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)

Symptoms are known to account for a small variance in some cognitive functions in schizophrenia, but the influence of self-perceived mood remains largely unknown. The authors examined the influence of subjective mood states, psychopathology, and depressive symptoms in cognitive performance in a single investigation in schizophrenia. A group of 40 stable medicated patients with schizophrenia (20 men, 20 women) and 30 healthy comparison subjects (15 men, 15 women) were assessed on neurocognitive measures of verbal abilities, attention, executive functioning, language, memory, motor functioning, and information processing. All subjects provided self-ratings of mood prior to cognitive testing. Patients were also rated on psychopathology and depressive symptoms. Patients performed worse than comparison subjects on most cognitive domains. Within the patient group, subjective feelings of depression-dejection, fatigue-inertia, confusion, and tension-anxiety predicted (controlling for symptoms) poor performance on measures of attention, executive function, and verbal memory. In the same group of patients, clinician-rated symptoms of psychopathology and depression predicted significantly poor performance only on tests of motor function. In comparison subjects, vigor related to better, and fatigue and inertia to worse, spatial motor performance. Self-perceived negative mood state may be a better predictor of cognitive deficits than clinician-rated symptoms in chronic schizophrenia patients.
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PMID:Does self-perceived mood predict more variance in cognitive performance than clinician-rated symptoms in schizophrenia? 1676 Apr 21

Perospirone is a recently developed atypical antipsychotic with potent serotonin 5-HT2 and dopamine D2 antagonist activity. Other atypical antipsychotics including risperidone, quetiapine and olanzapine have been widely used for treatment, not only for schizophrenia symptoms but also for delirium, because of their low potential to induce extrapyramidal disturbances. In the present study the effectiveness and safety of perospirone in patients with delirium are described. Thirty-eight patients with DSM-IV delirium were given open-label perospirone. To evaluate the usefulness of perospirone, scores from 13 severity items of the Delirium Rating Scale-Revised-98 were assessed. Data were gathered from October 2003 to September 2004. Perospirone was effective in 86.8% (33/38) of patients, and the effect appeared within several days (5.1 +/- 4.9 days). The initial dose was 6.5 +/- 3.7 mg/day and maximum dose of perospirone was 10.0 +/- 5.3 mg/day. There were no serious adverse effects. However, increased fatigue (15.2%), sleepiness (6.1%), akathisia (3.0%) and a decline in blood pressure (3.0%) were observed. It is proposed that perospirone may be another safe and effective atypical antipsychotic drug for the treatment of delirium symptoms in hospitalized patients. This is a preliminary open trial, and further randomized double-blind placebo-controlled tests are needed.
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PMID:Perospirone in the treatment of patients with delirium. 1723 41

AMPA-receptor-positive modulators (Ampakines) facilitate learning and memory in animal models and in preliminary trials in human subjects. CX516 is the first Ampakine to be studied for cognitive enhancement in schizophrenia. Stable schizophrenia patients treated with clozapine (n=52), olanzapine (n=40), or risperidone (n=13) were randomly assigned to add-on treatment with CX516 900 mg three times daily or placebo for 4 weeks. Subjects were assessed with a cognitive battery at baseline, week 4, and at 4-week follow-up. Clinical scales and safety monitoring were also performed. The primary endpoint was the change from baseline in a composite cognitive score at week 4 for the intent-to-treat sample. Additional analyses examined change in symptom rating scores and examined drug effects on patients treated with clozapine separately from patients treated with either olanzapine or risperidone. A total of 105 patients were randomized and 95 (90%) completed the 4-week trial. Patients treated with CX516 did not differ from placebo in change from baseline on the composite cognitive score, or on any cognitive test at weeks 4 or 8. The between groups effect size at week 4 for the cognitive composite score was -0.19 for clozapine-treated patients and 0.24 for patients treated with olanzapine or risperidone. The placebo group improved more on the PANSS total score than the CX516 group; no other clinical rating differed between treatment groups. CX516 was associated with fatigue, insomnia and epigastric discomfort compared to placebo, but was generally well tolerated. CX516 was not effective for cognition or for symptoms of schizophrenia when added to clozapine, olanzapine, or risperidone.
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PMID:A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia. 1748 27

