Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of fenfluramine on 21 maladaptive behaviors in 20 autistic individuals were examined over a 9-month period utilizing a double-blind, cross-over, placebo-controlled design. Raters carried out time-sampled observations in the school and residence. In addition, videotaped data were collected in controlled settings and assessed by the raters at the conclusion of the study. Some individuals displayed negative side effects such as tension, agitation, insomnia, and sweating during the 16-week period they received fenfluramine. The results demonstrated that fenfluramine caused no significant reductions in maladaptive behaviors. The lack of any significant positive results from this medication and the side effects observed strongly indicate the need for caution in the use of fenfluramine with autistic persons.
J Autism Dev Disord 1987 Sep
PMID:Effects of fenfluramine on autistic individuals residing in a state developmental center. 330 29

Similar clinical and biological features in lethal catatonia (LC) and neuroleptic malignant syndrome (NMS) suggest a relationship between both affections and common physiopathologic mechanisms. Pharmacological effects of several drugs--dopaminergic agonists, benzodiazepines, carbamazepine--suggest an impairment of several systems of neurotransmitters. We report the case of a young woman with infantile psychosis who developed catatonic syndrome worsened by neuroleptic treatment, arising the problem of the chronology of both affections. The evolution with treatment may partially explain the physiopathology. A 18-year old woman with an history of infantile psychosis, experienced insomnia, anorexia, paradoxical agitation developed after affective traumatism (mother's hospitalization). Chlorazepate (150 mg) remained inefficient and hospitalization was necessary. The patient was dumb, prostate in bed. She presented negativism, rigidity of the four limbs, catalepsia and hyperpyrexia (38.5 degrees C). Hepatic transaminases were increased (SGOT: 71 UI/l; N < 30). After cumulated dose of levomepromazine (100 mg) profuse sudation, thermic and cardiovascular instability, alteration of consciousness, major rigidity of limbs appeared. (Blood) hepatic transaminases and muscular enzymes increased. Bacteriological samples, cerebrospinal fluid analysis, CT-scan and EEG were normal. Within 48 hours after rehydratation and bromocriptine (30 mg per day) alteration of consciousness and autonomic disorders decreased but hyperpyrexia (38 degrees C) persisted. Biological parameters were normalized 10 days later. Negativism and psychomotor inertia remained. Lorazepam (3 mg per day) failed to be clinically beneficial. On carbamazepine (600 mg per day) she started speaking and moving spontaneously. Catalepsia disappeared but rigidity and anorexia persisted. Electroconvulsivotherapy (ECT) was necessary. After 2 shocks she started standing up, walking, taking food and speaking fluently.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Acute catatonia and neuroleptic malignant syndrome. A case of infantile psychosis]. 791 82

Family and adoption studies indicate that genetic factors play a role in the development of many psychiatric disorders. A variable number of possible interacting genes giving a predisposition to the diseases is likely. The genetic dissection has been hampered by genetic complexity as well as by difficulties in defining the phenotypes. Genetic mapping efforts using sib pairs, twins and individual large families have revealed preliminary or tentative evidence of susceptibility loci for a number of psychiatric disorders. Illnesses described in this article include the prion disease familial fatal insomnia (FFI), alcoholism, anorexia nervosa, autism, bipolar affective disorder, dyslexia, enuresis nocturna, epilepsia, obsessive-compulsive disorders (OCD), schizophrenia, and the dementias, Alzheimer's disease and frontal lobe dementia. The genes and proteins related to the newly discovered transmitter in the central nervous system, nitric oxide (NO), and its genes and proteins are also reviewed. The number of mapped human genes now exceeds 30,000 of the estimated total number of 60,000 to 100,000 genes. This rapid development will facilitate gene mapping and efforts to isolate and identify the genes responsible for symptom susceptibility in many of the aetiologically unclear psychiatric diseases with complex genetic origin.
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PMID:[Complex hereditary diseases with psychiatric symptoms]. 1010 48

