Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melatonin secretion has been suggested as a marker of both circadian and noradrenergic dysfunction in affective disorders. Seventy-two newly admitted psychiatric inpatients [49 with major depressive disorder (MDD), 12 with schizophrenia, and 11 with intermittent depressive disorder (IDD)] underwent neuroendocrine screening at 0200, 0800, 1600 and 2300 hours prior to and the day following dexamethasone administration. All groups showed a drop in cortisol following dexamethasone. Dexamethasone nonsuppression was found in 20 of 49 patients with MDD, in none of the schizophrenics and in none of those with intermittent depressive disorder. Mean melatonin levels decreased significantly after the administration of dexamethasone across all four groups. Overall, the schizophrenic group had a significantly greater mean melatonin level than each of the other three groups, whereas the three depressive groups did not differ significantly from one another. Only at 2300 hours did both the schizophrenic group and the MDD patients with normal dexamethasone suppression show significantly greater melatonin levels than the MDD patients with dexamethasone nonsuppression or the IDD group. The observed trend for a low circadian melatonin profile in IDD patients with superimposed personality disorders is puzzling.
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PMID:Nocturnal melatonin and cortisol secretion in newly admitted psychiatric inpatients. Implications for affective disorders. 214 98

Melatonin is produced in the pineal gland. Its involvement in various psychiatric and somatic diseases has been suggested. We investigated melatonin in cerebrospinal fluid of 16 healthy controls, 15 paranoid schizophrenics being treated with neuroleptics, and 13 unmedicated paranoid schizophrenics. There were no significant differences in melatonin concentrations among these three groups. No significant correlations were found between melatonin concentrations and various other biochemical substances such as noradrenalin, cyclic adenosine 3', 5'-monophosphate, prolactin, and cortisol. These negative results do not support the suggestion that melatonin is involved in the etiology of schizophrenia. However, other possibilities, e.g., a change of biological rhythms and its influence on other neuroendocrine functions, may be of importance.
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PMID:Melatonin immunoreactivity in cerebrospinal fluid of schizophrenic patients and healthy controls. 614 34

Recent clinical studies have suggested that treatment with atypical antipsychotic drugs, such as olanzapine, may slow progressive changes in brain structure in patients with schizophrenia. To investigate the possible neural basis of this effect, we sought to determine whether treatment with olanzapine would inhibit the loss of hippocampal neurons associated with the administration of the excitotoxin, kainic acid, in neonatal rats. At post-natal day 7 (P7), rats were exposed to kainic acid via intracerebroventricular administration. Neuronal loss within the CA2 and CA3 subfields of the hippocampus and neurogenesis within the dentate gyrus of the hippocampus were then assessed at P14 by Fluoro-Jade B and BrdU labeling, respectively. Daily doses of olanzapine (2, 6, or 12 mg/day), haloperidol (1.2 mg/kg), melatonin (10 mg/kg), or saline were administered between P7 and P14. Melatonin is an anti-oxidant drug and was included in this study as a positive control, since it has been observed to have neuroprotective effects in a variety of animal models. The highest dose of olanzapine and melatonin, but not haloperidol, ameliorated the hippocampal neuronal loss triggered by kainic acid administration. However, drug administration did not have a significant effect on the rate of neurogenesis. These results suggest that olanzapine has neuroprotective effects in a rat model of neurodevelopmental insult, and may be relevant to the observed effects of atypical antipsychotic drugs on brain structure in patients with schizophrenia.
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PMID:Neuroprotective effects of olanzapine in a rat model of neurodevelopmental injury. 1652 22

Melatonin (N-acetyl-5-methoxytryptamine) is a molecule known to be produced in multiple cells and organs. It acts at the level of the biological clock, the suprachiasmatic nuclei, to modulate their activity, thereby influencing circadian rhythms, and also sleep processes. The clinical application of melatonin in the treatment of human mental disorders is still in its infancy. Until now, melatonin only has been used in psychiatry because of its hypnotic, resynchronizing and antioxidant actions. In this review, we hypothesized that melatonin might play an important role as an adjuvant therapy, in mental disturbances, due to other properties including its anti-inflammatory, antinociceptive, anxiolytic, drug detoxification properties, protective actions against osteoporosis, etc. Complex interactions occur between the brain and the immune system and currently is accepted that psychological and psychiatric illness can compromise immune and hormonal functions. Altered psychological states often influence the susceptibility of an individual to illness or modify the course of the illness and its prognosis. The present review discusses on the advantages of the co-treatment with melatonin and recent patents in three major psychiatric disorders: depression, bipolar syndrome and schizophrenia. The findings suggest new vistas in both the pathophysiology and the pharmacology of mental disorders.
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PMID:The role of melatonin in the immuno-neuro-psychology of mental disorders. 1914 15