Psychotic symptoms such as delusions and hallucinations can have a devastating effect on a patient's social functioning. Since psychosis is rarely congenital, it is possible that lifestyle factors play a role in its etiology. This paper offers a hypothesis that some of these factors could be: (a) A lifestyle lacking evolutionarily conserved stressors such as frequent exposure to heat and/or cold, resulting in a lack of "thermal exercise" which could lead to malfunctioning of the brain. (b) Partial retention and absorption of toxic waste in the colon, as described in more detail below. (c) Genetic makeup that makes a person vulnerable to the above conditions. To test the hypothesis, three types of hydrotherapy are proposed (to be tested separately) as a putative neuroleptic treatment: head-out hot showers, adapted cold showers (twice daily each), and colon hydrotherapy (every 3-12 weeks, which also includes a dietary change according to Harvard's Healthy Eating Pyramid). The following is supporting evidence: Dopaminergic transmission in the mesolimbic pathway is involved in central processing of pain and negative stimuli (e.g. stress-induced analgesia) in addition to its role in the pathophysiology of psychosis. It is also known that if a neural pathway can perform two different functions, then the execution of one function will often suppress the other (e.g. gate control theory of pain). Thus, a pain-based therapy, such as a moderately hot shower, could have a "crowding out" effect on pathological processes within the mesolimbic system. In addition, hyperthermia is known to induce fatigue and depress activity of the frontal cortex (the sedative effect). As described previously, an adapted cold shower could work as a mild electroshock applied to the sensory cortex and, therefore, it might have an antipsychotic effect similar to that of electroconvulsive therapy. Additionally, a cold shower is a vivid example of stress-induced analgesia and would also be expected to "crowd out" or suppress psychosis-related neurotransmission within the mesolimbic system. Human and bacterial toxic waste can sometimes be partially retained in the colon and it is known that many high-molecular-weight compounds can be absorbed there. Most narcotics can cause intoxication if administered rectally and there is also significant comorbidity of schizophrenia with intestinal illnesses. Additionally, there is indirect evidence that colon cleansing can significantly improve mental state. Therefore, it is possible that chronic intoxication with yet unknown components of partially retained waste could be one of the unrecognized organic causes of psychosis.
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PMID:Hydrotherapy as a possible neuroleptic and sedative treatment. 1764 Aug 27

Most previous studies of attention deficit in ADHD and schizophrenia have used overall measures of inattention that may disguise differences in underlying mechanisms. The present study investigated types of inattentive errors and applied a process view of attention in analyses of Conners' Continuous Performance Test protocols from subjects with ADHD-combined (51), inattentive type (19) and schizophrenia (26). Subjects with ADHD-I had more omission errors and became more inattentive as a function of time on task. Subjects with ADHD-C made more errors of commissions as time passed. In contrast, the performance of the subjects with schizophrenia improved, indicating a training effect. There were no differences in overall attentiveness between the groups. Although all groups were impaired on an overall level, they displayed three distinct patterns of inattention. The ADHD-I group displayed a lethargic inattention characterized by high fatigue. The ADHD-C group showed a hyperactive-impulsive pattern, while the schizophrenia group showed an inability to initially focus attention.
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PMID:Differentiating attention deficit in adult ADHD and schizophrenia. 1764 Aug 49

Modafinil is a wake-promoting agent that is pharmacologically different from other stimulants. It has been investigated in healthy volunteers, and in individuals with clinical disorders associated with excessive sleepiness, fatigue, impaired cognition and other symptoms. This review examines the use of modafinil in clinical practice based on the results of randomized, double-blind, placebo-controlled clinical trials available in the English language in the MEDLINE database. In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action. Evidence for improved cognition in non-sleep-deprived healthy volunteers is controversial.Modafinil improves excessive sleepiness and illness severity in all three disorders for which it has been approved by the US FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure (CPAP). However, its effects on safety on the job and on morbidities associated with these disorders have not been ascertained. Continued use of CPAP in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In very small, short-term trials, modafinil improved excessive sleepiness in patients with myotonic dystrophy. It was efficacious in fairly large studies of attention deficit hyperactivity disorder (ADHD) in children and adolescents, and was as efficacious as methylphenidate in a small trial, but has not been approved by the FDA, in part because of its serious dermatological toxicity. In a trial of 21 non-concurrent subjects, with 2-week treatment periods, modafinil was as effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive symptoms in bipolar disorder in a trial that excluded patients with stimulant-induced mania. A single dose of modafinil may hasten recovery from general anaesthesia after day surgery. A single dose of modafinil improved the ability of emergency room physicians to attend didactic lectures after a night shift, but did not improve their ability to drive home and caused sleep disturbances subsequently.Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo.Trials of modafinil for excessive sleepiness in Parkinson's disease, cocaine addiction and cognition in chronic fatigue syndrome provided inconsistent results; all studies had extremely small sample sizes. Modafinil cannot be recommended for these conditions until definitive data become available.Modafinil induces and inhibits several cytochrome P450 isoenzymes and has the potential for interacting with drugs from all classes. The modafinil dose should be reduced in the elderly and in patients with hepatic disease. Caution is needed in patients with severe renal insufficiency because of substantial increases in levels of modafinil acid. Common adverse events with modafinil include insomnia, headache, nausea, nervousness and hypertension. Decreased appetite, weight loss and serious dermatological have been reported with greater frequency in children and adolescents, probably due to the higher doses (based on bodyweight) used. Modafinil may have some abuse/addictive potential although no cases have been reported to date.
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PMID:Approved and investigational uses of modafinil : an evidence-based review. 1872 34