We studied the usefulness of melatonin for sleep disorders and emotional/behavior disturbances of patients with developmental disorders. The efficacy and side effects of melatonin at bedtime were evaluated in 50 children and young adults with sleep disorders (3-28 years old, 41 males and 9 females, autism [AU] in 27 patients, mentally retardation [MR] in 20 patients, and severe motor and intellectual disability [SMID] in 3 patients). The sleep disorders consisted of various types of insomnia in 44 patients and of circadian rhythm sleep disorders in 6 patients. Thirty nine of the insomnia patients and 3 of the circadian rhythm sleep disorder patients experienced improvement in response to melatonin. In some cases, the efficacies were diminished after the daily medication of melatonin. With the emotional/behavior disturbances, excitabilities were often improved in cases whose sleep disorders were also improved. There was almost no change in contrariness, stereotyped behavior and in school/workshop refusal. Melatonin at bedtime was efficacious in 42 of the 50 patients with sleep disorders. In 17 patients, there were side effects (residual drowsiness on the next morning, awakening in the middle of sleep, excitement after awakening and before going to sleep, etc.). But these side effects were not serious. The effects of melatonin were influenced by the type of sleep disturbances, the factors of the environment and the mental conditions. Taking side effects into account, we judged melatonin to be useful in 34 patients.
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PMID:[Usefulness of melatonin for developmental sleep and emotional/behavior disorders--studies of melatonin trial on 50 patients with developmental disorders]. 1048 68

Family and adoption studies indicate that genetic factors play a role in the development of many psychiatric disorders. A variable number of possible interacting genes predisposing to the diseases is likely. The genetic dissection has been hampered by genetic complexity as well as by difficulties in defining the phenotypes. Genetic mapping efforts using sib pairs, twins and individual large families has revealed preliminary or tentative evidence for susceptibility loci for a number of psychiatric disorders. Illnesses include the prion disease familial fatal insomnia (FFI), alcoholism, anorexia nervosa, autism, bipolar affective disorder, dyslexia, enuresis nocturnal, epilepsia, obsessive-compulsive disorders (OCD), schizophrenia, as well as the dementias, Alzheimer's disease and frontal lobe dementia, and mental retardation. The genes and proteins related to the newly discovered transmitter in the central nervous system, nitric oxide (NO), and its genes and proteins are also reviewed. The number of mapped human genes now exceeds 30,000 of the estimated total number of 60,000 to 100,000 genes. This rapid development will facilitate gene mapping, as well as efforts to isolate and identify the genes responsible for symptom susceptibility in many of the etiologically unclear psychiatric diseases with complex genetic origin.
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PMID:[Mental disease a heritage. New genetic knowledge can reveal "public diseases" such as autism, dyslexia, alcoholism, anorexia, schizophrenia]. 1070 80

Asperger syndrome (AS) is a neurodevelopmental disorder belonging to autism spectrum disorders. Both children and adults with AS have subjective impairment in the initiation and continuity of sleep, and studies using objective assessment are sparse. Twenty young AS adults with frequent complaints of low sleep quality were compared to 10 age-, gender- and education-matched controls without sleep complaints using polysomnography and spectral power analysis of slow-wave sleep. AS subjects displayed a similar polysomnographic profile as compared with controls. In spectral power analysis, a statistically nonsignificant trend towards decreased relative delta power and increased theta power in slow-wave sleep was found in the AS group. It seems that nonorganic insomnia, due to anxiety inherent in AS, is responsible for the low sleep quality in these subjects.
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PMID:Sleep in young adults with Asperger syndrome. 1529 69

