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PubMed2006

Neurobehavioral disorders in children, adolescents, and young adults with Down syndrome.

The term dual-diagnosis refers to a person with mental retardation and a psychiatric disorder. Most children with Down syndrome (DS) do not have a psychiatric or neurobehavioral disorder. Current prevalence estimates of neurobehavioral and psychiatric co-morbidity in children with DS range from 18% to 38%. We have found it useful to distinguish conditions with a pre-pubertal onset from those presenting in the post-pubertal period, as these are biologically distinct periods each with a unique vulnerability to specific psychiatric disorders. Due to the increased recognition that psychiatric symptoms may co-occur with mental retardation, and are not inextricably linked to cognitive impairment, these conditions are considered treatable, in part, under a medical model. Improvement in physiologic regulation, emotional stability, and neurocognitive processing is one of the most elusive but fundamental goals of pharmacologic intervention in these disorders.

Adolescent↗
PubMed2006

Variation in vocal-motor development in infant siblings of children with autism.

In this study we examined early motor, vocal, and communicative development in a group of younger siblings of children diagnosed with autism (Infant Siblings). Infant Siblings and no-risk comparison later-born infants were videotaped at home with a primary caregiver each month from 5 to 14 months, with follow-up at 18 months. As a group, Infant Siblings were delayed in the onset of early developmental milestones and spent significantly less time in a greater number of postures, suggestive of relative postural instability. In addition, they demonstrated attenuated patterns of change in rhythmic arm activity around the time of reduplicated babble onset; and they were highly likely to exhibit delayed language development at 18 months.

Autistic Disorder↗
PubMed2001

Alleviation of sleep disturbance and repetitive behavior by a selective serotonin re-uptake inhibitor in a boy with Asperger's syndrome.

An 8 year-old boy with Asperger's syndrome had difficulties in communicating with his teachers and classmates. He occasionally stole out of the classroom. He could not sleep at night recalling his awful experience and kept crying every night and refused to go to school. The treatment with fluvoxamine was started at the dose of 25 mg daily. Four weeks after the treatment, his repetitive behavior and hyperactivity decreased and night crying diminished. Although he still has difficulties in communicating with others, he is now able to attend extra-curricular classes in a private school. Fluvoxamine, a selective serotonin re-uptake inhibitor that has been mainly used for patients with depression and obsessive-compulsive disorder, might be effective for compulsive symptoms and sleep disturbance of patients with pervasive developmental disorders.

Asperger Syndrome↗
PubMed2001

Rett syndrome in Spain: mutation analysis and clinical correlations.

Rett syndrome (RTT) is an X-linked neurodevelopmental disease that affects girls almost exclusively. In a high proportion of patients the disease is caused by de novo mutations at the MECP2 gene, encoding methyl-CpG-binding protein 2. With the aim to characterize the spectrum of mutations in a series of sporadic RTT patients, including an affected male, and to relate the genetic results to the clinical features of the disease, a clinical checklist and a score system were elaborated to evaluate the clinical severity of the disease. Mutation analysis of the MECP2 coding region was done by direct sequencing. De novo mutations were found in 60% of the patients, including both classic and atypical forms. The change R133H was identified in a 13-year-old boy showing a classic RTT phenotype and normal karyotype. Significant differences were observed among missense and truncating mutations regarding disease severity, age of onset of stereotypies, and the ability of the patients to sit alone and to walk.

Adolescent↗
PubMedDate not supplied

Body-rocking in college students and persons with mental retardation: characteristics, stability, and collateral behaviors.

Body-rocking was analyzed in four studies. The first showed that rocking chairs are not necessarily preferred by people with mental retardation, and that a rocking chair produces a higher amplitude of body-rocking. A second study demonstrated the stability of various measures of body-rocking over a 21-month period. Stable idiosyncratic behaviors accompanying body-rocking also were described. The third study showed that, when compared with college students who engage in habitual body-rocking, persons with mental retardation engage in more body-rocking than college students on various dimensions, and that they also show different collateral behaviors. Finally, in the fourth study, a reanalysis of the data from Study I showed that collateral behaviors do not necessarily occur as part of a body-rocking complex.

Adult↗
PubMed2002

Fringe phenotypes in autism: a review of clinical, biochemical and cognitive studies.

Progress in identifying the genetic vulnerability factors in autism requires correct identification of the inherited phenotype(s). This can be achieved not only by the accurate description of the affected subject but also by the identification of vulnerability traits in non-affected relatives of autistic probands. This review will focus on this last strategy and principally on clinical, biochemical and cognitive traits.

