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

CEE-03-310 is a selective dopamine D1-like receptor antagonist with no appreciable binding affinity for other receptors. Although originally developed by Novo Nordisk A/S as NNC-687 for the treatment of schizophrenia, the company changed its therapeutic focus in the mid-1990s and the full rights to CEE-03-310 and several related compounds were subsequently granted to CeNeS Pharmaceuticals in 1999. CeNeS is currently investigating the drug's potential in the treatment of insomnia and alcohol dependency [340965], [382293], [401496],[416026]. A phase II, double-blind, placebo-controlled trial of CEE-03-310 demonstrated a dose-dependent enhancement of NREM sleep at the beginning of the night without any effects on the quantity of REM sleep [410739].
 ...
PMID:CEE-03-310 CeNeS pharmaceuticals. 1202 61

Sleep disturbances have been associated with schizophrenia, and are an especially prominent feature during the prodrome preceding psychotic relapse. In this study, we examined the changes in sleep quality following withdrawal of antipsychotic treatment, as well as the predictive value of sleep disturbances on symptom exacerbation. One hundred twenty-two patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder underwent a 3-week medication wash-out prior to neuroimaging studies. Sleep quality was rated using items on the Hamilton Rating Scale for Depression (HAM-D), while symptom severity was measured using the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). Sleep quality deteriorated progressively following antipsychotic discontinuation. Total insomnia score prior to antipsychotic withdrawal had a significant effect on the severity of psychotic symptoms at the last weekly assessment, while baseline terminal insomnia had a significant effect on disorganized symptoms at the end of the medication-free period. These findings were independent of baseline symptom severity. Our findings suggest that schizophrenia patients with sleep disturbances are at a greater risk for worsening of positive symptoms after antipsychotic discontinuation. The implications of these findings in research and clinical settings are discussed.
 ...
PMID:Insomnia as a predictor for symptom worsening following antipsychotic withdrawal in schizophrenia. 1221 15

Alteration in the isoprenoid metabolites--digoxin, ubiquinone, and dolichol--have been reported in neuronal degeneration (Parkinson's disease), oncogenesis (central nervous system glioma), functional neuropsychiatric disorders (schizophrenia and epilepsy), and immune-mediated disorders (multiple sclerosis). The coexistence of these disorders has been documented in literature and a central dysfunction related to digoxin and the isoprenoid pathway may underlie all these disorders. A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome X, rheumatoid arthritis, and epilepsy has been described. The psychological behavioral patterns of the family were: creativity and high IQ, hypersexual behavior, reduced appetite and eating behavior, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less bonding and affectionate behavior, and left handedness/right hemispheric dominance. Digoxin, an endogenous Na(+)-K+ ATPase inhibitor secreted by the hypothalamus, was found to be elevated and red blood cell (RBC) membrane Na(+)-K+ ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine, resulting in increased levels of depolarizng tryptophan catabolites, serotonin, quinolinic acid, strychnine, and nicotine, and decreased levels of hyperpolarizing tyrosine catabolites, dopamine, noradrenaline, and morphine, contributing to membrane Na(+)-K+ ATPase inhibition in all the above disorders and the indexed family. Digoxin-induced membrane Na(+)-K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced Mg2+ levels, leading on to glutamate excitotoxicity, oncogene activation, and immune activation. Digoxin-induced altered Ca2+/Mg2+ ratios, reduced ubiquinone, and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure, and mitochondrial function, leading to the diverse disorders described above, including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/LH dominant and left-handed/RH dominant individuals. The left-handed/RH dominant individuals compared to right-handed/LH dominant individuals had elevated hydroxymethylglutarylcoenzyme A reductase activity, with increased serum digoxin and dolichol levels. The serum ubiquinone, serum Mg2+ and RBC Na(+)-K+ ATPase activity were reduced in left-handed/RH dominant individuals. The left-handed/RH dominant individuals compared to right-handed/LH dominant individuals had elevated levels of serum tryptophan, quinolinic acid, serotonin, nicotine, and strychnine. The levels of tyrosine, dopamine, noradrenaline, and morphine were low in left-handed/RH dominant compared to right-handed/LH dominant individuals. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and coordinate the functions of various cellular organelles.
 ...
PMID:Central role of hypothalamic digoxin in conscious perception, neuroimmunoendocrine integration, and coordination of cellular function: relation to hemispheric dominance. 1232 12

