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)

Antidepressant drugs have in common a delayed onset of clinical efficacy. In rats, long-term, daily administration of four different types of clinically effective antidepressant drugs results in decreased corticotropin releasing hormone (CRH) mRNA expression levels in the hypothalamic paraventricular nucleus (PVN). Because a subpopulation of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (Arc) projects to the PVN, we measured NPY and POMC mRNA expression in the Arc using in situ hybridization histochemistry at several time points following daily administration of four different antidepressant drugs. After 14 and 56 days of imipramine treatment, Arc NPY mRNA levels are decreased to 85% and 75% of control levels, but are unchanged compared to control after one or five days of treatment. Arc POMC mRNA levels are unchanged compared to controls at 1, 5, 14, or 56 days following imipramine treatment. Unlike after imipramine, Arc NPY and POMC mRNA levels are increased significantly to 134-172% of control following 56-day treatment with the antidepressant drugs fluoxetine, phenelzine, or idazoxan. The divergent effects of imipramine vs the other 3 antidepressant drugs on Arc NPY mRNA expression are similar to the pattern of changes in tyrosine hydroxylase (TH) mRNA expression levels in the locus coeruleus (LC) using the same experimental paradigm, but are different from the unidirectional depressive effects of all four drugs on CRH mRNA expression in the PVN. Thus, the Arc NPY and LC noradrenergic systems may act coordinately in mediating antidepressant effects. The present data are consistent with the delayed onset of clinical efficacy for antidepressant drugs, and suggest that Arc NPY and POMC neurotransmitter systems play a role in the pathophysiology of depression.
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PMID:Effects of long-term treatment with antidepressant drugs on proopiomelanocortin and neuropeptide Y mRNA expression in the hypothalamic arcuate nucleus of rats. 873 33

Bifemelane hydrochloride (BH) is widely employed in Japan in the treatment of cerebral infarction patients with depressive symptoms and its antidepressant action is considered to be caused by the normalizing effects of neurotransmitters. The relationship between the normalizing effects of neurotransmitters of BH and the depressive state of patients with cerebral infarction was examined. BH 150 mg/day was administered for three months to 13 cerebral infarction patients with depressive state. We measured the plasma neuropeptide Y (NPY), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and 5-hydroxy-indole acetic acid (5-HIAA), and assessed the depressive symptoms using the 21-item Hamilton's Rating Scale for Depression (HRSD) before and after administration of BH. After treatment, the plasma NPY concentration was significantly increased, the plasma MHPG concentration and total score of HRSD were significantly decreased, and the plasma 5-HIAA concentration showed no changes. These findings suggest that the antidepressant effect of BH is caused by the normalizing effects of NPY and noradrenalinergic neurons.
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PMID:Effects of bifemelane hydrochloride on plasma neuropeptide Y, 3-methoxy-4-hydroxyphenylethylene glycol and 5-hydroxy-indole acetic acid concentrations in patients with cerebral infarction. 884 47

Since its discovery in 1982, neuropeptide Y (NPY) has been shown to have numerous effects mediated by a growing number of NPY receptors in both the CNS and peripheral nervous system. Perhaps best appreciated is the role of NPY in the control of systemic blood pressure, together with its effects on feeding, anxiety and memory. However, recent evidence increasingly supports an important role for NPY in mediating analgesia and hyperalgesia by distinct central and peripheral mechanisms. In this review we concentrate on this important aspect of NPY pharmacology and consider mechanisms controlling the expression of NPY and its receptors. In addition, we also present the more recent data describing the other possible roles for NPY-NPY agonists and antagonists may be useful in the treatment of conditions as varied as anorexia, epilepsy, anxiety, depression, hypertension and heart failure.
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PMID:The therapeutic potential of neuropeptide Y. Analgesic, anxiolytic and antihypertensive. 887 28

