis. Serum samples taken during morning hours from a control group (n=11) with intact kidneys served as controls. Patients were dialyzed for approximately 4 hr between 07:00 and 13:00 hr (S1), between 13:00 and 20:00 hr (S2), or between 18:30 and 22:30 hr (S3). Mean melatonin concentrations before hemodialysis were highly elevated when compared with the controls (40.6 vs. 6.7 pg/mL; P<0.001). Although melatonin levels were decreased to 20.3 pg/mL after dialysis, they were still well above the control levels. Likewise, aMT6s concentrations before dialysis were highly elevated in ESRD patients before dialysis when compared with controls (39.5 vs. 2.0 pg/mL; P<0.001), and also decreased by dialysis to levels still well above control levels (25.3 pg/mL). Clearance efficacy was better for melatonin (48.9%) than for aMT6s (36.6%; P<0.05). In ESRD patients, a diurnal rhythm for melatonin was observed (S1, 45.1 pg/mL; S2, 31.5 pg/mL; S3, 48.7 pg/mL; P<0.05), indicating that the normal synthesis rhythm is maintained. None of the following secondary disorders were correlated with melatonin concentrations: insomnia, delayed sleep onset, night-time arousals, and restless-leg syndrome. The reason for this observation is probably the melatonin concentrations, which were so high that no sub-classification could be identified. It is concluded that in ESRD patients, hemodialysis is unable to decrease elevated levels of melatonin and aMT6s to normal values. It is speculated that some of the secondary disorders in ESRD are caused by supraphysiological concentrations of melatonin.
J Pineal Res 2001 Oct
PMID:Clearance of melatonin and 6-sulfatoxymelatonin by hemodialysis in patients with end-stage renal disease. 1158 56

This study examined the circadian phase adjustment of symptomatic elders ages 60-79 years in comparison with that of young, healthy adults ages 20-40 years. Seventy-two elders with complaints of insomnia or depression, and 30 young, healthy adults were assessed for 5-7 days at home. Sleep and illumination were recorded with Actillume wrist monitors and sleep diaries. Urine was collected over two 24-hr periods and assayed for 6-sulphatoxymelatonin (6-smt). The volunteers were then observed continuously for 5 nights and 4 days in the laboratory. In the laboratory, sleep periods were fixed at 8 hr with polysomnographic assessment of sleep, apnea-hypopnea, and nocturnal myoclonus. Circadian dispersion, defined as the mean variation of 6-smt acrophase from the median age-specific acrophase, was significantly greater in the older vs. young adults. Likewise, circadian malsynchronization, defined as the absolute number of hours (advance or delay) between the 6-smt acrophase and the middle of the sleep period, was significantly greater in the older vs. young volunteers. For the older volunteers, multiple regressions were calculated associating sleep with potential correlates of sleep disturbance. Nocturnal myoclonus and circadian malsynchronization were more strongly associated with sleep impairment than other factors (e.g., sleep apnea, depression). These observations suggest that circadian malsynchronization might be a common and significant cause of disturbed sleep among adults over age 60.
J Pineal Res 2001 Oct
PMID:Circadian abnormalities in older adults. 1158 62

Recent work in young and middle-aged subjects suggests that melatonin levels in saliva may represent a viable alternative to serum melatonin measurement. We hypothesized that it may be a valid measure of melatonin levels in older adults as well, but features unique to the elderly may limit its utility. To study this, subjects were admitted to an academic medical center where saliva and serum specimens were collected concurrently in dim light conditions during a 14-hr overnight study period and analyzed for melatonin levels with radioimmunoassays (RIAs). Eighty-five subjects over the age of 65 with a broad range of medical conditions participated in the study. Subjects with dementia, depression and anemia were excluded. We found that saliva volume was inadequate for analysis (<200 microL) in 23.6% of specimens, with the majority of inadequate volume specimens occurring after midnight and inadequate specimens occurring more frequently in females than in males. The correlation coefficient for saliva melatonin and serum melatonin was r = 0.659 (Spearman, P < 0.001), and r = 0.466 for saliva dim light melatonin onset (DLMO) and serum DLMO. Saliva melatonin levels were 30.9% of serum melatonin levels, with a wide range of ratios noted between subjects. Overall melatonin levels influenced both the correlation and ratio of saliva melatonin to serum melatonin; higher correlations and lower ratios were noted when melatonin levels were high. Saliva specimens provide an economical and practical method for melatonin assessment, however, in older adults, issues such as hyposalivation and low melatonin levels limit the feasibility and validity, respectively, of saliva melatonin.
J Pineal Res 2003 Mar
PMID:The validity and feasibility of saliva melatonin assessment in the elderly. 1256 99

Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurization may be involved in this effect through disruption of circadian rhythms, independent of the number of time zones crossed. In this controlled crossover study we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the rhythm of plasma melatonin concentrations, a marker of circadian rhythmicity. Sixteen healthy young male volunteers (23-39 years) were exposed in a hypobaric chamber for 8 hr (08:00-16:00 hours) to 8000 ft, followed 4 wk later by 12,000 ft. Plasma melatonin was assayed over two 24-hr cycles (control and hypoxic exposure) every 2 hr in all subjects. We found a significant decrease in the nocturnal melatonin peak after hypoxic exposure at both altitudes, and we found that this effect was age dependent for the 12,000-ft exposure: the decrease was only seen in the younger subjects (23-28 years). Analysis of heart rate variability allowed us to demonstrate that the older and less trained subjects (29-39 yr) in our study exhibited a far greater increase in sympathetic tone than the younger subjects during the 12,000-ft exposure. These results show that hypoxic depression of melatonin secretion may be influenced by individual factors such as age, physical fitness and sympathetic reactivity to hypoxia. Our findings suggest that hypoxia may by itself contribute at least in part to postflight fatigue after long duration flights, and to the clinical disorders of jet lag in transmeridian flights through its effects on the circadian system.
J Pineal Res 2004 Aug
PMID:Hypoxic depression of melatonin secretion after simulated long duration flights in man. 1523 Aug 62

The objective of this study was to evaluate the possibility of selecting genetic variants of plants with enhanced concentrations of the indoleamine melatonin. A germplasm line of the medicinal plant species, St John's wort (Hypericum perforatum L.), with high levels of melatonin was selected in vitro using mutagenized tissues. The germplasm line has remained stable over a 5-yr period and contained >12-fold (1200%) melatonin content compared with the wild-type plant. Melatonin is a ubiquitous, highly conserved molecule with known therapeutic roles in the treatment of sleep disorders, depression, aging, inhibition of cancer cell growth and as a free radical scavenger and antioxidant. The selected melatonin-rich germplasm line of St John's wort may facilitate fundamental studies on melatonin biosynthesis, metabolism and new developments in natural products for treatment of human diseases.
J Pineal Res 2006 Oct
PMID:A melatonin-rich germplasm line of St John's wort (Hypericum perforatum L.). 1694 91

Mild cognitive impairment (MCI) is an etiologically heterogeneous syndrome characterized by cognitive impairment preceding dementia. Approximately 12% of MCI patients convert to Alzheimer's disease (AD) or other dementia disorders every year. In the present report we retrospectively examined the initial and final neuropsychological assessment of 50 MCI outpatients, 25 of whom had received daily 3-9 mg of a fast-release melatonin preparation p.o. at bedtime for 9-18 months. Melatonin was given in addition to the standard medication prescribed by the attending psychiatrist. Patients treated with melatonin showed significantly better performance in Mini Mental State Examination and the cognitive subscale of the Alzheimer's Disease Assessment Scale. After application of a battery of neuropsychological tests including Mattis' test, Digit-symbol test, Trail A and B tasks and the Rey's verbal test, better performance was found in melatonin-treated patients, except for the Digit-symbol test score which remained unchanged. Abnormally high Beck Depression Inventory scores decreased in melatonin-treated patients, concomitantly with an improvement in wakefulness and sleep quality. The results suggest that melatonin can be a useful add-on drug for treating MCI in a clinical setting.
J Pineal Res 2007 Nov
PMID:Possible therapeutic value of melatonin in mild cognitive impairment: a retrospective study. 1791 Jun 9

Melatonin is a neurohormone naturally found in humans. Melatonin plays a role in maintaining sleep-wake rhythms; supplementation may help to regulate sleep disturbance that occur with jet lag, rotating shift-work and depression. Preliminary study of melatonin has shown potential for use in the treatment of epilepsy, tinnitus, migraine and neurodegenerative diseases. The latest publication in the Journal of Pineal Research by Edward Mills and colleagues has shown a compelling role of melatonin for the treatment of cancer. Melatonin's consistent relationship with cancer has been shown in many studies assessing links between shift work and cancer rates. High levels of melatonin have been linked to slower cancer progression. How melatonin affects cancer remains largely unclear. Although previous studies suggest different possible mechanisms, many of them are far distant from the primary physiological role of melatonin as a neurohormone. Conflicting studies are found on the role of melatonin in neurodegenerative diseases and cancer. In this article, we try to build and substantiate a neurobiological concept for the anticancer effects of melatonin.
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PMID:Neurobiological effects of melatonin as related to cancer. 1809 Jan 23

Reperfusion after a short period of cardiac ischemia triggers ventricular arrhythmias attributable to ionic imbalance and oxidative stress. Melatonin offers some degree of protection, but its effects on the cardiac action potentials are unknown. We evaluated the effects of 5, 10, 20 and 50 microM melatonin in isolated perfused rat hearts subjected to 10 min of regional ischemia. ECG and membrane potentials were synchronously displayed. After 15 min of reperfusion, total antioxidant capacity (TAC) was determined. Melatonin did not change the ischemic depolarization nor the action potential amplitude depression, but at the end of ischemia the action potential duration (APD) decreased in control and 5 microM melatonin-treated hearts. By contrast, it returned to preischemic levels in hearts given 20 and 50 microM melatonin. Melatonin reduced the incidence of reperfusion arrhythmias from 100% in control to 50% in 5 and 10 microM, to 40% in 20 microM and 30% in 50 microM hearts. TAC values were higher at all melatonin concentrations. We conclude that melatonin reduced the incidence of reperfusion arrhythmias because of its antioxidant effects. In addition, at 20 and 50 microM lengthened APD and promoted an improved protection. This latter effect should be considered when in vivo applications of melatonin are considered.
J Pineal Res 2009 Mar
PMID:A novel electrophysiologic effect of melatonin on ischemia/reperfusion-induced arrhythmias in isolated rat hearts. 1917 55


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