Autistic Disorder↗
PubMed2003

Behavioral comparisons in autistic individuals from multiplex and singleton families.

Autistic disorder (AD) is a complex neurodevelopmental disorder. The role of genetics in AD etiology is well established, and it is postulated that anywhere from 2 to 10 genes could be involved. As part of a larger study to identify these genetic effects we have ascertained a series of AD families: Sporadic (SP, 1 known AD case per family and no known history of AD) and multiplex (MP, > or = 2 cases per family). The underlying etiology of both family types is unknown. It is possible that MP families may constitute a unique subset of families in which the disease phenotype is more likely due to genetic factors. Clinical differences between the two family types could represent underlying genetic heterogeneity. We examined ADI-R data for 69 probands from MP families and 88 from SP families in order to compare and contrast the clinical phenotypes for each group as a function of verbal versus nonverbal status. Multivariate analysis controlling for covariates of age at examination, gender, and race (MANCOVA) revealed no differences between either the verbal or nonverbal MP and SP groups for the three ADI-R area scores: social interaction, communication, and restricted/repetitive interests or behaviors. These data failed to find clinical heterogeneity between MP and SP family types. This supports previous work that indicated that autism features are not useful as tools to index genetic heterogeneity. Thus, although there may be different underlying etiologic mechanisms in the SP and MP probands, there are no distinct behavioral patterns associated with probands from MP families versus SP families. These results suggests the possibility that common etiologic mechanisms, either genetic and/or environmental, could underlie all of AD.

Autistic Disorder↗
PubMed1998

Distinctiveness and correlates of maladaptive behaviour in children and adolescents with Smith-Magenis syndrome.

This two-part study examines the distinctiveness and correlates of maladaptive behaviour in 35 children and adolescents with Smith-Magenis syndrome, a developmental disorder caused by an interstitial deletion of chromosome 17 (p11.2). Study I compares Child Behavior Checklist scores in 35 children with Smith-Magenis syndrome to age- and gender-matched subjects with Prader-Willi syndrome and mixed intellectual disability. Subjects with Smith-Magenis syndrome had significantly higher levels of maladaptive behaviour than the other groups. Although some problems were shared across groups, 12 behaviours differentiated the three groups with 100% accuracy. Study 2 assessed the frequency and correlates of self-injurious and stereotypical behaviours, including unusual features such as nail-yanking, inserting objects into bodily orifices, self-hugging and a 'lick-and flip' behaviour. Nail-yanking and bodily insertions were less common than other types of self-injury, and self-hugs and the 'lick-and flip' stereotypies were seen in about half the sample. Although age and degree of delay were correlated with problem behaviours, sleep disturbance emerged as the strongest predictor of maladaptive behaviour. The implications are discussed for clinical diagnostic ambiguities between the Smith-Magenis and Prader-Willi syndromes, and for intervention.

Adolescent↗
PubMed2004

Attention orienting by another's gaze direction in children with autism.

BACKGROUND: The aim of this study was to investigate attention orienting triggered by another's gaze direction in autism. METHOD: Twelve high-functioning children with autism and gender- and age-matched normal control children were studied using two tasks. In the first task, children were asked to detect laterally presented target stimuli preceded by centrally presented facial cue stimuli in which gaze was either straight ahead or averted. The direction of the cue was either congruent, neutral, or incongruent with respect to the laterality of the target stimulus. In the second task, children were asked to discriminate the direction of eye gaze. RESULTS: The results showed that another person's static gaze direction triggered an automatic shift of visual attention, both in children with autism and in normally developing children. The children in both groups were also able to overtly discriminate the direction of the gaze. CONCLUSION: These results seem to suggest that, in children with autism, the visual system processes information about another person's gaze direction and sends this information to those areas that subserve reflexive attention orienting. However, future studies are needed to investigate whether the processing of eyes and gaze direction relies on similar neural mechanisms in children with autism and in normally developing children.

Attention↗
PubMed1998

Behavioural effects of long-term multi-sensory stimulation.

