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)

Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.
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PMID:Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. 1085 51

Several case studies indicate that clozapine use is associated with reductions in the use of nicotine, alcohol, or illicit drugs. Although not designed to assess clozapine, this study explored a posteriori the effects of clozapine on alcohol and drug use disorders among schizophrenia patients. Among 151 patients with schizophrenia or schizoaffective disorder and co-occurring substance use disorder who were studied in a dual-disorder treatment program, 36 received clozapine during the study for standard clinical indications. All participants were assessed prospectively at baseline and every 6 months over 3 years for psychiatric symptoms and substance use. Alcohol-abusing patients taking clozapine experienced significant reductions in severity of alcohol abuse and days of alcohol use while on clozapine. For example, they averaged 54.1 drinking days during 6-month intervals while off clozapine and 12.5 drinking days while on clozapine. They also improved more than patients who did not receive clozapine. At the end of the study, 79.0 percent of the patients on clozapine were in remission from alcohol use disorder for 6 months or longer, while only 33.7 percent of those not taking clozapine were remitted. Findings related to other drugs in relation to clozapine were also positive but less clear because of the small number of patients with drug use disorders. This study was limited by the naturalistic design and the lack of prospective, standardized measures of clozapine use. The use of clozapine by patients with co-occurring substance disorders deserves further study in randomized clinical trials.
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PMID:The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. 1088 42

Because clozapine may be prescribed to cocaine abusing patients with schizophrenia, we studied cocaine-clozapine interactions in a controlled setting. Eight male cocaine addicts underwent four oral challenges with ascending doses of clozapine (12.5, 25 and 50 mg) and placebo followed 2 h later by a 2-mg/kg dose of intranasal cocaine. Subjective and physiological responses, and serum cocaine levels were measured over a total 4-h period. Clozapine pretreatment increased cocaine levels during the study and significantly increased the peak serum cocaine levels in a dose dependent manner. In spite of this elevation in blood levels, clozapine pretreatment had a significant diminishing effect upon subjective responses to cocaine, including 'expected high', 'high' and 'rush', notably at the 50 mg dose. There was also a significant effect upon 'sleepiness', 'paranoia' and 'nervous'. Clozapine caused a significant near-syncopal episode in one subject in the study, requiring his removal from the study. Clozapine had no significant effect on baseline pulse rate and systolic blood pressure, but it attenuated the significant pressor effects of the single dose of intranasal cocaine. These data suggested a possible therapeutic role for clozapine in the treatment of cocaine addiction in humans, but also suggests caution due to the near-syncopal event and the increase in serum cocaine levels.
Drug Alcohol Depend 2000 May 01
PMID:Significant interaction between clozapine and cocaine in cocaine addicts. 1089 28

Glutamatergic NMDA receptors are believed to play a major role in the pathophysiology of numerous neuropsychiatric disorders including substance use and schizophrenia. Neuropharmacological studies measuring subjective response, psychopathology and biological parameters are helpful in studying pathophysiology of these disorders. We report preliminary data of a placebo-controlled double-blind challenge study in recently detoxified alcoholics (n = 20) and healthy controls (n = 10) using the non-competitive NMDA antagonist dextromethorphan. Findings suggest that dextrometorphan can produce ethanol-like subjective effects in both alcoholics and controls and induce a mild form of craving in alcoholics only. The results of this study give further support to the hypothesis of glutamatergic NMDA receptors mediating much of ethanol's psychotropic effects. Possible clinical implications of these findings are discussed.
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PMID:NMDA receptor challenge with dextromethorphan - subjective response, neuroendocrinological findings and possible clinical implications. 1094 10

