Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fetal alcohol syndrome (FAS) stems from maternal alcohol abuse during pregnancy and is an important cause of mental retardation and hyperactivity in children. In the developing brain, alcohol can kill neurons, leading to microencephaly. However, due to their genetic makeup, some individuals are less vulnerable than others to alcohol's neurotoxic effects. Animal studies have demonstrated that one particular gene, neuronal nitric oxide synthase (nNOS), protects developing neurons in vivo against alcohol-induced death. We utilized pharmacologic techniques to demonstrate that nNOS protects neurons against alcohol toxicity by activating the NO-cGMP-PKG signaling pathway. Cerebellar granule cell cultures derived from mice carrying a null mutation for nNOS (nNOS-/- mice) were substantially more vulnerable than cultures from wild-type mice to alcohol-induced cell death. However, activation of the pathway at sites downstream of nNOS protected the cultures against alcohol toxicity. Conversely, blockade of the pathway rendered wild-type cultures vulnerable to alcohol-induced death. We further identified NF-kappaB as the downstream effector through which nNOS and the NO-cGMP-PKG pathway signal their neuroprotective effects. Tumor necrosis factor-alpha (TNF-alpha), which activates NF-kappaB, ameliorated alcohol-induced cell death in nNOS-/- and wild-type cultures, while an NF-kappaB inhibitor (NFi) blocked the protective effects of TNF-alpha and worsened alcohol-induced cell death. Furthermore, NFi blocked the protective effects of NO-cGMP-PKG pathway activators, demonstrating that NF-kappaB is downstream of the NO-cGMP-PKG pathway. As wild-type neurons matured in culture, they became resistant to alcohol toxicity. However, this maturation-dependent alcohol resistance did not occur in nNOS-/- mice and could be reversed in wild-type mice with NFi, demonstrating that nitric oxide and NF-kappaB are crucial for the development of alcohol resistance with age. Thus, nNOS protects developing neurons against alcohol toxicity by activating the NO-cGMP-PKG-NF-kappaB pathway and is crucial for the acquisition of maturation-dependent alcohol resistance.
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PMID:The protective effect of neuronal nitric oxide synthase (nNOS) against alcohol toxicity depends upon the NO-cGMP-PKG pathway and NF-kappaB. 1882 32

Fetal Alcohol Syndrome (FAS) occurs in approximately 3 of 1,000 live births in the general population of the U.S. and is the leading known cause of mental retardation. The Midwest Regional Fetal Alcohol Syndrome Training Center (MRFASTC) surveyed 1,000 licensed occupational therapists (OT) of the American Occupational Therapists Association in a six-state Midwest region, including Missouri, Iowa, Nebraska, Kansas, Oklahoma, and Arkansas to assess knowledge and attitudes regarding FAS. Nearly 20% of the OTs responded. Of the respondents, nearly 94% regarded at least 1 drink per day as being 'heavy' in a pregnant woman. There was an increase in the number of respondents who thought it was acceptable to consume 1 drink or more with each advancing trimester of pregnancy. 92% of the OTs indicated a willingness to counsel a mother of a child having FAS, but 96% indicated a poor to fair ability to select valid and reliable assessment instruments for screening a child for FAS. Only 6% of the OT respondents indicated a good-excellent ability to conduct brief interventions on alcohol cessation for women. The data collectively indicate OTs possess similarities to other health care providers, including physicians and psychologists, in the misunderstanding or deficits of knowledge and skills associated with FAS and that they are largely unprepared to provide intervention for women 'at risk' for FAS, or to recognize correctly FAS in children. There is a demonstrated need, and desire, by the practicing OTs for continued education related to alcohol abuse associated with FAS.
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PMID:Knowledge and attitudes about fetal alcohol syndrome, fetal alcohol spectrum disorders, and alcohol use during pregnancy by occupational therapists in the Midwest. 1975 93

Violence committed by acute psychiatric inpatients represents an important and challenging problem in clinical practice. Sociodemographic, clinical, and treatment information were collected for 1324 patients (677 men and 647 women) admitted to Italian public and private acute psychiatric inpatient facilities during an index period in 2004, and the sample divided into 3 groups: nonhostile patients (no episodes of violent behavior during hospitalization), hostile patients (verbal aggression or violent acts against objects), and violent patients (authors of physical assault). Ten percent (N = 129) of patients showed hostile behavior during hospitalization and 3% (N = 37) physically assaulted other patients or staff members. Variables associated with violent behavior were: male gender, <24 years of age, unmarried status, receiving a disability pension, having a secondary school degree, compulsory admission, hostile attitude at admission, and a diagnosis of schizophrenia, bipolar disorder, personality disorder, mental retardation, organic brain disorder or substance/alcohol abuse. Violent behavior during hospitalization was a predictive factor for higher Brief Psychiatric Rating Scale scores and for lower Personal and Social Performance scale scores at discharge. Despite the low percentage of violent and hostile behavior observed in Italian acute inpatient units, this study shed light on a need for the careful assessment of clinical and treatment variables, and greater effort aimed at improving specific prevention and treatment programs of violent behavior.
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PMID:Violent behavior in acute psychiatric inpatient facilities: a national survey in Italy. 1982 7