A growing body of evidence indicates that people with autism frequently experience sleep disorders and exhibit atypical sleep architecture. In order to establish whether sleep disorders truly belong to the autism spectrum disorder (ASD) phenotype, we conducted a subjective and objective study of sleep in a group of high-functioning adults with ASD but without sleep complaints, psychiatric disorders or neurological comorbidity. We compared the subjective data of 27 ASD participants with those of 78 healthy controls matched for chronological age and gender. Subjective measures of sleep in the clinical group were compatible with insomnia and/or a tolerable phase advance of the sleep-wake cycle. Subjective data were confirmed by objective laboratory sleep recordings in a subset of 16 patients and 16 controls. Persons with autism presented with a longer sleep latency (P < 0.04), more frequent nocturnal awakenings (P < 0.03), lower sleep efficiency (P < 0.03), increased duration of stage 1 sleep (P < 0.02), decreased non-REM sleep (stages 2 + 3 + 4, P < 0.04) and slow-wave sleep (stages 3 + 4, P < 0.05), fewer stage 2 EEG sleep spindles (P < 0.004), and a lower number of rapid eye movements during REM sleep (P < 0.006) than did control participants. On clinical scales, the scores of persons with ASD on the Beck Depression Inventory were similar to those of persons without, but their trait anxiety scores on the Spielberger Anxiety Scale were higher (P < 0.02). The state anxiety scores of the Spielberger scale and cortisol levels were the same in the two groups. Objective total sleep time correlated negatively with the Social (-0.52, P < 0.05) and Communication (-0.54, P < 0.02) scales of the Autism Diagnostic Interview-Revised. The sleep of clinical subgroups (10 with high-functioning autism, six with Asperger syndrome) did not differ, except for the presence of fewer EEG sleep spindles in the Asperger syndrome subgroup (P < 0.05). In conclusion, these findings indicate that atypicalities of sleep constitute a salient feature of the adult ASD phenotype and this should be further investigated in younger patients. Moreover, the results are consistent with an atypical organization of neural networks subserving the macro- and microstructure of sleep in ASD. We are furthering this research with quantified analysis of sleep EEG.
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PMID:Atypical sleep architecture and the autism phenotype. 1570 9

In France, psychotropic drugs may be classified in four categories according to their official data. The first category corresponds to psychotropic drugs with an approved indication available in paediatry. Theyare old agents (e.g. haloperidol, amitriptyline, benzodiazepines...) with the exception of methylphenidate (hyperactivity). The second one corresponds to pharmacological agents approved for some indications obtained with adults but not for a1l (i.e. restricted indication: e.g. sertraline approved in paediatry only for OCD but not for depression, risperidone approved only for the treatment of disruptive behaviors in children with subaverage IQs). For the third category, the psychotropic agent is either contraindicated or unadvised under the age of 15 or 18 years, by lack of data (e.g. most of SSRI or atypical antipsychotic drugs). For the last category, official data available in brief summaries offer no information on paediatric use and consequently their administration does not appear possible. Up to now, no approved use has been delivered to injection route (IM or IV) in France, except for an IM formulation of zuclopenthixol. Prescribing psychotropic drug has to respect good practices including close psychological and somatic monitoring that associates the young patient and his relative (psycho-education program). Particular key-points should be taken into consideration (i.e. pharmacokinetic and physiological specificities, risk of false passage under the age of 6 years with capsules or tablets, presence of alcohol in some oral solution or bitter aroma...). Beside these official data, many studies have been published but must be carefully interpreted according to their level of pertinence. Meta-analysis gather all randomised controlled trials published or not, analyse their specific pertinence and thus provide clinically relevant elements. Randomised controlled trials present clinical interest but key-points in study design must be checked (e.g. number of patients, inclusion and exclusion criteria, length of the study and clinical relevance of clinical scales...). Other studies like open trials or clinical cases do not offersufficient guarantees. Some randomised controlled trials of clinical relevance have been carried out in this population with new pharmacological classes (eg SSRI, atypical antipsychotic drugs) and may lead to extended indications in children and adolescents. According to bibliographic and official data, the main criteria in the prescribing choice may take into consideration the following sis stressing a poor benefit/risk ratio. SSRI may offer better prospects but their use has not been approved in this indication, until now. In OCD, sertraline shows great interest to enhance clinical response and represents the molecule of reference. No drug has been approved for mood disorders in children or adolescent, in France, contrary to USA where lithium can be administered over the age of 12 years. In addition, antiepileptic drugs like carbamazepine or divalproate have conducted to clinical improvement in some studies. Benzodiazepines, hydroxyzine and meprobamate use should be strictly restricted in case of anxiety symptoms but are the only agents approved in this indication despise promising results obtained with SSRI. Transitory insomnia may take advantage of alimemazine prescription (approved use over the age of 36 months). Some typical neuroleptics are indicated in tics or in behaviour disorders associated to autism or related syndromes but present clinical limitations and poor tolerability. Promising clinical trials (randomised or not) have been conducted with new atypical antipsychotic drugs like risperidone. In conclusion, present data available for paediatric use of psychotropic agents emphasizes that safety and effectiveness are not always well established in particular for the treatment of chronic disorders (long term tolerability assessment). Moreover, studies should be carried out to specify factors promoting adherence and quality of life for this young population in order to optimise clinical benefit of drug prescription.
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PMID:[Prescription of psychotropic drugs in paediatry: approved indications and therapeutic perspectives]. 1638 15