There is extensive evidence to implicate dysregulation of noradrenergic, serotonergic, and dopaminergic neurotransmission in the pathophysiology of mood disorders. The receptor profile for risperidone, an atypical antipsychotic with demonstrated efficacy in schizophrenia, is consistent with possible antidepressant activity. Specifically, risperidone is a potent antagonist of central 5-HT2A receptors, addressing symptoms such as insomnia, agitation, and weight loss and may indirectly enhance 5-HT1A-mediated neurotransmission. A search of the worldwide medical literature published through December 2000 revealed 24 publications pertinent to the clinical use of risperidone in the treatment of patients with depressive symptomatology. In schizophrenia, in which depression is a common comorbid condition, the results of eight randomized, blinded, and controlled trials consistently demonstrated that treatment with risperidone significantly reduced scores on various measures of depressive symptoms. Moreover, these effects were distinct from improvements in negative and positive symptoms. Antidepressant effects also were observed in two large meta-analyses of trials in patients with schizophrenia or schizoaffective disorder. Observations from uncontrolled studies and case reports of risperidone therapy of other psychiatric disorders were similarly suggestive of antidepressant activity. Collectively, the evidence we present in this review indicates that risperidone's therapeutic benefits in psychiatric medicine extend beyond potent and effective antipsychotic activity and may include effectiveness in treating depression and related affective disorders. Systematic studies are now needed to evaluate the utility of concomitant therapy with an atypical antipsychotic in psychotic, bipolar, and treatment-resistant depressive syndromes.
 ...
PMID:Risperidone: review of its therapeutic utility in depression. 1239 61

In the article, the author develops an analysis of external and intrapsychic factors related to adults' insomnia. First she undertakes a literature review to describe semiological, evolutive and etiological levels of insomnia. From a semiological point of view, it is usual to differenciate initial insomnia (associated to the first phase of sleeping), intermittent insomnia (related to frequent awakenings) and final insomnia (related to early morning awakenings). From an evolutive point of view, we can identify transitory insomnia (characterized by frequent awakenings) and chronic insomnia. On the other hand, we are allowed to distinguish organic insomnia (disorder where an organic cerebral injury is demonstrated or suspected) from insomnias related to psychiatric or somatic disease or idiopathic one. Then, the author makes a literary review to identify various insomnia causes and points out. Social factors: insomnia rates are higher by divorced, separated or widowed people. Percentages are higher when scholastic level is weak, domestic income is less then 915 O a month, or by unemployed people. Besides, sleep quality is deteriorated by ageing. Sleeping and waking rhythm is able to loose its synchronization. Complaints about insomnia occur far frequently from women than men. Environmental factors: working constraints increase sleep disorders. It is possible to make the same conclusion when we have to face overcharge of external events, deep intrapsychic conflicts (related to grief, unemployment, damage or hospitalization) or interpersonal conflicts' situations where we are confronted to stress related to socio-affective environment, lack of social support or conjugal difficulties. Medical and physiologic causes: legs impatience syndrome, recurrent limbs shakings syndrome, breathe stop during sleep, narcolepsy, excessive medicine or hypnotic drugs use, some central nervous system injuries, every nocturnal awakening (related to aches.), surgical operation. Chronobiological factors: night working or day-night shift produce insomnia by desynchronization. It is the same for time lag related to jet-lag flights. Significant gaps between the internal biological clock and environmental synchronizators, such as phase delay sleep, phase advance sleep, sleep-waking cycle longer than 24 (25) hours, or variations in sleep-awakening cycle, are of less importance. Toxic factors are numerous: amphetamines, antidepressors, medication against anorexia and tubercular disease, caffeine and alcohol excessive use, chronic alcoholism. Behavioral factors: enduring insomnias are related to poor nightroutines (to go to sleep too early, to read or to look at T.V. when going to bed). The same effect is produced by regular intellectual activities close to bedtime or by a late meal in the evening, by an noisy or unhealthy environment, by physical hyperactivity or sleeping after each lunch. Psychiatric factors: insomnia often appears with psychiatric disorders such as a major depressive episode, an anxiety disorder or schizophrenia. Insomnia also is able to open a delirious disorganization or a manic access. Psychological factors: overstimulation of waking system (related to stress overdose or intellectual hyperactivity), conditioning phenomena, fear of not falling asleep, intrapsychic and interpersonal conflicts. Third, the author put hypothesis about psychodynamic etiology of chronic insomnia. Following a first assumption, insomnia should be a result of anguish excess related to intrapsychic (and not interpersonal) conflicts which can't lead to a mental elaboration. These conflicts run over dream protective function, generating a breakdown of dream symbolization function. At a clinical level, we are in some cases in front of people enduring sleeping insomnia but more often, we are confronted with an intermittent or early waking insomnia sometimes associated with nightmares. Following a second assumption, insomnia should be a result of psychic functioning invalidation. Here, failure of dream protective and symbolization function is related to anguish excess associated with an amount of external conflicts. Overwhelmed by concretude, insomniac patients present an alexythimic intrapsychic functioning forbiding dream realization. These persons have no possibility to elaborate conflicts especially external overcharge, using dreams or imagination to escape from an intrusive reality and regress to sleeping. Here we are in front of initial sleep insomnia. Following a third hypothesis, some insomnias are related to wakings associated with repetitive nightmares. This type of insomnia should be related to a past traumatic event or activated by actual existential context and produces a too important anguish charge to follow a mental elaboration process and lead to mental symbolic representation. Following a fourth hypothesis, some insomnias are in relation with an impossibility to accept passive position. The last one will expose to a danger consisting either of castration or loneliness and death. To conclude, the author suggests some preventive perspective to face insomnia. Especially, she points out limits of pharmalogical treatments. She underlines the necessity to promote no medical methods to facilitate sleep induction and maintenance, including sleep hygiene measures, relaxation, psychotherapic approach and behavioral methods. She emphasizes the danger of a reductive approach of insomnia which would be focused on a single medical, psychological or environmental dimension. Last but not least, she makes methodological propositions to test from a clinical point of view the four psychodynamic exposed hypotheses.
 ...
PMID:[Etiology of adult insomnia]. 1250 61