It has been suggested that neuropeptide Y (NPY) is involved in the pathophysiology of depression. Plasma peptide-rich fraction from patients with major depressive disorder and control subjects was eluted with high performance liquid chromatography (HPLC), followed by radioimmunoassay of NPY. The screening patterns of the NPY-like immunoreactivity in 50 fractions eluted by HPLC from the plasma peptide-rich fraction were different between the two groups. The values of NPY in the 16 controls and the 14 patients were 427 +/- 38 and 310 +/- 27 fmol/ml plasma (P < 0.05), respectively. These results suggest that impaired metabolism of plasma NPY and the reduced plasma NPY in patients with major depressive disorder could be involved in the pathogenesis or pathophysiology of major depressive disorder.
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PMID:Plasma neuropeptide Y in patients with major depressive disorder. 889 91

In vitro processing of neuropeptide Y (NPY) in cerebrospinal fluid (CSF) of patients with depression was monitored by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Single peptide bonds in NPY were cleaved to yield N- or C-terminal fragments. Multiple cleavage to form internal peptides was unimportant. Degradation rates varied between individuals, whereas the product distributions were fairly constant. Other peptides did not evidence such proteolysis. MALDI-TOF MS will facilitate extensive investigations of NPY processing that could provide the basis for clinical assays and illuminate the pathophysiology related to depression.
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PMID:Novel neuropeptide Y processing in human cerebrospinal fluid from depressed patients. 895 43

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common types of progressive neurodegenerative disorder in our catchment area. The distribution of cortical degeneration in FTD is mainly the reverse of that in AD, while there are both differences and similarities in the clinical characteristics. Somatostatin and neuropeptide Y (NPY) are neuropeptides with a widespread distribution in the human cerebral cortex. Somatostatin is involved in the regulation of hormone release from the anterior pituitary and may act as a neurotransmitter-modulator. NPY is a potent anxiolytic neuropeptide. Somatostatin and NPY coexist in the cerebral cortex, basal ganglia and in amygdaloid complexes. The present study of AD (n = 34) and FTD (n = 22) analyses the cerebrospinal-fluid (CSF) levels of somatostatin-like immunoreactivity and NPY-like immunoreactivity and correlates their levels to 54 different clinical items, such as restlessness, anxiety, irritability and depression. The CSF levels of the two neuropeptides somatostatin and NPY were significantly correlated in FTD (p < 0.02), but not in AD. Several significant correlations to the clinical signs were found: in AD disorientation and dyspraxia, and in FTD agitation, irritability and restlessness. Somatostatin showed a significant negative correlation with severity of dementia in AD (p < 0.013).
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PMID:Somatostatin and neuropeptide Y in cerebrospinal fluid: correlations with severity of disease and clinical signs in Alzheimer's disease and frontotemporal dementia. 921 68

Despite the increase in body fat and obesity that occurs with aging, there is a linear decrease in food intake over the life span. This conundrum is explained by decreased physical activity and altered metabolism with aging. Thus, older persons fail to adequately regulate food intake and develop a physiologic anorexia of aging. This physiologic anorexia depends not only on decreased hedonic qualities of feeding with aging (an area that remains controversial) but also on altered hormonal and neurotransmitter regulation of food intake. Findings in older animals and humans have provided clues to the causes of the anorexia of aging. An increase in circulating concentrations of the satiating hormone, cholecystokinin, occurs with aging in humans. In addition, animal studies suggest a decrease in the opioid (dynorphin) feeding drive and possibly in neuropeptide Y and nitric oxide. The physiologic anorexia of aging puts older persons at high risk for developing protein-energy malnutrition when they develop either psychologic or physical disease processes. Despite its high prevalence, however, protein-energy malnutrition in older persons is rarely recognized and even more rarely treated appropriately. Screening tools for the early detection of protein-energy malnutrition in older persons have been developed. Multiple treatable causes of pathologic anorexia have been identified. There is increasing awareness of the importance of depression as a cause of severe weight loss in older persons. Approaches to the management of anorexia and weight loss in older persons are reviewed. Although many drugs exist that can enhance appetite, none of these are ideal for use in older persons currently.
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PMID:Anorexia of aging: physiologic and pathologic. 973 60