This study examined sleep patterns, sleep problems, and their correlates in children with autism spectrum disorders (ASD). Subjects consisted of 167 ASD children, including 108 with autistic disorder, 27 with Asperger's syndrome, and 32 with other diagnoses of ASD. Mean age was 8.8 years (SD = 4.2), 86% were boys. Parents completed a self-administered child sleep questionnaire. Results showed that average night sleep duration was 8.9 h (SD = 1.8), 16% of children shared a bed with parent. About 86% of children had at least one sleep problem almost every day, including 54% with bedtime resistance, 56% with insomnia, 53% with parasomnias, 25% with sleep disordered breathing, 45% with morning rise problems, and 31% with daytime sleepiness. Multivariate logistic regression analyses indicated that younger age, hypersensitivity, co-sleeping, epilepsy, attention-deficit/hyperactivity disorder (ADHD), asthma, bedtime ritual, medication use, and family history of sleep problems were related to sleep problems. Comorbid epilepsy, insomnia, and parasomnias were associated with increased risk for daytime sleepiness. Results suggest that both dyssomnias and parasomnias are very prevalent in children with ASD. Although multiple child and family factors are associated with sleep problems, other comorbid disorders of autism may play a major role.
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PMID:Sleep disturbances and correlates of children with autism spectrum disorders. 1700 27

The circadian rhythm of pineal melatonin secretion, which is controlled by the suprachiasmatic nucleus (SCN), is reflective of mechanisms that are involved in the control of the sleep/wake cycle. Melatonin can influence sleep-promoting and sleep/wake rhythm-regulating actions through the specific activation of MT(1) (melatonin 1a) and MT(2) (melatonin 1b) receptors, the two major melatonin receptor subtypes found in mammals. Both receptors are highly concentrated in the SCN. In diurnal animals, exogenous melatonin induces sleep over a wide range of doses. In healthy humans, melatonin also induces sleep, although its maximum hypnotic effectiveness, as shown by studies of the timing of dose administration, is influenced by the circadian phase. In both young and elderly individuals with primary insomnia, nocturnal plasma melatonin levels tend to be lower than those in healthy controls. There are data indicating that, in affected individuals, melatonin therapy may be beneficial for ameliorating insomnia symptoms. Melatonin has been successfully used to treat insomnia in children with attention-deficit hyperactivity disorder or autism, as well as in other neurodevelopmental disorders in which sleep disturbance is commonly reported. In circadian rhythm sleep disorders, such as delayed sleep-phase syndrome, melatonin can significantly advance the phase of the sleep/wake rhythm. Similarly, among shift workers or individuals experiencing jet lag, melatonin is beneficial for promoting adjustment to work schedules and improving sleep quality. The hypnotic and rhythm-regulating properties of melatonin and its agonists (ramelteon, agomelatine) make them an important addition to the armamentarium of drugs for treating primary and secondary insomnia and circadian rhythm sleep disorders.
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PMID:Role of the melatonin system in the control of sleep: therapeutic implications. 1802 Apr 80


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