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PubMed1999

Olanzapine treatment of children, adolescents, and adults with pervasive developmental disorders: an open-label pilot study.

This pilot study examined the efficacy and tolerability of olanzapine in the treatment of children, adolescents, and adults with pervasive developmental disorders (PDDs). Eight patients with principal diagnoses (DSM-IV) of autistic disorder (N = 5) or PDD not otherwise specified (N = 3) were given olanzapine in an open-label, prospective fashion for 12 weeks. Clinical ratings were obtained at baseline and at the end of weeks (EOWs) 4, 8, and 12. Seven of eight patients completed the 12-week trial, and six of the completers were deemed clinical responders as measured by ratings at the EOW 12 of "much improved" or "very much improved" on the global improvement item of the Clinical Global Impression Scale. Significant improvements in overall symptoms of autism, motor restlessness or hyperactivity, social relatedness, affectual reactions, sensory responses, language usage, self-injurious behavior, aggression, irritability or anger, anxiety, and depression were observed. Significant changes in repetitive behaviors were not observed for the group. The EOW 12 mean +/- SD daily dose of olanzapine was 7.8 +/- 4.7 mg/day. The drug was well tolerated with the most significant adverse effects noted to be increased appetite and weight gain in six patients and sedation in three. With respect to weight gain, the mean +/- SD weight for the group increased from 137.50 +/- 55.81 pounds (62.50 +/- 25.37 kilograms) at baseline to 155.94 +/- 55.13 pounds (70.88 +/- 25.06 kilograms) at EOW 12. No evidence of extrapyramidal side effects or liver function abnormalities was seen. These preliminary results suggest that olanzapine may be an effective and well tolerated drug in targeting core and related symptoms of PDDs in children, adolescents, and adults. Further studies, particularly those that are placebo-controlled and double-blinded, are indicated to better define the clinical use of olanzapine in these patient populations.

Adolescent↗
PubMed1998

Reliability and accuracy of differentiating pervasive developmental disorder subtypes.

OBJECTIVE: To evaluate the ability of the DSM-IV criteria for the pervasive developmental disorders (PDD) to reliably and accurately differentiate PDD subtypes. METHOD: The sample consisted of 143 children with various types of developmental disabilities. A diagnosis of PDD and PDD subtype was made by one clinician using information obtained from the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule. The raw data from the Autism Diagnostic Interview-Revised, clinical notes (excluding diagnostic opinion), Autism Diagnostic Observation Schedule, IQ, and other available data were independently assessed by three experienced raters, each of whom then made a separate, blind diagnosis. If there was any disagreement, a consensus best-estimate (CBE) diagnosis was made after discussion. To assess reliability, the agreement between the three raters was calculated using k. Accuracy was assessed by calculating the agreement between the clinician's diagnosis and the CBE and by calculating the error rates associated with the three raters using latent class analysis. RESULTS: The current DSM-IV criteria show good to excellent reliability for the diagnosis of PDD, Asperger's disorder (AsD), and autism, but they show poor reliability for the diagnosis of atypical autism. The clinician (compared to the CBE) had little difficulty differentiating PDD from non-PDD children and autism from AsD but had more difficulty identifying children with atypical autism. The latent class analysis also showed that the average error rates of the three raters for a differentiation of atypical autism from autism were unacceptably high. CONCLUSIONS: Although the psychometric properties of the current DSM-IV criteria for autism and AsD appear quite acceptable, there is likely to be a high rate of misclassification of children given a diagnosis of atypical autism.

Adolescent↗
PubMed2003

A 3-year naturalistic study of 53 preschool children with pervasive developmental disorders treated with risperidone.

BACKGROUND: Only sparse and short-term data are available on pharmacologic treatments in very young children with pervasive developmental disorders (PDD). The purpose of this 3-year naturalistic study (March 1999-April 2002) is to describe the clinical outcome of a consecutive sample of preschool children with PDD treated with risperidone monotherapy. METHOD: The sample consisted of 45 boys and 8 girls aged 3.6 to 6.6 years (mean +/- SD age = 4.6 +/- 0.7 years) with a DSM-IV diagnosis of autistic disorder or PDD, not otherwise specified. Outcome measures included the Children's Psychiatric Rating Scale (CPRS), Clinical Global Impressions-Improvement scale (CGI-I), Children's Global Assessment Scale (CGAS), and a checklist for risperidone side effects. RESULTS: Patients received risperidone for a period ranging from 1 to 32 months (7.9 +/- 6.8 months). Twenty-five patients (47.2%) continued to receive risperidone after the study was completed, while 28 (52.8%) discontinued due to side effects (22.6% [N = 12]), parents' choice (18.9% [N = 10]), lack of efficacy (5.7% [N = 3]), and decision of the treating psychiatrist (5.7% [N = 3]). The optimal dose was 0.55 +/- 0.2 mg/ day. Significant improvement at the last observation was found in CPRS (p < .0001) and CGAS (p < .0001) scores. On the basis of both an improvement of 25% in CPRS score and a score of 1 or 2 on the CGI-I, 46.8% (N = 22) of subjects were considered responders. Behavioral disorders and affect dysregulation were more sensitive to treatment than was interpersonal functioning. Responders received higher doses of medication for a longer period and had a greater weight gain than did nonresponders. Increased prolactin levels without clinical signs (65% [24 of 37]) and increased appetite (15% [8 of 531) were the most frequent side effects. CONCLUSION: These findings suggest that low-dose risperidone may positively affect the clinical outcome in young children with PDD not only in the short-term, but also in the long-term period.

