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1.
Pharmacol Ther. 2018 May 12. pii: S0163-7258(18)30087-1. doi: 10.1016/j.pharmthera.2018.05.007. [Epub ahead of print]

Autism Spectrum Disorder: Classification, diagnosis and therapy.

Author information

1
Department of Psychiatry, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
2
Department of Psychiatry and Psychotherapy, Kutvolgyi Clinical Centre, Semmelweis University, Kutvolgyi ut 4, 1125 Budapest, Hungary.
3
Department of Psychiatry and Neuroscience Program, , Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA. Electronic address: ftarazi@hms.harvard.edu.

Abstract

Autism Spectrum Disorder (ASD) refers to a group of neurodevelopmental disorders including autism, Asperger's syndrome (AS) and pervasive developmental disorder-not otherwise specified (PDD-NOS). The new diagnostic criteria of ASD focuses on two core domains: social communication impairment and restricted interests/repetitive behaviors. The prevalence of ASD has been steadily increasing over the past two decades, with current estimates reaching up to 1 in 36 children. Hereditary factors, parental history of psychiatric disorders, pre-term births, and fetal exposure to psychotropic drugs or insecticides have all been linked to higher risk of ASD. Several scales such as the Childhood Autism Rating Scale (CARS), The Autism Spectrum Disorder-Observation for Children (ASD-OC), The Developmental, Dimensional, and Diagnostic Interview (3di), are available to aid in better assessing the behaviors and symptoms associated with ASD. Nearly 75% of ASD patients suffer from comorbid psychiatric illnesses or conditions, which may include attention-deficit hyperactivity disorder (ADHD), anxiety, bipolar disorder, depression, Tourette syndrome, and others. Both pharmacological and non-pharmacological interventions are available for ASD. Pharmacological treatments include psychostimulants, atypical antipsychotics, antidepressants, and alpha-2 adrenergic receptor agonists. These medications provide partial symptomatic relief of core symptoms of ASD or manage the symptoms of comorbid conditions. Non-pharmacological interventions, which show promising evidence in improving social interaction and verbal communication of ASD patients, include music therapy, cognitive behavioral therapy and social behavioral therapy. Hormonal therapies with oxytocyin or vasopressin receptor antagonists have also shown some promise in improving core ASD symptoms. The use of vitamins, herbal remedies and nutritional supplements in conjunction with pharmacological and behavioral treatment appear to have some effect in symptomatic improvement in ASD, though additional studies are needed to confirm these benefits. Developing novel disease-modifying therapies may prove to be the ultimate intervention for sustained improvement of symptoms in ASD.

KEYWORDS:

Asperger's syndrome; Autism; Cognitive behavioral therapy; Comorbid disorders; Music therapy; Pervasive developmental disorder

Publication type

Publication type

2.
J Child Adolesc Psychopharmacol. 2017 Jun;27(5):413-421. doi: 10.1089/cap.2016.0146. Epub 2017 Mar 27.

Repetitive Transcranial Magnetic Stimulation for the Treatment of Executive Function Deficits in Autism Spectrum Disorder: Clinical Trial Approach.

Author information

1
1 Centre for Brain and Mental Health, The Hospital for Sick Children , Toronto, Canada .
2
2 The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Campbell Family Mental Health Research Institute, The Centre for Addiction and Mental Health, University of Toronto , Toronto, Canada .
3
3 Department of Psychiatry, Faculty of Medicine, University of Toronto , Toronto, Canada .
4
4 Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute , Centre for Addiction and Mental Health, Toronto, Ontario, Canada .
5
5 Genetics and Genome Biology and Autism Research Unit, The Centre for Applied Genomics, The Hospital for Sick Children , Toronto, Canada .
6
6 Program in Neurosciences and Mental Health, Research Institute , The Hospital for Sick Children, Toronto, Canada .
7
7 Department of Psychology, Faculty of Graduate Studies, University of Toronto , Toronto, Canada .
8
8 Division of Child and Adolescent Psychiatry, Department of Psychiatry and Psychology, Mayo Clinic , Rochester, Minnesota.

