Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of different psychological stimuli on oxytocin (OT) and vasopressin (AVP) secretion are reviewed in animals and in humans. The secretion of neuropituitary hormones is also discussed in various psychiatric diseases such an anorexia nervosa, bipolar disorder, schizophrenia and obsessive-compulsive disorder. AVP and OT are secreted into the hypophyseal portal circulation by neurons which project from the paraventricular nucleus to the external zone of the median eminence. AVP and OT-containing neurons in the suprachiasmatic and paraventricular nuclei project to limbic areas, including the hippocampus, the subiculum, the ventral nucleus of the amygdala and the nucleus of the diagonal band. Specific AVP receptors which are pharmacologically different from the pressor and antidiuretic AVP receptors have been found in the anterior pituitary. OT receptors have been identified in a variety of forebrain sites. The neurohypophyseal secretion is regulated by the cholinergic muscarinic, histaminergic and beta-adrenergic systems. Stress alters the secretion of one or more of the hypothalamic factors which interact at the pituitary to increase the secretion of ACTH. AVP and OT have been shown to modulate the effect of Corticotropin-Releasing Factor (CRF) on ACTH secretion and appear to play a key role in mediating the ACTH response to stress. Although AVP is a relatively weak secretagogue for ACTH, it markedly potentiates the activity of CRF both in vitro and in vivo. The role of OT is more complex. In vitro, OT stimulates ACTH release at high doses whereas in human it inhibits ACTH secretion at low doses. The type of stressor appear to determine the relative importance of these secretatogues in ACTH response. Several recent studies indicate that psychological stressors display a similar degree of variety of secretagogue release patterns as was found earlier for physical stressors. A bewildering array of technique produces a bewildering array of conclusions. In rats, OT may be an important secretagogue during a novel stimulus, whereas the role for AVP is less clear. Indeed two studies out of ten suggest a stimulating role for AVP. In response to frustration and submission, OT and AVP are secreted. Regarding social isolation, results are difficult to interpret and the role of AVP could be species-dependent. In contrast plasma OT levels do not change. After restraint, ACTH release is primarily mediated by the active increase of OT and AVP does not appear to play a role. When restraint is associated with moderate levels of physical components and during immobilisation, all two secretagogs are involved in the ACTH response. With fear, ACTH response appears to be driven by OT. In humans, one study indicates that high emotionality women increase plasma OT in response to uncontrollable noise. Various neuroendocrine dysregulations have been observed in psychiatric disease. Either an increase or a decrease of the hypothalamic-pituitary-adrenal (HPA) function have been described in several illnesses. Effects of OT appear to be reciprocal to the effects of AVP. OT has been called the "amnestic" neuropeptide due to its capacity to attenuate memory consolidation and retrieval. AVP exhibits a central activating action on mood, memory and selective attention. Underweight patients with anorexia nervosa have abnormally high levels of centrally directed AVP and reduced OT levels. These modifications could enhance the retention of cognitive distortions of aversive consequences of eating. Patients with bipolar disorder show a biphasic secretion of AVP. Depressive episodes are associated with decreased vasopressinergic activity whereas manic episodes involve an increased release. AVP might be responsible for an increased catecholamine activity. In addition, lithium could act as an antagonist to AVP. In schizophrenic patients, studies using the apomorphine stimulation suggest increased oxytoninergic and decreased vasopressinergic functions. These findings are consistent with the beneficial role of AVP on schizophrenic symptoms noted in several trials. The increased OT could be responsible for "positive" symptomatology such as delusions and hallucinations. Obsessive compulsive disorder (OCD) includes a range of cognitive and behavioral disturbances that could be influenced by OT. In animals, several studies have emphasized the role of AVP in promoting repetitive grooming behaviors and maintaining conditioned response to aversive stimuli. In OCD patients, one study have reported that AVP/OT ratio was negatively correlated with symptom severity. However, an independent report found similar AVP concentrations in OC patients without a personal or family history of tic disorder and in normal subjects. Whether these modifications are only a consequence of the central disturbances or whether those peptides could participate in the pathogenesis of these affections remains to be elucidated.
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PMID:[Role of the neurohypophysis in psychological stress]. 1148 55

Schizophrenia is a complex and multifactorial disorder generally diagnosed in young adults at the time of the first psychotic episode of delusions and hallucinations. These positive symptoms can be controlled in most patients by currently-available antipsychotics. Conversely, they are poorly effective against concomitant neurocognitive dysfunction, deficits in social cognition and negative symptoms (NS), which strongly contribute to poor functional outcome. The precise notion of NS has evolved over the past century, with recent studies - underpinned by novel rating methods - suggesting two major sub-domains: "decreased emotional expression", incorporating blunted affect and poverty of speech, and "avolition", which embraces amotivation, asociality and "anhedonia" (inability to anticipate pleasure). Recent studies implicate a dysfunction of frontocortico-temporal networks in the aetiology of NS, together with a disruption of cortico-striatal circuits, though other structures are also involved, like the insular and parietal cortices, amygdala and thalamus. At the cellular level, a disruption of GABAergic-glutamatergic balance, dopaminergic signalling and, possibly, oxytocinergic and cannibinoidergic transmission may be involved. Several agents are currently under clinical investigation for the potentially improved control of NS, including oxytocin itself, N-Methyl-d-Aspartate receptor modulators and minocycline. Further, magnetic-electrical "stimulation" strategies to recruit cortical circuits and "cognitive-behavioural-psychosocial" therapies likewise hold promise. To acquire novel insights into the causes and treatment of NS, experimental study is crucial, and opportunities are emerging for improved genetic, pharmacological and developmental modelling, together with more refined readouts related to deficits in reward, sociality and "expression". The present article comprises an integrative overview of the above issues as a platform for this Special Issue of European Neuropsychopharmacology in which five clinical and five preclinical articles treat individual themes in greater detail. This Volume provides, then, a framework for progress in the understanding - and ultimately control - of the debilitating NS of schizophrenia.
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PMID:Negative symptoms of schizophrenia: clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. 2482 Feb 38

Schizophrenia is a chronic debilitating neuropsychiatric disorder estimated to affect 51 million people worldwide. Several symptom domains characterize schizophrenia, including negative symptoms, such as social withdrawal and anhedonia, cognitive impairments, such as disorganized thinking and impaired memory, and positive symptoms, such as hallucinations and delusions. While schizophrenia is a complex neuropsychiatric disorder with no single "cause," there is evidence that the oxytocin (Oxt) system may be dysregulated in some individuals. Further, treatment with intranasal Oxt reduces some of the heterogeneous symptoms associated with schizophrenia. Since Oxt is known for its modulatory effects on a variety of social and non-social behaviors, it is perhaps not surprising that it may contribute to some aspects of schizophrenia and could also be a useful therapeutic agent. In this review, we highlight what is known about Oxt's contributions to schizophrenia and schizophrenia-related behaviors and discuss its potential as a therapeutic agent.
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PMID:A Role for Oxytocin in the Etiology and Treatment of Schizophrenia. 2608 15

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry.
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PMID:Modern Clinical Research on LSD. 2844 22