OBJECTIVES: Regular access to a multi-sensory environment (MSE or Snoezelen room) was compared with a non-complex sensory environment for individuals with learning disabilities. We also tested the prediction that those individuals whose challenging behaviour was maintained by sensory consequences would benefit most from exposure to the MSE. DESIGN: The conditions were compared over 16-week periods using a double crossover design, and were matched for social contact and attention from the enabler. Participants were randomly assigned to orders of treatments. METHODS: Participants were 27 adults with severe/profound learning disabilities who exhibited challenging behaviour. Behaviour was assessed before and after each treatment phase using both direct observation and standardized assessments (the Functional Performance Record and the Problem Behaviour Inventory). The behavioural observations formed the basis of a functional analysis of each individual's challenging behaviour. RESULTS: Some participants became more calm and relaxed while in the MSE, however, the objective measures of behaviour outside the treatment settings revealed no difference between the MSE and control conditions. Challenging behaviour maintained by sensory consequences showed no greater responsivity to the MSE than to the control condition. CONCLUSIONS: The multi-sensory environment had no effects beyond those that could be ascribed to the social interaction between participant and enabler. Anecdotal evidence of favourable responses within the MSE itself could not be confirmed outside the environment.

Adult↗
PubMed2005

On the pharmacotherapy of sleep bruxism: placebo-controlled polysomnographic and psychometric studies with clonazepam.

OBJECTIVES: Sleep bruxism (SB) is a parasomnia defined as a stereotyped movement disorder characterized by grinding or clenching of the teeth during sleep. Pathophysiologically, SB is the result of biological and psychosocial influences. Treatment comprises behavioral, orthodontic and pharmacological interventions. While benzodiazepines and muscle relaxants have been reported by clinicians to reduce bruxism-related motor activity, placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate the acute effects of clonazepam (Rivotril) as compared with placebo, utilizing polysomnography and psychometry. METHOD: Ten drug-free outpatients (6 females, 4 males), aged 46.5 +/- 13.1 years, suffering from SB (ICD-10: F45.8; ICSD: 306.8) and having been treated by bite splints were included in the trial. Comorbidity was high: 7 patients presented nonorganic insomnia related to adjustment or anxiety disorders (5 patients) or depression (2 patients); all patients had a concomitant movement disorder (6 restless legs syndrome, 4 periodic leg movement disorder). After one adaptation night, patients received placebo and 1 mg clonazepam 1/2 hour before lights out in a single-blind, nonrandomized study design. Objective sleep quality was determined by polysomnography, subjective sleep and awakening quality by rating scales, objective awakening quality by psychometric tests. Clinical evaluation was based on the Pittsburgh Sleep Quality Index (PSQI), the Zung Depression (SDS) and Anxiety (SAS) Scales, the Quality of Life Index, the Epworth Sleepiness Scale and the International Restless Legs Syndrome Study Group (IRLSSG) Scale. RESULTS: On admission, SB patients exhibited deteriorated PSQI, SAS, SDS and IRLSSG measures. As compared with placebo, 1 mg clonazepam significantly improved the mean bruxism index from 9.3 to 6.3/h of sleep. Furthermore, it significantly improved the total sleep period, total sleep time, sleep efficiency, sleep latency and time awake during the total sleep period, and increased stage 2 sleep and movement time. Periodic leg movements decreased significantly, while the apnea index and apnea-hypopnea index increased marginally, but remained within normal limits. Subjective sleep quality improved as well, while in mood, performance and psychophysiology no changes were observed. CONCLUSION: Acute clonazepam therapy significantly improved not only the bruxism index but also objective and subjective sleep quality, with unchanged mood, performance and psychophysiological measures upon awakening, suggesting good tolerability of the drug.

Adult↗
PubMed1989

Recognition and differential diagnosis of tardive dyskinesia.

Tardive dyskinesia (TD) is a consequence of chronic neuroleptic therapy. It is an irregular stereotyped movement disorder that is usually choreic in appearance, and is subject to temporary volitional control. Dystonia, akathisia, and tics are uncommon variants of the classic tardive syndrome. Characteristic clinical features including amelioration by action, augementation by distraction, partial volitional suppressibility, and lack of subjective distress help differentiate TD from other movement disorders such as resting tremor, Huntington's disease, spontaneous dyskinesias, and abnormal movements accompanying psychiatric illnesses.

Antipsychotic Agents↗
PubMed1999

Self-injurious skin picking: clinical characteristics and comorbidity.