Nonorganic insomnia is a frequent sleep disorder that has a high comorbidity with other psychiatric illnesses. In our sleep outpatient clinic, 41% of the patients showed neurotic, stress-related and somatoform disorders, 31% affective disorders and 1.6% schizophrenia. Sleep laboratory investigations in patients for diagnostic purposes and in normal subjects for the evaluation of drug effects suggest that changes in the sleep architecture of patients with nonorganic insomnia due to psychiatric disorders, compared with normal controls, are opposite to alterations induced by psychotropic drugs intended for their treatment, compared with placebo (key-lock principle). Evidence for this principle was found regarding nonorganic insomnia related to generalized anxiety disorder or panic disorders and benzodiazepines, depressive episodes, recurrent depression or dysthymia and sedative antidepressants and finally schizophrenia and sedative neuroleptics. Polysomnography (PSG) findings of other mental disorders are rather scarce and often depend upon the subtype and stage of the disease. In conclusion, sleep laboratory studies may be helpful for choosing the right drug for an individual insomniac patient.
 ...
PMID:The key-lock principle in the diagnosis and treatment of nonorganic insomnia related to psychiatric disorders: sleep laboratory investigations. 1257 67

A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome-X, rheumatoid arthritis and epilepsy has been described. The psychological behavioural patterns of the family were as follows--creativity and high IQ, hypersexual behaviour, reduced appetite and eating behaviour, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less of bonding and affectionate behaviour and left handedness. Digoxin, an endogenous Na(+)-K(+) ATPase inhibitor secreted by the hypothalamus, was found to be elevated and RBC membrane Na(+)-K(+) ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine resulting in increased levels of depolarising tryptophan catabolites - serotonin, quinolinic acid, strychnine and nicotine and decreased levels of hyperpolarising tyrosine catabolites dopamine, noradrenaline and morphine contributing to membrane Na(+)-K(+) ATPase inhibition in all the above disorders and the indexed family. Digoxin induced membrane Na(+)-K(+) ATPase inhibition can result in increased intracellular Ca(2+) and reduced Mg(++) levels leading to glutamate excitotoxicity, oncogene activation and immune activation. Digoxin induced altered Ca(++)/Mg(++) ratios, reduced ubiquinone and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure and mitochondrial function leading to the diverse disorders described above including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/left hemispheric dominant and left-handed/right hemispheric dominant individuals. The biochemical patterns in the indexed family and the diverse disorders studied correlated with those obtained in right hemispheric dominance. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and co-ordinate the functions of various cellular organelles.
 ...
PMID:Hypothalamic digoxin--central role in conscious perception, neuroimmunoendocrine integration and coordination of cellular function--relation to hemispheric dominance. 1260 43