Antipsychotic Agents↗
PubMed2004

The comorbidity of Pervasive Developmental Disorder and Attention Deficit Hyperactivity Disorder: results of a retrospective chart review.

OBJECTIVE: To determine if a sample of children meeting diagnostic criteria for a Pervasive Developmental Disorder (PDD) display symptoms and impairment related to Attention Deficit Hyperactivity Disorder (ADHD) sufficient to warrant a comorbid diagnosis of ADHD. Further, do children with PDD displaying such symptoms demonstrate more impairment in daily life activities than those children only having PDD? METHOD: A retrospective chart review was conducted on children (N = 57) diagnosed with the PDD's of Autism or PDD-Not Otherwise Specified (PDD-NOS), or ADHD. Comparative analysis of questionnaire and neuropsychological test data was completed to determine the severity of ADHD-like symptoms presenting among children with PDD. RESULTS: From the pool of subjects having PDD with sufficient data (N = 27), 7 or 26% met DSM-IV criteria for the combined type of ADHD. Nine or 33% met diagnostic criteria for the Inattentive Type of ADHD and 11 or 41% did not demonstrate a significant number of ADHD symptoms to warrant a comorbid diagnosis of ADHD. Results indicate that a subgroup of children with PDD displaying significant ADHD-like symptoms may in fact have ADHD thus warranting a comorbid diagnosis of ADHD. Current data did not suggest children with PDD and the combined type of ADHD demonstrated significantly more impairment in daily life functioning than those children only having PDD. However, this appeared likely the result of small sample size. The data, however, does indicate such children experience more difficulties in daily situations as rated by parents and teachers. CONCLUSION: These findings reinforce clinical observations indicating that some children with PDD may also experience an independent comorbid condition of ADHD, suggesting that a comorbid diagnosis of ADHD with PDD be considered in such cases. If further findings are replicated, the current exclusionary DSM-IV-TR criteria of making such a comorbid diagnosis should be re-considered.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Etiologic yield of autistic spectrum disorders: a prospective study.

Studies addressing etiologic yield in childhood developmental disabilities have mainly looked at individuals with developmental delay/mental retardation. The few studies addressing the question of etiologic yield in patients with pervasive developmental disorders (PDDs) had a major drawback, in that the enrolled subjects were diagnosed as having the autistic spectrum disorders based only on history and clinical examination, and/or on unspecified instruments. In addition, only some of these patients underwent a complete laboratory evaluation. To investigate the etiologic yield of PDDs, we undertook a large prospective study on subjects selected according to very strict criteria and diagnosed as having PDD based on the present "gold standard" (ADI-R and ADOS-G), and a clinical diagnosis made by a child psychiatrist. Eighty-five (85) patients with PDD and their first degree relatives participated in this study. These patients were selected from a sample of 236 subjects who had received a clinical diagnosis of PDD at the Stella Maris Institute between March 2002 and 2005. Selection criteria for entering the study were: (1) a diagnosis of PDD (with exclusion of the Rett syndrome) confirmed after the administration of the ADI-R (autism diagnostic interview-revised) and the ADOS-G (autism diagnostic observation schedule-generic). In addition, a clinical diagnosis was made by the child psychiatrist, on the basis of presence or absence of DSM-IV symptoms of autism; (2) chronological age between 4 and 18 years; (3) IQ>30; (4) availability of both biologic parents. Patients, 65/85 (76.5%), had autism, 18/85 (21.2%) had PDD-NOS, and the remaining 2/85 (2.3%) had Asperger syndrome. Ages varied between 4 years 2 months and 12 years 5 months (mean 7.6 years), and there was a marked male preponderance (68/85). All subjects underwent various laboratory studies and neuroimaging. With respect to possible etiologic determination, a detailed history and physical examination in this group of patients with PDD was informative in 10.5% (9/85). HRB karyotype was diagnostic in one, and molecular fragile X studies in one child. Brain MRI was informative in two children (2.3%) with relative macrocrania but no neurological features; and EEG was helpful in one child, identifying a Landau-Kleffner disorder. Audiometry and brainstem auditory evoked potentials (BAEPs) showed a bilateral sensorineural loss in another child. Metabolic evaluation gave normal results in all subjects. The results suggest an evaluation paradigm with reference to etiologic determination for individuals with PDDs that does not presently justify metabolic or neuroimaging on a screening basis. Recurrence risk, treatment implications, and significant and long-lasting emotional relief for the parents suggest that serious consideration be given to clinical genetic examination, genetic testing, EEG study (during wakefulness and sleep), and audiometry, despite a relatively low yield.