The Fragile X syndrome is caused by a CGG repeat expansion >200 in the promoter of the Fragile X mental retardation 1 (FMR1) gene termed full mutation (FM). These alleles are silenced through methylation of the FMR1 promoter, leading to deficit of the FMR1 protein (FMRP), and neurodevelopmental changes. However, occasional FM individuals have a complete lack of methylation, and those typically have only minor deficit of FMRP levels compared with normal controls and their intelligence may be in the normal range. FM alleles are generated through expansion of the CGG repeat from the premutation (PM) range of 55-200 repeats, linked to the late onset Fragile X-associated tremor/ataxia syndrome (FXTAS). This disorder has been attributed to a 'toxicity' of the FMR1 mRNA, which is significantly elevated in male carriers of PM alleles and of unmethylated FM alleles. This is the first report of a 65-year-old male with an unmethylated FM allele and history of alcohol abuse, who developed symptoms of FXTAS. We postulate that, although the elevation of FMR1 transcripts associated with unmethylated FM alleles have a potential to cause FXTAS, in some cases this disorder may occur through an additional effect of exposure to neurotoxicants including alcohol.
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PMID:Fragile X-associated tremor/ataxia phenotype in a male carrier of unmethylated full mutation in the FMR1 gene. 2147 92

Fetal alcohol spectrum disorders, the most common preventable cause for mental retardation, is the result of prenatal alcohol exposure. There is no safe amount of alcohol during pregnancy. Native Americans have a higher risk of alcohol abuse than the general U.S. population. The fetal alcohol spectrum disorders prevalence rates for Native Americans range from 1.0 to 8.97 per 1000 births. Nurses and health care providers working in collaboration with tribal fetal alcohol spectrum disorders prevention specialists can greatly, and positively, impact the physical and mental health and well-being of children in Native American communities.
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PMID:Fetal alcohol spectrum disorders: a Native American journey to prevention. 2163 17

When a mother abuses alcohol during pregnancy, the offspring can suffer a myriad of abnormalities, collectively known as fetal alcohol spectrum disorder (FASD). Foremost among these abnormalities is central nervous system dysfunction, which commonly manifests itself as mental retardation, clumsiness, hyperactivity, and poor attention span. These behavior problems are due, in large part, to alcohol-induced neuronal losses in the developing fetal brain. However, not all fetuses are equally affected by maternal alcohol consumption during pregnancy. While some fetuses are severely affected and develop hallmarks of FASD later in life, others exhibit no evident neuropathology or behavioral abnormalities. This variation is likely due, at least in part, to differences in fetal genetics. This review focuses on one particular gene, neuronal nitric oxide synthase, whose mutation worsens alcohol-induced neuronal death, both in vitro and in vivo. In addition, ectopic expression of the neuronal nitric oxide synthase gene protects neurons against alcohol toxicity. The gene encodes an enzyme that produces nitric oxide (NO), which facilitates the protective effects of neuronal growth factors and which underlies the ability of neurons to resist alcohol toxicity as they mature. Nitric oxide exerts its protective effects against alcohol via a specific signaling pathway, the NO-cGMP-PKG pathway. Pharmacologic manipulation of this pathway could be of therapeutic use in preventing or ameliorating FASD.
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PMID:The neuronal nitric oxide synthase (nNOS) gene and neuroprotection against alcohol toxicity. 2567 65

Ethanol abuse affects virtually all organ systems and the central nervous system (CNS) is particularly vulnerable to excessive ethanol exposure. Ethanol exposure causes profound damages to both the adult and developing brain. Prenatal ethanol exposure induces fetal alcohol spectrum disorders (FASD) which is associated with mental retardation and other behavioral deficits. A number of potential mechanisms have been proposed for ethanol-induced brain damage; these include the promotion of neuroinflammation, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, and thiamine deficiency. The endoplasmic reticulum (ER) regulates posttranslational protein processing and transport. The accumulation of unfolded or misfolded proteins in the ER lumen triggers ER stress and induces unfolded protein response (UPR) which are mediated by three transmembrane ER signaling proteins: pancreatic endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). UPR is initiated to protect cells from overwhelming ER protein loading. However, sustained ER stress may result in cell death. ER stress has been implied in various CNS injuries, including brain ischemia, traumatic brain injury, and aging-associated neurodegeneration, such as Alzheimer's disease (AD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). However, effects of ethanol on ER stress in the CNS receive less attention. In this review, we discuss recent progress in the study of ER stress in ethanol-induced neurotoxicity. We also examine the potential mechanisms underlying ethanol-mediated ER stress and the interaction among ER stress, oxidative stress and autophagy in the context of ethanol neurotoxicity.
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PMID:Endoplasmic Reticulum Stress and Ethanol Neurotoxicity. 2647 40