The appearance of cavum septi pellucidi (CSP) has been already connected with developmental disorders or with serious psychiatric diseases (schizophrenia, maniac-depressive disorder, aggressiveness or similar). During our investigation of CSP, group of alcoholics seemed to be interesting for investigation and comparison with the groups of schizophrenics and people with violent behavior. We obtained CSP in 205 out of 670 fixed brains (429 male and 241 female) of persons aged from 14 to 89 (mean +/- SD: 53.28 +/- 16.57), 85 cava belonged to our group of interest. Prevalence of CSP in aforementioned groups was significantly higher than in the rest of examined population. Only in the group of 20 to 39 years of age all kinds of obtained pathologies were present. Alcoholics with CSP suffered from cardiovascular diseases and died accidentally and aggressive persons were the only drug addicts in our examined group and they had the shortest life span. 34 out of 41 schizophrenics had no data about prior diseases and disorders and they were the ones who committed suicide frequently. Intensive demyelinization of corpus callosum and transformation of potential space between laminae of septum pellucidum to the actual one could explain the CSP appearance among alcoholics. To our opinion, cavum septi pellucidi might be used as an additional marker of organic brain changes in long term alcohol abuse, as a consequence of demyelinization due to lipolytic effect of ethanol, and lower cerebral blood flow.
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PMID:Comparative post-mortem study of cavum septi pellucidi in alcoholics, schizophrenics and aggressive persons. 1100 Aug 86

Animal models are important tools in the study of psychiatric disorders, including alcoholism, because they allow the use of research methods that cannot be used for ethical reasons in humans. Consequently, scientists have developed numerous approaches to evaluate the validity and reliability of animal models for studying human behavior and human disorders. Researchers have developed animal models of schizophrenia, fear and anxiety, depression, and alcoholism, all of which are being used to study the relationship between alcoholism and co-occurring psychiatric disorders. These models may help researchers and clinicians determine how best to treat patients with alcoholism and co-occurring psychiatric disorders.
Alcohol Res Health 2000
PMID:Animal models of psychiatric disorders and their relevance to alcoholism. 1119 84

Zinc has several crucial functions in brain development and maintenance: it binds to p53, preventing it from binding to supercoiled DNA and ensuring that p53 cause the expression of several paramount genes, such as the one that encodes for the type I receptors to pituitary adenine cylase-activator peptide (PACAP), which directs embryonic development of the brain cortex, adrenal glands, etc.; it is required for the production of CuZnSOD and Zn-thionein, which are essential to prevent oxidative damage; it is required for many proteins, some of them with Zn fingers, many of them essential enzymes for growth and homeostasis. For example, the synthesis of serotonin involves Zn enzymes and since serotonin is necessary for melatonin synthesis, a Zn deficiency may result in low levels of both hormones. Unfortunately, Zn levels tend to be low when there is excess Cu and Cd. Moreover, high estrogen levels tend to cause increased absorption of Cu and Cd, and smoking and eating food contaminated with Cd result in high levels of the latter. Furthermore, ethanol ingestion increases the elimination of Zn and Mg (which acts as a cofactor for CuZnSOD). Increased Cu levels may also be found in people with Wilson's disease, which is a rather rare disease. However, the heterozygote form (only one faulty copy of the chromosome) is not so rare. Therefore, the developing fetus of a pregnant women who is low in Zn and high in Cu may experience major difficulties in the early development of the brain, which may later manifest themselves as schizophrenia, autism or epilepsy. Similarly, a person who gradually accumulates Cu, will tend to experience a gradual depletion of Zn, with a corresponding increase in oxidative damage, eventually leading to Parkinson's disease. Also discussed are the crucial roles of histidine, histamine, vitamin D, essential fatty acids, vitamin E, peroxynitrate, etc. in the possible oxidative damage involved in these mental diseases.
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PMID:Micronutrient accumulation and depletion in schizophrenia, epilepsy, autism and Parkinson's disease? 1138 83