Haloperidol a typical antipsychotic commonly used in the treatment of schizophrenia causes neuronal damage and extrapiramidal symptoms after several years of treatment. These symptoms have been associated with increased levels of oxidative stress. Reactive oxygen species produce cytoskeletal collapse and an excessive phosphorylation of tau, a microtubule-associated protein that plays a key role in microtubule stabilization, and in growth cone and neurite formation, which are cytoskeletal phenotypes that participate in neurodevelopment. Thus, we hypothesized that haloperidol produces neurocytoskeletal disorganization by increasing free radicals and tau hyperphosphorylation, and consequently, the loss of neurodevelopmental cytoskeletal phenotypes, neurites and growth cones. The purpose of this work was the characterization of neuronal cytoskeletal changes caused by haloperidol in neuroblastoma N1E-115 cells. We also studied the mechanisms by which haloperidol causes cytoskeletal changes. The results showed that haloperidol at 100microM caused a complete cytoskeleton collapse in the majority of the cells. Melatonin, a free radical scavenger, blocks tau hyperphosphorylation, and microtubule disorganization caused by haloperidol in a dose-response mode. Additionally, the indole blocks lipoperoxide formation in haloperidol treated cells. The results indicate that free radicals and tau hyperphosphorylation produced by haloperidol caused a cytoskeletal collapse and the lost of growth cones and neurites. These effects were blocked by melatonin. Data suggest that extrapiramidal symptoms in schizophrenic patients can be produced by cytoskeletal disorganization during adult brain neurodevelopment after prolonged haloperidol treatment that can be prevented by melatonin.
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PMID:Haloperidol causes cytoskeletal collapse in N1E-115 cells through tau hyperphosphorylation induced by oxidative stress: Implications for neurodevelopment. 2062 Oct 83

This paper reviews melatonin as an overlooked factor in the developmental etiology and maintenance of schizophrenia; the neuroimmune and oxidative pathophysiology of schizophrenia; specific symptoms in schizophrenia, including sleep disturbance; circadian rhythms; and side effects of antipsychotics, including tardive dyskinesia and metabolic syndrome. Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as sources for this review using keywords: schizophrenia, psychosis, tardive dyskinesia, antipsychotics, metabolic syndrome, drug side effects and melatonin. Articles were selected on the basis of relevance to the etiology, course and treatment of schizophrenia. Melatonin levels and melatonin circadian rhythm are significantly decreased in schizophrenic patients. The adjunctive use of melatonin in schizophrenia may augment the efficacy of antipsychotics through its anti-inflammatory and antioxidative effects. Further, melatonin would be expected to improve sleep disorders in schizophrenia and side effects of anti-psychotics, such as tardive dyskinesia, metaboilic syndrome and hypertension. It is proposed that melatonin also impacts on the tryptophan catabolic pathway via its effect on stress response and cortisol secretion, thereby impacting on cortex associated cognition, amygdala associated affect and striatal motivational processing. The secretion of melatonin is decreased in schizophrenia, contributing to its etiology, pathophysiology and management. Melatonin is likely to have impacts on the metabolic side effects of anti-psychotics that contribute to subsequent decreases in life-expectancy.
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PMID:Melatonin: an overlooked factor in schizophrenia and in the inhibition of anti-psychotic side effects. 2252 98

