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)

In times of stress the hypothalamic-pituitary-adrenal (HPA) axis is activated and releases two neurohormones, corticotropin-releasing hormone (Crh) and arginine vasopressin (Avp), to synergistically stimulate the secretion of adrenocorticotropin hormone (ACTH) from the anterior pituitary, culminating in a rise in circulating glucocorticoids. Avp mediates its actions at the Avp V1b receptor (Avpr1b) present on pituitary corticotropes. Dysregulation of the stress response is associated with the pathophysiology of depression and a major treatment involves increasing the availability of monamines at the synaptic cleft. Acute administration of selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) has previously been shown to activate the HPA axis. The present study was undertaken to evaluate the involvement of the Avpr1b in the HPA axis response to acute SC administration of an SSRI (fluoxetine 10mg/kg) and a TCA (desipramine 10mg/kg). We measured plasma ACTH and corticosterone (CORT) levels and neuropeptide mRNA expression in the hypothalamic paraventricular nucleus (PVN) of Avpr1b knockout (KO) mice and wild-type controls. Fluoxetine and desipramine administration significantly attenuated plasma ACTH and CORT levels in male and female Avpr1b KO mice when compared to their wild-type counterparts. Avp, oxytocin (Oxt) and Crh mRNA expression in the PVN did not change in fluoxetine-treated male Avpr1b KO or wild-type mice. In contrast, fluoxetine treatment increased PVN Avp mRNA levels in female Avpr1b wild type but not KO animals. PVN Oxt mRNA levels increased in fluoxetine-treated female mice of both genotypes. The data suggests that the Avpr1b is required to drive the HPA axis response to acute antidepressant treatment and provides further evidence of a sexual dichotomy in the regulation of PVN Avp/Oxt gene expression following antidepressant administration.
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PMID:The role of the arginine vasopressin Avp1b receptor in the acute neuroendocrine action of antidepressants. 1824 68

Despite extensive research on the involvement of oxytocin (OT) in mammalian bonding, less is known about its role in human social affiliation across the life cycle. Forty-five romantically unattached young adults participated. Plasma oxytocin and salivary cortisol were assessed using enzyme immuno-assay, and self-report measures of bonding, attachment, anxiety, and depression were collected. Oxytocin was associated with bonding to own parents and inversely related to psychological distress, particularly depressive symptoms. Cortisol was related to attachment anxiety. Regression analysis indicated that the adult's representations of bonding to parents predicted OT levels above and beyond cortisol, psychological distress, and attachment. Findings are consistent with antistress models of oxytocin and suggest that oxytocin may play a role in bonding-related cognitions across the life span.
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PMID:Oxytocin and cortisol in romantically unattached young adults: associations with bonding and psychological distress. 1826 3

Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRF expression, including (1) corticosteroid receptors and their chaperones, heat shock proteins 70 and 90, (2) sex hormone receptors, (3) CRF receptors 1 (CRFR1) and 2, (4) cytokines interleukin 1-beta and tumor necrosis factor-alpha, (5) neuropeptides and receptors, vasopressin (AVP), AVP receptor 1a (AVPR1A) and oxytocin and (6) transcription factor cAMP-response element-binding protein. We hypothesized that, in depression, the transcript levels of those genes that are involved in the activation of the hypothalamo-pituitary-adrenal (HPA) axis are upregulated, whereas the transcript levels of the genes involved in the inhibition of the HPA axis are downregulated. We performed laser microdissection and real-time PCR in the PVN and as a control in the supraoptic nucleus. Snap-frozen post-mortem hypothalami of seven depressed and seven matched controls were used. We found significantly increased CRF mRNA levels in the PVN of the depressed patients. This was accompanied by a significantly increased expression of four genes that are involved in the activation of CRF neurons, that is, CRFR1, estrogen receptor-alpha, AVPR1A and mineralocorticoid receptor, while the expression of the androgen receptor mRNA involved in the inhibition of CRF neurons was decreased significantly. These findings raise the possibility that a disturbed balance in the production of receptors may contribute to the activation of the HPA axis in depression.
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PMID:Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances. 1860 75