BACKGROUND: Repetitive skin picking, a self-injurious behavior that may cause severe tissue damage, has received scant empirical attention. The authors examined the demographics, phenomenology, and associated psychopathology in a series of 31 subjects with this problem. METHOD: Subjects were administered the Structured Clinical Interview for DSM-IV for Axis I and Axis II disorders. They also completed several mood questionnaires and a new self-report inventory designed to assess phenomenology, triggers, cognitions, emotions, and consequences associated with skin picking. RESULTS: The mean age at onset on self-injurious skin picking was 15 years, and the mean duration of illness was 21 years. All subjects picked at more than one body area, and the most frequent sites of skin picking were pimples and scabs (87%). The most common comorbid Axis I diagnoses were obsessive-compulsive disorder (OCD; 52%), alcohol abuse/dependence (39%), and body dysmorphic disorder (32%). Forty-eight percent (N = 15) of the subjects met criteria for at least one mood disorder, and 65% (N = 20) for at least one anxiety disorder. The most common Axis II disorders were obsessive-compulsive personality disorder (48%) and borderline personality disorder (26%). CONCLUSION: Self-injurious skin picking is a severe and chronic psychiatric and dermatologic problem associated with high rates of psychiatric comorbidity. It may be conceptualized as a variant of OCD or impulse-control disorder with self-injurious features and may, in some cases, represent an attempt to regulate intense emotions.

Adolescent↗
PubMed1994

Fatal neurotoxicity of arteether and artemether.

Artemisinin (qinghaosu) and several derivatives have been developed and are in use as antimalarial drugs but scant information is available regarding animal or human toxicity. Following a eight-day, multiple-dose, pharmacokinetic study of arteether (AE) (10 mg/kg/day [n = 6] and 20 mg/kg/day [n = 6]) in dogs, all high-dose animals displayed a progressive syndrome of clinical neurologic defects with progressive cardiorespiratory collapse and death in five of six animals. Neurologic findings included gait disturbances, loss of spinal and pain response reflexes, and prominent loss of brain stem and eye reflexes. Animals had prolongation of QT interval corrected for rate (QTc) on electrocardiograms (ECGs) with bizarre ST-T segment changes. Prominent neuropathic lesions were noted to be primarily limited to the pons and medulla. Similar lesions with dose-related severity were noted in eight other dogs studied in a second study with intramuscular (IM) administration of AE in sesame oil during a 28-day, dose-ranging study using 5, 10, 15, and 20 mg/kg/day. Injury, graded by a pathologist blinded to the dose group, showed a dose-related, region-specific injury in all animals that was most pronounced in the pons. Further studies in Sprague-Dawley rats using IM administration of AE and artemether (AM) at a dose of 12.5-50 mg/kg/day for 28 days confirmed the onset of a clinical neurologic syndrome with dose-related changes in body weight, activity, and seizure-like activity, stereotypic movement disorders, and ECG changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Akathisia in adults with mental retardation: development of the Akathisia Ratings of Movement Scale (ARMS).

We developed an akathisia rating scale for use with persons who have mental retardation and screened for the occurrence of akathisia in three samples: 66 adults receiving maintenance neuroleptic treatment, 20 adults not receiving neuroleptics, and 8 adults undergoing neuroleptic dose reduction. The scale had an acceptable level of interrater reliability and validly measured group differences related to neuroleptic treatment status. Using an empirically derived cut-off-score, we estimated the prevalence rate for akathisia to be 5% in neuroleptic-free subjects, 17% in neuroleptic-maintenance subjects, and 25% in neuroleptic-reduction subjects. Akathisia, dyskinesia, and stereotypy manifested as qualitatively different movement topograhies. The occurrence of dyskinesia stereotyped movement disorder was associated significantly with an increased occurrence of akathisia.

Adolescent↗
PubMed1997

Boys with Asperger's disorder, exceptional verbal intelligence, tics, and clumsiness.

Five boys with both Asperger's disorder and Tourette syndrome, exceptional verbal intelligence, and clumsiness are reported. Each presented at early elementary school age with a prominent complaint of social difficulties with peers. History was notable for a flapping stereotypy and the neurological examination revealed motor and/or vocal tics and numerous motor soft signs. Highly specialized interests were characteristics. Language prosody and/or pragmatics was impaired. Despite exceptional verbal intelligence, the children were not, according to their teachers and parents, faring well either socially or academically. Motor difficulties, manifested psychometrically as a significant performance IQ disadvantage, interfered with school performance and social adjustment. Tics, although not noted by parents in the clinical history, compounded their social difficulties. Asperger's disorder in these highly verbal children overlaps with pervasive developmental disorder (PDD) on account of the socioemotional difficulties and stereotypies seen in both. Asperger's disorder and Tourette syndrome overlap in these children on account of the tics. Finally, Asperger's disorder and the right-hemisphere-based learning disorders overlap on account of the visuoperceptual and attentional deficits that can occur in both.

Child, Preschool↗