Adolescent↗
PubMed2005

The presentation of anxiety in children with pervasive developmental disorders.

OBJECTIVE: Although the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnostic criteria generally discourage the diagnosis of other Axis I disorders in children with pervasive developmental disorder (PDD), anxiety symptoms are often observed in this clinical population. Moreover, there are some albeit limited data that suggest an association between anxiety and psychotic symptoms in children. Because co-occurring psychiatric symptoms have important clinical implications, this study examined anxiety and psychotic symptoms in children with and without PDD. METHOD: Parents and teachers completed the Early Childhood Inventory-4 (ECI-4) or the Child Symptom Inventory (CSI-4) for children evaluated in a developmental disabilities clinic (PDD) or a child psychiatry outpatient clinic (non-PDD). Children were divided into four groups: 3-5- year-olds with (n = 182) and without (n = 135) PDD, and 6-12-year-olds with (n = 301) and without (n = 191) PDD. The 6-12-year-olds were further divided into high-anxious and low-anxious subgroups based on CSI-4 ratings and compared with regard to severity of psychotic symptoms. RESULTS: Teachers rated preschoolers with PDD as exhibiting more severe anxiety symptoms than the non-PDD group; however, the converse was true for parent ratings. For 6-12- year-olds, both parents and teachers rated children with PDD as significantly more anxious than non-PDD clinic referrals. In general, the severity of anxiety symptoms varied by PDD subtype (Asperger's disorder > PDDNOS > Autistic disorder) and IQ (high > low). Furthermore, highly anxious 6-12-year-olds with PDD received significantly higher parent and teacher ratings of psychotic symptom severity (strange behaviors, hearing voices, illogical thinking, inappropriate affect, and odd thoughts) than our low-anxious group, even when controlling for PDD symptom severity. Moreover, the relation between anxiety level and psychotic symptom severity was similar for both PDD and non-PDD children. Parent and teachers differed in their perceptions of the severity of specific anxiety symptoms. In addition, parent- versus teacher-defined anxiety level groups varied with regard to the differential severity of psychotic symptoms. This finding highlights the importance of continued investigation of source-specific syndromes in children with PDD. Two case vignettes are presented. CONCLUSION: Anxiety appears to be a clinically important concern in many children with PDD. Similarities in anxiety symptom presentation and their association with psychotic symptoms in both children with and without PDD support the possibility of: (1) psychiatric comorbidity in the former; (2) at least some overlap in causal mechanisms for anxiety and psychotic symptoms in both PDD and non-PDD children; and (3) a unique diagnostic entity comprised of PDD, anxiety, and psychotic symptoms. Lastly, clinicians should seriously consider dual diagnoses in children with PDD.

Anxiety Disorders↗
PubMed2003

Use of psychotropic agents in preschool children: associated symptoms, diagnoses, and health care services in a health maintenance organization.

BACKGROUND: Recent pharmacoepidemiological reports have contributed to concerns about frequent and perhaps indiscriminate psychopharmacotherapy for very young children. OBJECTIVE: To examine the diagnoses, symptoms, and health care services associated with preschool children receiving psychotropic medication. DESIGN: Population-based pharmacoepidemiological analysis of electronic medical records, paper medical and mental health charts, and pharmacy records from 1997 and 1998. SETTING: A large Pacific Northwest health maintenance organization. PARTICIPANTS: Preschool children receiving psychotropic medication (psychostimulants, antidepressants, neuroleptics, or alpha(2)-adrenergic agonists). MEASURES: Physician-reported mental health diagnoses and related symptoms, functional impairment, family and participant characteristics, and the types and level of associated medical and mental health services. RESULTS: Of 743 preschool children who clinicians identified as having behavioral or emotional problems, 120 (16%) received psychotropic medication; 57 children (48%) were prescribed a stimulant medication only, and 60 (50%) received a diagnosis of attention-deficit/hyperactivity disorder. Most children had substantial psychosocial risk factors, including parents with psychiatric or substance abuse problems (71%; n = 85), documented histories of abuse (29%; n = 35), and out-of-home placement (31%; n = 37). Four of 5 children or families (83%; n = 99) received psychosocial services in addition to pharmacotherapy. On average, children received psychotropic medication at least 6 months after initial identification of a behavioral or mental health problem. CONCLUSIONS: Despite commentary by the popular media about widespread psychopharmacotherapy for very young children, such treatment was only infrequently received in this health plan. Most children receiving psychopharmacotherapy had substantial additional risk factors and were receiving psychosocial services for mental health or behavioral management.