Although melatonin has been implicated in several neurophysiological systems, data on the relationship of melatonin with psychosis such as schizophrenia are limited and contradictory. Chronic effects of melatonin on sensorimotor gating deficits have also not been investigated yet. We investigated the neurobehavioral effects of chronic administration of melatonin in pinealectomized (Px) and ovariectomized (Ovx) rats. Px or Ovx or both operations were carried out together to the rats. The control group of rats was sham operated. A sham ovariectomy was carried out to Px rats, and vice versa. Fifth month later, melatonin (5mg/kg) or vehicle was injected to rats for 28 days. Then, prepulse inhibition (PPI) of acoustic startle reflex, startle amplitude and startle reflex latency was measured. Locomotor activity, accelerod performance measurements, novel object recognition and passive avoidance tests were also evaluated. Px and Px+Ovx rats had impaired PPI compared to control rats. Melatonin reversed the impairments of PPI induced by Px or Px+Ovx. While melatonin treatment had no effect on locomotor activity of control rats, it significantly increased the locomotor activity of Px and Px+Ovx rats. Melatonin treatment (5mg/kg/day, 28 days) reversed the locomotor hyperactivity caused by Ovx. Accelerod performance, passive avoidance, and object recognition responses of Px, Ovx or Px+Ovx rats were not different from the control group. Our results indicate that chronic melatonin deficiency by reason of Px results in impairment of PPI reflex and replacement of melatonin exerts beneficial effects on the impaired PPI reflex in Px and Ovx rats. Thus, melatonin may be useful in the treatment of some disorders characterized by sensorimotor gating deficits such as schizophrenia.
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PMID:Chronic melatonin treatment reverses disruption of prepulse inhibition in pinealectomized and pinealectomized-plus-ovariectomized rats. 2307 52

Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia's biological etiology is multifactorial and is still under investigation. Melatonin has been involved in schizophrenia since the first decades of the twentieth century. Research into melatonin regarding schizophrenia has followed two different approaches. The first approach is related to the use of melatonin as a biological marker. The second approach deals with the clinical applications of melatonin as a drug treatment. In this paper, both aspects of melatonin application are reviewed. Its clinical use in schizophrenia is emphasized.
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PMID:Role of melatonin in schizophrenia. 2369 62

Prepulse inhibition of the startle reflex (PPI) is an operational measure of sensorimotor gating, which is demonstrated to be impaired in patients with schizophrenia. In addition, a disruption of the circadian rhythm together with blunted melatonin secretion is regularly found in patients with schizophrenia and it is theorized that these may contribute to their attentional deficits. The aim of this study was to assess the effects of acute melatonin on healthy human sensorimotor gating. Twenty-one healthy male volunteers were administered melatonin or placebo after which their levels of PPI were assessed. Melatonin significantly reduced startle magnitude and ratings of alertness, but did not influence PPI, nor sensitization and habituation. However, when taking baseline scores in consideration, melatonin significantly increased PPI in low scoring individuals while significantly decreasing it in high scoring individuals in low intensity prepulse trialtypes only. In addition, subjective ratings of alertness correlated with PPI. The results suggest that melatonin has only minor influences on sensorimotor gating, habituation and sensitization of the startle reflex of healthy males. The data do indicate a relationship between alertness and PPI. Further research examining the effects of melatonin on these processes in patients with schizophrenia is warranted.
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PMID:Effects of melatonin on prepulse inhibition, habituation and sensitization of the human startle reflex in healthy volunteers. 2461 47

Overweight and obesity are associated with significant morbidity and mortality. This is a known problem among individuals with psychiatric illness, which may be partly due to the adverse metabolic effects of certain psychotropic drugs. Melatonin, liraglutide, and naltrexone/bupropion are examples of drugs with different mechanisms of action that have favorable effects on obesity or medication-related weight gain. Melatonin is appropriate to consider for any patient who will be started on a psychotropic drug that is potentially associated with weight gain or other adverse metabolic effects. Liraglutide should also be considered appropriate for use in overweight or obese psychiatric patients, including those with medication-associated weight gain. The use of naltrexone/bupropion may be problematic in patients with bipolar disorder or schizophrenia because of the potential adverse effects of the bupropion component of the combination. All three drugs deserve further dedicated studies in psychiatric patient populations.
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PMID:Melatonin, Liraglutide, and Naltrexone/Bupropion for the Treatment of Obesity and Medication-Related Weight Gain. 2609 46


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