Over the last two decades, drug and alcohol abuse by pregnant women has spread to epidemic proportions. Maternal drug abuse has neurobehavioral and somatic effects which may be long-lasting and devastating to the offspring. Opiates, such as heroin and pain killers that contain a narcotic component, are widely abused today. A prominent manifestation of fetal exposure to these drugs is the neonatal withdrawal syndrome, which typically includes wakefulness, jitteriness and other symptoms of cerebral irritability. These, in turn, may interrupt early mother-infant interaction, affecting the infant's long-term emotional and cognitive development. Fetal cocaine exposure may cause neonatal cerebral irritability, changes in habituation responses, reduced head circumference, poor mental development and long-lasting impairment of the brain. Benzodiazepines can cause fetal dysmorphism (including microcephaly), neurological and behavioral impairments and neonatal withdrawal symptoms. Maternal use of amphetamines may cause neonatal dysphoria and agitation, as well as long-term lassitude and drowsiness that may result in poor feeding. Fetal exposure to alcohol may cause neonatal withdrawal symptoms, maladaptive behavior in childhood and the fetal alcohol syndrome (including microcephaly). Maternal alcohol consumption is also a common cause of mental retardation. Fetal exposure to marijuana may delay maturation of the visual system and impair memory and verbal performance at 2 years of age. The inevitable conclusion is that society must seek ways not only to treat, but also to prevent this epidemic. To this end, a key factor would be to identify potential drug abusing mothers before they reach the stage of prenatal care and educate them regarding the fatal consequences of drug abuse.
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PMID:Neonatal withdrawal syndrome and behavioral effects produced by maternal drug use. 2673 21

A 68-year-old woman, presented with a squamous cell carcinoma of the malar region, and underwent wide local excision. During her clinical examination, repetitive protrusion and intrusion of the tongue as well as stereotypic, abnormal movements of the mouth and lips were observed, in a pattern that resembled chewing, sucking or lip pursing; dyskinesias ceased when she was speaking or bringing food to the mouth. She was unaware of the movements and the tongue was observed to move similar to choreiform movements, while revealing a giant "snake-like" macroglossia. She had history of mental retardation and alcohol abuse, and was under classic antipsychotic medications for several years. During a previous neurological investigation, type I Chiari malformation was diagnosed. In this case, concomitant Chiari malformation and neuroleptic-induced tardive dyskinesia, may together have been responsible for giant macroglossia, and to our best knowledege no similar observation has been reported in the literature.
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PMID:Giant Tongue in a Patient With Chiari Malformation and Neuroleptic-Induced Tardive Dyskinesia. 3061 96

Objective: Body mass index undergoes a substantial change in some psychiatric disorders. This study aimed to explore the status of body mass index (BMI) in different psychiatric disorders in a national survey among children and adolescents and to identify the role of gender in this regard. Method : A total of 30 532 children and adolescents were randomly selected using cluster sampling method with equal blocks of three age groups and two genders. Psychiatric disorders were assessed using a standardized face-to-face diagnostic interview of Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (KSADS-PL), and Body Mass Index (BMI) was measured for each participant. Results: In this study, 22 730 children and adolescents (109 46 boys and 11784 girls), with valid data of BMI, completed the KSADS-PL interview. The prevalence of psychiatric disorders was 21.2% among underweight participants, 22.8% among overweight participants, and 22.2% among obese participants, which was significantly higher than normal weight participants with 19.6% (X2 = 17.55; p = 0.001). In boys' subgroup, depression and separation anxiety were mostly seen among the underweight category, while tic disorder was mostly seen in the obese category. In girls' subgroup, on the other hand, generalized anxiety was mostly observed in the underweight category, while oppositional defiant disorder (ODD), depression, and mental retardation were mostly observed in the obese category. In total, the highest mean BMI rates were among the children and adolescents with alcohol abuse disorder, mania, and panic disorder. However, the lowest BMI rates were among those with attention deficit hyperactivity disorder (ADHD), separation anxiety disorder (SAD), and enuresis. Conclusion: This study gives an overall picture of BMI status in different psychiatric disorders according to gender. Furthermore, in a multidisciplinary approach, the results of this study drew the attention of child psychiatrists to the status of BMI in their clients.
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PMID:Body Mass Index Status across Different Psychiatric Disorders in a National Survey amongst Children and Adolescents: To Identify the Role of Gender. 3207 98


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