Attention Deficit and Disruptive Behavior Disorder↗
PubMed1977

Neurobiologic antecedents of schizophrenia in children. Evidence for an inherited, congenital neurointegrative defect.

In chronic schizophrenics, disordered motor development in childhood is followed by more early cognitive and social impairment and poorer outcome; childhood schizophrenics represent the most extreme variants of this. Preschizophrenic infants show a fluctuating dysregulation of maturation--or "pandevelopmental retardation" (PDR)--that involves physical growth; gross motor, visual-motor, and cognitive development; proprioceptive and vestibular responses; muscle tone; and possibly arousal. Pandevelopmental retardation was significantly related to a genetic history for schizophrenia (less than .05), but not to obstetric complications. The severity of PDR was significantly related to the severity of later psychiatric and cognitive disorder (less than .01). Pandevelopmental retardation provides a "marker" in infancy for the inherited neurointegrative defect in schizophrenia. These disordered functions should be studied by anyone interested in the biology of the schizophrenic genotype or in specific early interventions for children at risk.

Adult↗
PubMed2002

Evidence for early-childhood, pan-developmental impairment specific to schizophreniform disorder: results from a longitudinal birth cohort.

BACKGROUND: Childhood developmental abnormalities have been previously described in schizophrenia. It is not known, however, whether childhood developmental impairment is specific to schizophrenia or is merely a marker for a range of psychiatric outcomes. METHODS: A 1-year birth cohort (1972-1973) of 1037 children enrolled in the Dunedin Multidisciplinary Health and Development Study was assessed at biennial intervals between ages 3 and 11 years on emotional, behavioral, and interpersonal problems, motor and language development, and intelligence. At age 11 years, children were asked about psychotic symptoms. At age 26 years, DSM-IV diagnoses were made using the Diagnostic Interview Schedule. Study members having schizophreniform disorder (n = 36 [3.7%]) were compared with healthy controls and also with groups diagnosed as having mania (n = 20 [2%]) and nonpsychotic anxiety or depression disorders (n = 278 [28.5%]) on childhood variables. RESULTS: Emotional problems and interpersonal difficulties were noted in children who later fulfilled diagnostic criteria for any of the adult psychiatric outcomes assessed. However, significant impairments in neuromotor, receptive language, and cognitive development were additionally present only among children later diagnosed as having schizophreniform disorder. Developmental impairments also predicted self-reported psychotic symptoms at age 11 years. These impairments were independent of the effects of socioeconomic, obstetric, and maternal factors. CONCLUSIONS: The results provide evidence for an early-childhood, persistent, pan-developmental impairment that is specifically associated with schizophreniform disorder and that predicts psychotic symptoms in childhood and adulthood.

Adolescent↗
PubMed1994

Evaluation of school children at high risk for fragile X syndrome utilizing buccal cell FMR-1 testing.

We describe a pilot project utilizing saliva to identify the FMR-1 mutation in high-risk special education students from four public school districts in Colorado. The program included presentations to special education teachers regarding fragile X syndrome, parental consent for testing, completion of a behavior checklist by the teachers, identification of special education students at high risk for fragile X syndrome, subsequent brief examination of face and hands, collection of a saliva sample by either Gatorade swish or brushing of the inside of the cheek, and analysis for the FMR-1 mutation by PCR. Equivocal samples were studied by direct DNA testing using Southern blot analysis, and abnormal results were confirmed by a blood analysis for the FMR-1 mutation. Mutant individuals received genetic counseling and medical and educational assessments to optimize treatment and intervention. This pilot project was met with enthusiasm by the schools. Of the first 439 students evaluated, 68% were male with an average age of 7.75 years; 13% were mentally retarded or autistic. Most students referred for the evaluation were learning disabled (51%) and/or had an Attention Deficit Hyperactivity Disorder (ADHD) (35%). The overall prevalence of the FMR-1 mutation was 5 of 439 or 1.1%. This relatively low yield is probably due to the high number of non-retarded but learning disabled students tested. Of the mentally retarded patients tested, 3.5% were positive for the FMR-1 mutation; however, of the non-retarded or learning disabled patients, only 0.79% were FMR-1 positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2006

The yield of subtelomeric FISH analysis in the evaluation of autistic spectrum disorders.