Ketamine blocks the calcium channel associated with N-methyl-D-aspartate (NMDA) glutamate receptors. It has transient behavioral effects in healthy humans that resemble aspects of schizophrenia, dissociative disorders, and ethanol intoxication. Ethanol is an antagonist of both NMDA receptors and L-type voltage-sensitive calcium channels (VSCC) and it has minimal psychotogenic activity in humans. A double-blind placebo-controlled study was conducted that evaluated whether pretreatment with the L-type VSCC antagonist, nimodipine, 90 mg D, modulated ketamine response (bolus 0.26 mg/kg, infusion of 0.65 mg/kg/hr) in 26 ethanol-dependent inpatients who were sober for at least one month prior to testing. This study found that nimodipine reduced the capacity of ketamine to induce psychosis, negative symptoms, altered perception, dysphoria, verbal fluency impairment, and learning deficits. Nimodipine improved memory function, but had no other intrinsic behavioral activity in this patient group. Nimodipine pretreatment attenuated the perceived similarity of ketamine effects to ethanol as well as ketamine-induced euphoria and sedation. However, nimodipine did not reduce the stimulant effects of ketamine. These data suggest that antagonism of L-type VSCCs attenuates the behavioral effects of NMDA antagonists in humans. They support the continued evaluation of nimodipine in the treatment of neuropsychiatric disorders. They also suggest that drugs, such as ethanol, that combine NMDA and L-type VSCC antagonism may have enhanced tolerability without attenuation of their stimulant effects.
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PMID:Attenuation of ketamine effects by nimodipine pretreatment in recovering ethanol dependent men: psychopharmacologic implications of the interaction of NMDA and L-type calcium channel antagonists. 1175 Jan 86

Anticonvulsant agents show promise in the treatment of the acute symptoms of alcohol withdrawal and may also treat some symptoms associated with the protracted abstinence syndrome. Impulsivity, hostility and irritability are common characteristics of alcohol-dependent individuals, and there is some evidence that anticonvulsant agents decrease these traits in individuals with a number of different psychiatric disorders. This pilot study is a 12-week, double-blind, placebo-controlled trial of an anticonvulsant agent, divalproex (DVPX), in alcohol-dependent individuals. Alcohol use (Timeline Follow Back), impulsivity (Barratt Impulsivity Scale), irritability and aggression (Buss-Durkee Hostility Index; and Anger, Irritability, Aggression Scale) were measured at baseline and throughout the 12-week treatment period. Drinking decreased significantly in both the placebo and the DVPX-treated groups. In the DVPX group, a significantly smaller percentage of individuals relapsed to heavy drinking, but there were no significant differences in other alcohol-related outcomes. There were significantly greater decreases in irritability in the DVPX-treated group and a trend towards greater decreases on measures of lability and verbal assault. There were no significant between-group differences on measures of impulsivity. While DVPX did not have a robust effect on alcohol-related outcomes, it did have modest impact on a measure of irritability. This is consistent with the findings of other investigators exploring the use of DVPX in schizophrenia, personality disorder and a number of other psychiatric disorders.
Drug Alcohol Depend 2002 Aug 01
PMID:The use of divalproex in alcohol relapse prevention: a pilot study. 1212 3

Abnormalities in monoamine neurotransmission have been implicated in the pathogenesis of alcoholism, mood disorders and schizophrenia. Murine norepinephrine transporter gene (NET) has been mapped to a region on chromosome 8 where a quantitative trait locus for ethanol sensitivity. Therefore we tested whether norepinephrine transporter (NET) gene variants confer susceptibility to either alcohol dependence or severe alcohol withdrawal symptoms. There is a highly polymorphic silent G1287A mutation in the NET gene. In our study 157 alcoholics and 185 healthy unrelated matched control subjects were analyzed for a silent G1287A mutation. No significant differences in allele and genotype distribution between control subjects f(A)=0.33 and alcoholics f(A)=0.29 were found. No significant results were found in more homogenous subgroups, i.e. alcoholics with severe alcohol withdrawal (seizures, delirium), early onset age<26 nor dependent patients with positive familial history of alcoholism. These results suggest that the NET gene polymorphism in exon 9 accession number: mRNA: NM_001043, genomic contig.: NT_019610, is unlikely to be involved in the susceptibility to alcoholism and severe alcohol withdrawal.
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PMID:Norepinephrine transporter gene polymorphism is not associated with susceptibility to alcohol dependence. 1237 39


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