In addition to various reproductive stimuli, the neuropeptide oxytocin (OXT) is released both from the neurohypophysial terminal into the blood stream and within distinct brain regions in response to stressful or social stimuli. Brain OXT receptor-mediated actions were shown to be significantly involved in the regulation of a variety of behaviours. Here, complementary methodological approaches are discussed which were utilised to reveal, for example, anxiolytic and anti-stress effects of OXT, both in females and in males, effects that were localised within the central amygdala and the hypothalamic paraventricular nucleus. Also, in male rats, activation of the brain OXT system is essential for the regulation of sexual behaviour, and increased OXT system activity during mating is directly linked to an attenuated anxiety-related behaviour. Moreover, in late pregnancy and during lactation, central OXT is involved in the establishment and fine-tuned maintenance of maternal care and maternal aggression. In monogamous prairie voles, brain OXT is important for mating-induced pair bonding, especially in females. Another example of behavioural actions of intracerebral OXT is the promotion of social memory processes and recognition of con-specifics, as revealed in rats, mice, sheep and voles. Experimental evidence suggests that, in humans, brain OXT exerts similar behavioural effects. Thus, the brain OXT system seems to be a potential target for the development of therapeutics to treat anxiety- and depression-related diseases or abnormal social behaviours including autism.
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PMID:Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. 1860 10

Glutamate exerts its effects through binding and activation of two classes of specific receptors: ionotropic (iGluRs) and metabotropic (mGluRs). Group I mGluR includes mGluR1 and mGluR5 subtypes, group II includes mGluR2 and mGluR3 subtypes and group III includes the subtypes mGluR 4, 6, 7 and 8. Glutamate and its receptors are found in all key hypothalamic areas critically involved in reproduction and neuroendocrine function. To date, considerable data support an important role for iGluRs in the control of neuroendocrine function; however, the role of mGluRs as regulators of hypothalamic-pituitary function has not been clearly elucidated. mGluRs could be exerting a fine tune on the release of hypothalamic factors that regulate hormone release such as Substance P, GABA, alpha-MSH and CRH. Group II mGluR exert a direct inhibitory effect on anterior pituitary prolactin and GH secretion. Moreover, some group II mGluR agonists, like LY 354,740 and LY 379,268, can modulate PRL secretion from the anterior pituitary through their actions as dopamine receptor agonists. Evidence suggests a role for group III mGluR subtypes in stress-related behavioral disorders. Several reports indicate that selective ligands for mGluR subtypes have potential for the treatment of a wide variety of neurological and psychiatric disorders, including depression, anxiety disorders, schizophrenia, epilepsy and Alzheimer's disease among others. Since converging lines of evidence suggest a role for mGluRs subtypes in neuroendocrine regulation of hormone secretion, mGluRs neuroendocrine actions must be taken in consideration to insure proper treatment of these diseases. Moreover, discovery of selective agonists provides an opportunity to investigate the physiological role of mGluR subtypes and to directly test the neuroendocrine actions of mGluRs. Finally, mGluRs selective agonists may have an impact in the treatment of conditions involving chronic stress, such as depression and anxiety disorders, since they regulate neuroendocrine stress circuits involving the HPA axis and stress-sensitive hormones such as oxytocin and prolactin. This review aims to provide a survey of our current understanding of the effects of mGluR activation on neuroendocrine function.
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PMID:Role of metabotropic glutamate receptors in the control of neuroendocrine function. 1861 55

Previous studies indicated that oxytocin plays an important role in human trust, which is impaired in patients with severe mental disorders. In this study, we measured plasma oxytocin levels in patients with schizophrenia (n=50) and in healthy controls (n=50) after neutral and trust-related interpersonal interactions. Trust-related interactions were associated with increased oxytocin levels in controls. This effect was absent in patients with schizophrenia. Low oxytocin levels measured after trust-related interactions significantly predicted the negative symptoms of schizophrenia but were not related to positive symptoms, depression, anxiety, and neuropsychological functions. These results suggest that decreased trust-related oxytocin release is related to the negative symptoms and may be associated with social withdrawal, isolation, and flattened affect in schizophrenia.
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PMID:Sharing secrets: oxytocin and trust in schizophrenia. 1867 Nov 68