To assess the frequency of cryptic subtelomeric rearrangements in children and adolescents with autism spectrum disorders, blood samples were studied using a complete set of subtelomeric FISH probes in 72 children with autism spectrum disorders. All children had normal high resolution karyotype, DNA fra-X analysis, brain MRI, metabolic work-up, and physical/neurological examination. Subtelomeric analysis did not detect abnormalities in any of the subjects, suggesting the uselessness of such investigations in individuals with primary autism spectrum disorders.

Child↗
PubMed1996

Outcome of short-term child psychiatric hospitalization: teacher evaluation at 5-month and 12-month follow-up.

This prospective follow-up study reports the outcome of children and adolescents discharged from short-term inpatient treatment based on teacher evaluations with Rutter's Questionnaire. There was a significant reduction in deviant behaviour between pretreatment and 5-month follow-up assessment but not between 5-month and 1-year follow-up. However, relatively few children fell within the normal range of non-clinically referred children. The child's more impaired general functioning, more frequent individual behaviour symptoms, antisociality and disengaged family interaction were associated with less favourable outcome. Pure affective or anxiety disorder predicted functioning within normal range and improvement in behaviour problems at follow-up. Treatment variables were not found to be associated with the outcome.

Adolescent↗
PubMed1982

Effects of vestibular stimulation on motor development and stereotyped behavior of developmentally delayed children.

Four developmentally delayed babies were given semicircular canal stimulation in an effort to facilitate their motor and reflex development. Each of the children also exhibited abnormal stereotyped movements. The theory was advanced that these movements are related to motor development and that significant improvements in motor abilities will produce changes in the intensity and/or form of stereotypic responding. Semicircular canal stimulation was provided by rotating the children in a motor-driven chair at a velocity of about 17 rpm for 10 minutes daily over a period of 2 weeks. Standard motor and reflex measures were taken before, during, and after the rotation treatment period. Daily observations were made of the children's stereotyped movements. Over the course of the study all of the children showed motor and/or reflex changes that were attributable to the vestibular stimulation. In addition, some evidence was obtained linking changes in stereotypic responding to the vestibular stimulation.

Arousal↗
PubMed1993

The criterion-related validity of the Childhood Autism Rating Scale and the Autism Behavior Checklist.

The present study sought to examine the relationship between two popular instruments for screening autistic children: the Childhood Autism Rating Scale (CARS) and the Autism Behavior Checklist (ABC). The sample included 77 individuals. The records of 48 subjects contained firm diagnoses of autism, while the suggestion of autism was found in the remaining records. Correlations between the two scales ranged from -.16 to .73 (median = .39). The validity coefficient between the two total scores was .67. Using cutoff scores recommended by the authors, an analysis of the sensitivity of the two instruments was conducted. The CARS correctly identified 98% of the autistic subjects; it identified 69% of the possibly autistic as autistic. The ABC correctly identified 88% of the autistic subjects, while it identified 48% of those subjects considered possibly autistic as autistic. A phi coefficient was computed to estimate the degree of relationship between the nominal classifications produced by the two instruments. A moderate relationship was found (r phi = .54). Implications of the results are discussed.

Adolescent↗
PubMed1993

A comparison between the handicaps behaviour and skills schedule and the psychoeducational profile.

Comparisons were made of developmental scores (administered with the Psychoeducational Profile [PEP] and the Handicaps Behaviour and Skills Schedule [HBS] for a group of 72 children ages 23 to 148 months. All children had been referred to the Centre of Autism in Leiden, the Netherlands. This Centre is a collaboration between the University clinic of special education and the regional health service. Forty-five children were diagnosed as autistic and 27 as nonautistic but suffering from another disorder. In this study, the correlation between the two instruments is higher than expected, in particular for the group of autistic children (.83). The internal consistency of the subscales of the PEP and the HBS are overall very satisfactory. The Cronbach's alphas of the PEP scales vary from .79 to .96 for the total group and from .77 to .95 for the autistic group. The alphas for the HBS vary from .74 to .92 for the total group and from .20 to .87 for the autistic group, there is one alpha at .20, the rest are .60 or higher.

Autistic Disorder↗