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)

One hundred and ten patients with Research Diagnostic Criteria (RDC) diagnoses of major depressive disorders were assessed for present or recent suicidal ideation and behavior and for suicidal acts earlier in life before current depression using the Schedule for Affective Disorders and Schizophrenia (SADS). Suicidal scores were correlated uni- and bivariately with levels of CSF monoamine metabolites (HVA, 5HIAA, MHPG), urinary MHPG, the proportion post-/predexamethasone plasma cortisol at 1100 h, and platelet MAO activity (all standardized to same sex, age, height and weight). Results indicate that all 3 monoamine metabolites and their interactions are involved in various aspects of suicidality, at least in unipolar patients. MHPG and 5HIAA (both low or both high) were involved in current or recent suicidal ideation, and low HVA was mainly associated with past potential lethality of suicidal acts. Current hypercortisolism was found in patients that earlier in life had tried to commit dangerous suicides. Bipolar patients (depressives with a history of manic or hypomanic episodes) had earlier in life significantly more, and more dangerous, suicidal attempts than the unipolars.
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PMID:Life at risk: markers of suicidality in depression. 620 42

Measures of neuroendocrine function--plasma cortisol and its response to dexamethasone, and plasma thyroid-stimulating hormone (TSH) and its response to thyrotropin-releasing hormone (TRH)--were employed in 50 hospitalized male veteran psychiatric patients with diagnoses of unipolar or bipolar melancholia, secondary depression, or schizophrenia. Of 20 cases of unipolar melancholia, 17 (85%) exhibited hypercortisolism; 14 (70%) failed to suppress plasma cortisol after dexamethasone; and 4 (31%) of 13 tested had an abnormal TSH response to intravenous TRH. Two patients with secondary depression also exhibited hypercortisolism; no other patients evinced abnormal neuroendocrine test results. These measures were repeated in 14 unipolar depressed patients after a course of electroconvulsive therapy (ECT). Improvement in psychopathology was directly related to normalization of measures of hypothalamic-pituitary-adrenal (HPA) function. The TSH response to TRH was not systematically altered. After a followup period of 1 to 9 months, there was a good correlation between the measures of HPA function and the clinical outcome. These findings encourage further study of HPA function measures as outcome criteria for depressed patients receiving ECT.
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PMID:Neuroendocrine measures in psychiatric patients: course and outcome with ECT. 678 39

Combined exposures to maternal lead (Pb) and prenatal stress (PS) can act synergistically to enhance behavioral and neurochemical toxicity in offspring. Maternal Pb itself causes permanent dysfunction of the body's major stress system, the hypothalamic pituitary adrenal (HPA) axis. The current study sought to determine the potential involvement of altered negative glucocorticoid feedback as a mechanistic basis of the effects in rats of maternal Pb (0, 50 or 150 ppm in drinking water beginning 2 mo prior to breeding), prenatal stress (PS; restraint on gestational days 16-17) and combined maternal Pb+PS in 8 mo old male and female offspring. Corticosterone changes were measured over 24 h following an i.p. injection stress containing vehicle or 100 or 300 microg/kg (females) or 100 or 150 microg/kg (males) dexamethasone (DEX). Both Pb and PS prolonged the time course of corticosterone reduction following vehicle injection stress. Pb effects were non-monotonic, with a greater impact at 50 vs. 150 ppm, particularly in males, where further enhancement occurred with PS. In accord with these findings, the efficacy of DEX in suppressing corticosterone was reduced by Pb and Pb+PS in both genders, with Pb efficacy enhanced by PS in females, over the first 6 h post-administration. A marked prolongation of DEX effects was found in males. Thus, Pb, PS and Pb+PS, sometimes additively, produced hypercortisolism in both genders, followed by hypocortisolism in males, consistent with HPA axis dysfunction. These findings may provide a plausible unifying biological mechanism for the reported links between Pb exposure and stress-associated diseases and disorders mediated via the HPA axis, including obesity, hypertension, diabetes, anxiety, schizophrenia and depression. They also suggest broadening of Pb screening programs to pregnant women in high stress environments.
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PMID:Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: a potential biological unifying mechanism for their corresponding disease profiles. 1897 74

Approximately one third of patients diagnosed with schizophrenia do not achieve adequate symptom control with standard antipsychotic drugs (APs). Some of these may prove responsive to clozapine, but non-response to APs remains an important clinical problem and cause of increased health care costs. In a significant proportion of patients, schizophrenia is associated with natural and iatrogenic metabolic abnormalities (obesity, dyslipidaemia, impaired glucose tolerance or type 2 diabetes mellitus), hyperadrenalism and an exaggerated HPA response to stress, and chronic systemic inflammation. The endocannabinoid system (ECS) in the brain plays an important role in maintaining normal mental health. ECS modulates emotion, reward processing, sleep regulation, aversive memory extinction and HPA axis regulation. ECS overactivity contributes to visceral fat accumulation, insulin resistance and impaired energy expenditure. The cannabis plant synthesises a large number of pharmacologically active compounds unique to it known as phytocannabinoids. In contrast to the euphoric and pro-psychotic effects of delta-9-tetrahydrocannabinol (THC), certain non-intoxicating phytocannabinoids have emerged in pre-clinical and clinical models as potential APs. Since the likely mechanism of action does not rely upon dopamine D2 receptor antagonism, synergistic combinations with existing APs are plausible. The anti-inflammatory and immunomodulatory effects of the non-intoxicating phytocannabinoid cannabidiol (CBD) are well established and are summarised below. Preliminary data reviewed in this paper suggest that CBD in combination with a CB1 receptor neutral antagonist could not only augment the effects of standard APs but also target the metabolic, inflammatory and stress-related components of the schizophrenia phenotype.
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PMID:Cannabinoids and schizophrenia: therapeutic prospects. 2382 68