The Schedule of Affective Disorders and Schizophrenia-Change Version (SADS-C; Spitzer & Endicott, 1978b) is a brief, highly reliable structured interview with clinical applications to diverse populations. This investigation involved reanalyses of data from 2 earlier studies (Rogers, Grandjean, Tillbrook, Vitacco, & Sewell, 2001; Ustad, Rogers, & Salekin, 1998). Focusing on 2 clinical samples from a metropolitan jail, we investigated its subscales via exploratory and confirmatory factor analysis. A good model fit was found (comparative fit index =.92; robust comparative fit index =.94) for 4 subscales (Dysphoria, Psychosis, Mania, and Insomnia) with good interrater reliability (M intraclass coefficient =.95) and clinical relevance. As a preliminary screen for feigned mental disorders, 2 detection scales (Symptom Combinations and Symptom Selectivity) were moderately successful. By maximizing negative predictive power, the SADS-C detection strategies proved effective at ruling out feigning for mentally disordered offenders with a high likelihood of genuine disorders.
 ...
PMID:Assessing Axis I symptomatology on the SADS-C in two correctional samples: the validation of subscales and a screen for malingered presentations. 1463 53

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of aripiprazole are discussed. Aripiprazole is a third-generation antipsychotic agent indicated for use in the treatment of schizophrenia. Unlike other antipsychotics, aripiprazole demonstrates mixed D2 and serotonin (5-HT1A) receptor agonist-antagonist activity that is hypothesized to improve schlzophrenia's positive and negative symptoms; the drug has been referred to as a dopamine-serotonin stabilizer. Aripiprazole is well absorbed, with peak plasma concentrations occurring within three to five hours after administration. The oral availability is 87%. The mean elimination half-life is about 75 hours for aripiprazole and 94 hours for its active metabolite. In controlled, randomized, multicenter trials, aripiprazole has demonstrated efficacy in the treatment of schizophrenia comparable to that of haloperidol and superior to placebo. In a single clinical trial, aripiprazole was superior to placebo in the treatment of acute mania. The most frequent adverse effects are headache, anxiety, insomnia, nausea, vomiting, and lightheadedness. Because aripiprazole is a substrate of both cytochrome P-450 isoenzymes 3A4 and 2D6, there is a potential for other drugs to affect its metabolism. The recommended starting dosage is 10 or 15 mg daily, preferably administered with meals. Aripiprazole offers an alternative to second-generation antipsychotic agents in the treatment of schizophrenia.
 ...
PMID:Aripiprazole. 1468 20

This study was undertaken to evaluate the efficacy and safety of olanzapine compared with fluphenazine in the treatment of patients who met the Diagnostic and Statistical Manual, fourth edition (DSM-IV) diagnostic criteria for schizophrenia or schizoaffective disorder. This was a long-term (22-week), randomized, double-blind, parallel clinical trial. Sixty patients (mean age, 35.4 years) were randomly assigned to either olanzapine (n=30) or fluphenazine (n=30). They received treatment at three centers in Croatia during a 22-week study period and were assessed weekly for the first 6 weeks and monthly thereafter. Efficacy was measured using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Rating Scale (PANSS) and the Clinical Global Impression (CGI) Severity and Improvement scores. The Hillside Akathisia Scale (HAS), Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), vital signs, laboratory tests, and treatment-emergent adverse events were assessed to evaluate safety. The olanzapine group showed significantly greater mean decreases from baseline to endpoint for BPRS total (-25.8 vs. -16.5, P=.035), PANSS total (-45.7 vs. -29.5, P=.037), PANSS positive (-13.0 vs. -7.9, P=.034), and CGI Severity (-2.2 vs. -1.3, P=.031) scores. The olanzapine group showed greater mean decreases on all measures of extrapyramidal symptoms, significantly so for the SAS (-2.1 vs. 1.9, P=.004) and HAS (-3.4 vs. 2.6, P=.028). Patients in the fluphenazine group experienced a higher incidence of treatment-emergent adverse events (76.7% vs. 50.0%, P=.032). Weight gain was the most frequently reported adverse event in the olanzapine group (16.7% vs. 0.0%, P=.020). Akathisia (30.0% vs. 10.0%, P=.053) and insomnia (20.0% vs. 0.0%, P=.010) appeared most frequent in the fluphenazine group. Daily use of anticholinergics and benzodiazepines were both significantly greater for the fluphenazine group (P=.003 and.04, respectively). No significant changes were observed in vital signs, ECG, or clinical chemistry. The study indicates that olanzapine has advantages in both efficacy and safety compared to fluphenazine; however, the small sample size limits our ability to draw definitive conclusions.
 ...
PMID:Double-blind, randomized comparison of olanzapine versus fluphenazine in the long-term treatment of schizophrenia. 1475 28


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>