Selected biochemical evidence suggests a potential role for n-3 long-chain PUFA (n-3PUFA) in the regulation of mood and behaviour. The present paper reviews the relevant evidence, to date, from epidemiological studies, clinical studies and intervention trials. Most evidence is available investigating a role for n-3PUFA in depression, depressive illness and suicidal behaviour, but work is also available on anxiety and anxiety-related disorders, fatigue and fatigue-related disorders, aggression, hostility and anti-social behaviour, inattention, impulsivity and attention deficit hyperactivity disorder and schizophrenic disorders. For all these aspects of mood and behaviour, the evidence available is currently limited and highly inconsistent, both in terms of study methodology and study findings. There is a clear need for further work in this area.
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PMID:Is there a role for n-3 long-chain polyunsaturated fatty acids in the regulation of mood and behaviour? A review of the evidence to date from epidemiological studies, clinical studies and intervention trials. 1907 52

Computerized ambulatory monitoring overcomes a number of methodological and conceptual challenges to studying mental disorders, however concerns persist regarding the feasibility of this approach with severe psychiatric samples and the potential of intensive monitoring to influence data quality. This multi-site investigation evaluates these issues in four independent samples. Patients with schizophrenia (n = 56), substance dependence (n = 85), anxiety disorders (n = 45), and a non-clinical sample (n = 280) were contacted to participate in investigations using computerized ambulatory monitoring. Micro-computers were used to administer electronic interviews several times per day for a one-week period. Ninety-five percent of contacted individuals agreed to participate in the study, and minimum compliance was achieved by 96% of these participants. Seventy-eight percent of all programmed assessments were completed overall, and only 1% of micro-computers were not returned to investigators. There was no evidence that missing data or response time increased over the duration of the study, suggesting that fatigue effects were negligible. The majority of variables investigated did not change in frequency as a function of study duration, however some evidence was found that socially sensitive behaviors changed in a manner consistent with reactivity.
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PMID:Computerized ambulatory monitoring in psychiatry: a multi-site collaborative study of acceptability, compliance, and reactivity. 1919 50

Close similarities in the courses of multiple sclerosis and schizophrenia laid the theoretical ground for attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae, which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is postulated that since rickettsial microorganisms are ubiquitous in human populations they and the human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of them may become aggressive and pathogenic. The kynurenic acid hypothesis of schizophrenia has attracted much attention. It also seems to have initiated a paradigmatic shift from the hitherto prevailing serological research approach to one which focuses on immunological factors. An open clinical pilot study in which, during 2006, eight female and five male patients with psychotic symptoms were treated with a combination of antibiotics is presented, to which, in the beginning of 2007 two female patients suffering from severe and long standing chronic fatigue syndrome were added. On one year follow-up, six out of the eight female patients showed stable excellent treatment results, whereas two were rated as showing significant treatment results. Four of the five men who entered the study were suffering from chronic schizophrenia, whereas the fifth, was a case of severe acute catatonic schizophrenia. Two of the male patients showed significant treatment results, whereas three of them were rated as having had a slight to moderate improvement. No less than three of the women had suffered their first episode of psychosis after giving birth to their first (and only) child. This finding, as these women all responded excellently to treatment with antibiotics, indicates that post partum psychosis could be regarded as an infectious complication of childbirth of, as to the causative agent, unknown aetiology. High priority ought therefore be given to initiate controlled clinical trials with antibiotic treatment of this serious condition. The otherwise promising results of the pilot study seem to warrant further and controlled clinical trials with treatment with antibiotics of patients with psychotic symptoms. As the second patient with psychotic symptoms to enter the study, had a long standing history of chronic fatigue, where an initial treatment with the antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided, when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic in February and March 2007, to include them in the study. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement.
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PMID:On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics. 2003 36

Atypical antipsychotic medications like olanzapine (OLZ) induce weight gain and increase the risk of diabetes in patients with schizophrenia. The goal of this study was to assess potential mechanisms of OLZ-induced weight gain and accompanying metabolic effects. Healthy, lean, male volunteers received OLZ and placebo (PBO) in a randomized, double-blind, crossover study. In periods 1 and 2, subjects received OLZ (5 mg for 3 days then OLZ 10 mg for 12 days) or matching PBO separated by a minimum 12-day washout. Twenty-four hour food intake (FI), resting energy expenditure (REE), activity level, metabolic markers, and insulin sensitivity (IS) were assessed. In total, 30 subjects were enrolled and 21 completed both periods. Mean age and BMI were 27 years (range: 18-49 years) and 22.6 +/- 2.2 kg/m(2), respectively. Relative to PBO, OLZ resulted in a 2.62 vs. 0.08 kg increase in body weight (P < 0.001) and 18% (P = 0.052 or 345 kcal) increase in FI. Excluding one subject with nausea and dizziness on the day of OLZ FI measurement, the increase in FI was 547 kcal, (P < 0.05). OLZ increased REE relative to PBO (113 kcal/day, P = 0.003). Significant increases in triglycerides, plasminogen activator inhibitor-I (PAI-I), leptin, and tumor necrosis factor-alpha (TNF-alpha) were observed. No significant differences in activity level or IS were observed. This study provides evidence that OLZ pharmacology drives the early increase in weight through increased FI, without evidence of decreased energy expenditure (EE), activity level, or short-term perturbations in IS.
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PMID:Increased food intake and energy expenditure following administration of olanzapine to healthy men. 2013 8


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