Both oxytocin and serotonin modulate affiliative responses to partners and offspring. Animal studies suggest a crucial role of oxytocin in mammalian parturition and lactation but also in parenting and social interactions with offspring. The serotonergic system may also be important through its influence on mood and the release of oxytocin. We examined the role of serotonin transporter (5-HTT) and oxytocin receptor (OXTR) genes in explaining differences in sensitive parenting in a community sample of 159 Caucasian, middle-class mothers with their 2-year-old toddlers at risk for externalizing behavior problems, taking into account maternal educational level, maternal depression and the quality of the marital relationship. Independent genetic effects of 5-HTTLPR SCL6A4 and OXTR rs53576 on observed maternal sensitivity were found. Controlling for differences in maternal education, depression and marital discord, parents with the possibly less efficient variants of the serotonergic (5-HTT ss) and oxytonergic (AA/AG) system genes showed lower levels of sensitive responsiveness to their toddlers. Two-way and three-way interactions with marital discord or depression were not significant. This first study on the role of both OXTR and 5-HTT genes in human parenting points to molecular genetic differences that may be implicated in the production of oxytocin explaining differences in sensitive parenting.
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PMID:Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. 1901 99

The oxytocin receptor has been implicated in the regulation of reproductive physiology as well as social and emotional behaviors. The neurochemical mechanisms by which oxytocin receptor modulates social and emotional behavior remains elusive, in part because of a lack of sensitive and selective antibodies for cellular localization. To more precisely characterize oxytocin receptor-expressing neurons within the brain, we generated an oxytocin receptor-reporter mouse in which part of the oxytocin receptor gene was replaced with Venus cDNA (a variant of yellow fluorescent protein). Examination of the Venus expression revealed that, in the raphe nuclei, about one-half of tryptophan hydroxylase-immunoreactive neurons were positive for Venus, suggesting a potential role for oxytocin in the modulation of serotonin release. Oxytocin infusion facilitated serotonin release within the median raphe nucleus and reduced anxiety-related behavior. Infusion of a 5-HT(2A/2C) receptor antagonist blocked the anxiolytic effect of oxytocin, suggesting that oxytocin receptor activation in serotonergic neurons mediates the anxiolytic effects of oxytocin. This is the first demonstration that oxytocin may regulate serotonin release and exert anxiolytic effects via direct activation of oxytocin receptor expressed in serotonergic neurons of the raphe nuclei. These results also have important implications for psychiatric disorders such as autism and depression in which both the oxytocin and serotonin systems have been implicated.
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PMID:Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. 1922 79

Arginine vasopressin (AVP) and oxytocin (OXT), produced in the hypothalamic paraventricular (PVN) and supraoptic nucleus (SON), are considered to be involved in the pathophysiology of major depressive disorder (MDD). The objective of this study was to determine, for the first time, the relationship between AVP and OXT gene expression and depressive state in Alzheimer's disease (AD). Post-mortem brain tissue was obtained from six control subjects, and from a prospectively studied cohort of 23 AD patients, using the DSM-IIIR and the Cornell Scale for Depression in Dementia to determine depression diagnosis and severity. The amount of AVP and OXT mRNA was determined by in situ hybridisation. AD patients did not differ from controls with respect to the amount of AVP or OXT mRNA in the PVN or SON. Also, no differences were found between depressed and nondepressed AD patients and no relationship was found between the depression severity and AVP or OXT mRNA expression. The results indicate that AVP and OXT gene expression in the PVN and SON is unchanged in depressed AD patients compared to nondepressed AD patients. This is in contrast with the enhanced AVP gene expression in MDD, suggesting a difference in pathophysiology between MDD and depression in AD.
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PMID:Hypothalamic vasopressin and oxytocin mRNA expression in relation to depressive state in Alzheimer's disease: a difference with major depressive disorder. 1950 Feb 16

Much evidence of an association between specific attachment styles and depression prompted us to investigate, in depressive disorders, the potential role of polymorphisms within the gene encoding the receptor of the main neurohormone involved in attachment processes, oxytocin. For this purpose, two single nucleotide polymorphisms (SNPs), 6930G>A (rs53576) and 9073G>A (rs2254298), within the oxytocin receptor gene (OXTR), were studied in a cohort of 185 patients with major depression (50.3%) or bipolar I or II disorders (49.7%) and 192 matched healthy controls. A positive association between the GG genotype of OXTR SNPs (6930G>A or 9073G>A) and unipolar depression was demonstrated. In this group, GG individuals showed high scores on Attachment Style Questionnaire factors that have been previously associated with depression. Moreover, the GG genotype was also associated with high levels of adult separation anxiety. These findings support the involvement of the oxytocinergic system in the mechanisms that underlie depression and specific adult attachment styles.
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PMID:Oxytocin receptor polymorphisms and adult attachment style in patients with depression. 1951 97


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