Abstract

OBJECTIVE:

Executive function (EF) deficits in patients with autism spectrum disorder (ASD) are ubiquitous and understudied. Further, there are no effective, neuroscience-based treatments to address this impairing feature of ASD. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in addressing EF deficits in adult neuropsychiatric disorders. This article will outline the design of a novel randomized-controlled trial of bilateral, 20 Hz, rTMS applied to the dorsolateral prefrontal cortex (DLPFC) for treatment of EF deficits in ASD that is currently ongoing. We describe prior therapeutic rTMS research for ASD and prior rTMS trials targeting EFs in adult neuropsychiatric disorders. A neurophysiological rationale for rTMS treatment of EF deficits in ASD is presented.

METHODS:

An ongoing protocol will enroll participants aged 16-35 with ASD and no intellectual disability. Psychotropic medications will be continued during the 4-week trial of active 20 Hz versus sham rTMS applied to the DLPFC. Twenty, active treatment sessions consisting of 25 stimulation trains at a 90% motor threshold will be administered. The primary outcome measure is the Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial working memory task. At present, recruitment, enrollment, and treatment within the described clinical trial are ongoing.

CONCLUSIONS:

EF deficits are common and impairing symptoms of ASD. There are no evidence-based treatments for EF deficits in ASD. The protocol described here will provide important preliminary data on the feasibility and efficacy of 20 Hz rTMS to DLPFC for EF deficits in ASD.

KEYWORDS:

Asperger's disorder; autistic disorder; executive function deficits; repetitive transcranial magnetic stimulation; treatment

PMID:
28346865
PMCID:
PMC5510034
DOI:
10.1089/cap.2016.0146
[Indexed for MEDLINE]
Free PMC Article
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3.
Am Fam Physician. 2016 Dec 15;94(12):972-979.

Autism Spectrum Disorder: Primary Care Principles.

Author information

1
Naval Hospital Jacksonville, Jacksonville, FL, USA.
2
Naval Hospital Pensacola, Pensacola, FL, USA.

Abstract

Autism spectrum disorder is characterized by difficulty with social communication and restricted, repetitive patterns of behavior, interest, or activities. The Diagnostic and Statistical Manual of Mental Disorders, 5th ed., created an umbrella diagnosis that includes several previously separate conditions: autistic disorder, Asperger syndrome, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified. There is insufficient evidence to recommend screening for autism spectrum disorder in children 18 to 30 months of age in whom the disorder is not suspected; however, there is a growing body of evidence that early intensive behavioral intervention based on applied behavior analysis improves cognitive ability, language, and adaptive skills. Therefore, early identification of autism spectrum disorder is important, and experts recommend the use of a validated screening tool at 18- and 24-month well-child visits. Medications can be used as adjunctive treatment for maladaptive behaviors and comorbid psychiatric conditions, but there is no single medical therapy that is effective for all symptoms of autism spectrum disorder. Prognosis is heavily affected by the severity of diagnosis and the presence of intellectual disability. Children with optimal outcomes receive earlier, more intensive behavioral interventions and less pharmacologic treatment.

PMID:
28075089
[Indexed for MEDLINE]
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4.
JAMA Psychiatry. 2016 Sep 1;73(9):928-37. doi: 10.1001/jamapsychiatry.2016.1232.

Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial.

Author information

1
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada2Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
2
Nisonger Center, The Ohio State University, Columbus.
3
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
4
Department of Psychiatry, Vanderbilt University, Nashville, Tennessee.
5
Biostatistics Center, Massachusetts General Hospital, Boston.
6
Department of Psychology, Nationwide Children's Hospital, Columbus, Ohio8Department of Pediatrics and Psychology, The Ohio State University, Columbus.
7
Department of Pediatrics, Vanderbilt University, Nashville, Tennessee.
8
Department of Pediatrics, CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
9
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
10
Biostatistics Center, Massachusetts General Hospital, Boston11Department of Medicine, Harvard Medical School, Boston, Massachusetts.
11
Department of Psychiatry and Sackler Institute for Developmental Psychobiology, Columbia University, New York, New York13New York State Psychiatric Institute, New York14Center for Autism and the Developing Brain, New York Presbyterian Hospital, White Plains, New York.