Results from preclinical studies have validated the participation of neuropeptides in sleep regulation. In recent human and clinical studies it has been shown that peripheral administration of various peptides results in specific changes in the sleep electroencephalogram in humans. Furthermore, it has been demonstrated that certain peptides are common regulators of the electrophysiological and neuroendocrine components of sleep. It is now well established that the balance between the neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) plays a key role in normal and pathological sleep regulation. In young normal subjects, GHRH stimulates slow-wave sleep and growth hormone secretion but inhibits cortisol release, whereas CRH has the opposite effect. During normal aging and during acute depression, the GHRH:CRH ratio is changed in favor of CRH, resulting in disturbances in sleep endocrine activity. In addition to GHRH, galanin, growth hormone-releasing peptide, and neuropeptide Y also promote sleep, unlike ACTH(4-9), which disturbs sleep. In elderly subjects, sleep deteriorates after acute administration of somatostatin but improves after chronic treatment with vasopressin. Vasoactive intestinal polypeptide decelerates the non-rapid eye movement-rapid eye movement cycle and advances the occurrence of the cortisol nadir. The impact of delta sleep-inducing peptide, cholecystokinin, and thyrotropin-releasing hormone on human sleep regulation is not yet clear. This paper reviews recent work investigating the influence of these various neuropeptides on sleep.
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PMID:Neuropeptides and human sleep. 945 70

Epidemiological and clinical data indicate high comorbidity between depression and drug dependence that may reflect an attempt to self-medicate with drugs of abuse. The present review examines whether these two psychiatric disorders are related by attempting to identify similarities in the neurobiology of depression and drug dependence. Emphasis is put on the neuromechanisms that may mediate specific core symptoms of both disorders that reflect alterations in reward and motivational processes. First, the epidemiological and clinical data on the comorbidity of the two disorders are reviewed briefly. Then, the neuroadaptations associated with psychomotor stimulant, opiate, ethanol, nicotine, and benzodiazepine dependence in animals are reviewed. Finally, the neurotransmitter systems whose function appears to be altered in depression (i.e., serotonin, norepinephrine, acetylcholine, dopamine, gamma-aminobutyric acid, corticotropin releasing factor, neuropeptide Y, and somatostatin), as revealed primarily by animal studies, are discussed. It is concluded that drug dependence and depression may be associated with alterations in some of the same neurotransmitter systems and, in particular, with alterations of neurotransmitter function in limbic-related brain structures. Thus, these two psychiatric disorders may be linked by some shared neurobiology. Nevertheless, it remains unclear whether drug abuse and depression are different symptomatic expressions of the same preexisting neurobiological abnormalities, or whether repeated drug abuse leads to the abnormalities mediating depression (i.e., drug-induced depressions). The hypothesis of self-medication of non-drug- and drug-induced depressions with drugs of abuse is also discussed as a potentially important explanatory concept in understanding the observed clinical comorbidity of these two psychiatric disorders.
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PMID:Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. 947 Nov 14

Administration of hormones to humans and animals results in specific effects on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. Studies with pulsatile administration of various neuropeptides in young and old normal controls and in patients with depression suggest they play a key role in sleep-endocrine regulation. Growth hormone (GH)-releasing hormone (GHRH) stimulates GH and slow wave sleep (SWS) and inhibits cortisol, whereas corticotropin-releasing hormone (CRH) exerts opposite effects. Changes in the GHRH:CRH ratio contribute to sleep-endocrine aberrations during normal ageing and acute depression. In addition, galanin and neuropeptide Y promote sleep, whereas, in the elderly, somatostatin impairs sleep. The rapid eye movement (REM)-nonREM cycle is modulated by vasoactive intestinal polypeptide. Cortisol stimulates SWS and GH, probably by feedback inhibition of CRH. Neuroactive steroids exert specific effects on the sleep EEG, which can be explained by gamma-aminobutyric acid(A) receptor modulation.
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PMID:Effects of hormones on sleep. 955 Jan 12


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