Abstract

IMPORTANCE:

Atypical antipsychotic medications are indicated for the treatment of irritability and agitation symptoms in children with autism spectrum disorder (ASD). Unfortunately, these medications are associated with weight gain and metabolic complications that are especially troubling in children and with long-term use.

OBJECTIVE:

To evaluate the efficacy of metformin for weight gain associated with atypical antipsychotic medications in children and adolescents with ASD (defined in the protocol as DSM-IV diagnosis of autistic disorder, Asperger disorder, or pervasive developmental disorder not otherwise specified), aged 6 to 17 years.

DESIGN, SETTING, AND PARTICIPANTS:

A 16-week, double-blind, placebo-controlled, randomized clinical trial was conducted at 4 centers in Toronto, Ontario, Canada; Columbus, Ohio; Pittsburgh, Pennsylvania; and Nashville, Tennessee. In all, 209 potential participants were screened by telephone, 69 individuals provided consent, and 61 participants were randomized to receive metformin or placebo between April 26, 2013, and June 24, 2015.

INTERVENTIONS:

Metformin or matching placebo titrated up to 500 mg twice daily for children aged 6 to 9 years and 850 mg twice daily for those 10 to 17 years.

MAIN OUTCOMES AND MEASURES:

The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables. Safety, tolerability, and efficacy analyses all used a modified intent-to-treat sample comprising all participants who received at least 1 dose of medication.

RESULTS:

Of the 61 randomized participants, 60 participants initiated treatment (45 [75%] male; mean [SD] age, 12.8 [2.7] years). Metformin reduced BMI z scores from baseline to week 16 significantly more than placebo (difference in 16-week change scores vs placebo, -0.10 [95% CI, -0.16 to -0.04]; P = .003). Statistically significant improvements were also noted in secondary body composition measures (raw BMI, -0.95 [95% CI, -1.46 to -0.45] and raw weight, -2.73 [95% CI, -4.04 to -1.43]) but not in metabolic variables. Overall, metformin was well tolerated. Five participants in the metformin group discontinued treatment owing to adverse events (agitation, 4; sedation, 1). Participants receiving metformin vs placebo experienced gastrointestinal adverse events during a significantly higher percentage of treatment days (25.1% vs 6.8%; P = .005).

CONCLUSIONS AND RELEVANCE:

Metformin may be effective in decreasing weight gain associated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT01825798.

[Indexed for MEDLINE]
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5.
Clin Neuropharmacol. 2015 Sep-Oct;38(5):177-82. doi: 10.1097/WNF.0000000000000096.

Mood Stabilizers in Children and Adolescents With Autism Spectrum Disorders.

Author information

1
Division of Child and Adolescent Neuropsychiatry, University Hospital of Siena, Siena, Italy.

Abstract

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders including autistic disorder, Asperger syndrome, and pervasive developmental disorder not otherwise specified as to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. All these categories are grouped together in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, classification under the category of Autism Spectrum Disorders.Behavioral disorders including irritability, attention-deficit/hyperactivity disorder (ADHD) symptoms, and aggression are additional symptoms found in up to 20% of children and adolescents with ASD and require careful evaluation for appropriate treatment. Attention-deficit/hyperactivity disorder is defined by impaired attention, hyperactivity, and impulsivity, whereas ASD is defined by social dysfunction, communicative impairment, and restricted/repetitive behaviors. They should be distinctly evaluated in children and adolescents with ASD and intellectual disability in contrast to individuals without intellectual disability, because significant differences between these conditions exist. Mood disorders are also common in ASD and should be systematically investigated in this population of children and adolescents. Approximately 50% of children and adolescents with ASD receive medication for comorbid behavioral/ADHD and mood symptoms, mostly stimulants, antiepileptics and antipsychotics. Guidelines for the evaluation and treatment including medications for ADHD-like symptoms have recently been provided and should be carefully considered. Antiepileptic drugs are commonly used in ASDs with epilepsy, because seizures are associated with ASD in 10% to 30% of young patients, and as mood stabilizers. Lithium is another option for children and adolescents with ASD who present with symptoms of a mood disorder, such as elevated moods/euphoria, mania, and paranoia, whether accompanied or not by irritability. Experimental treatments are under investigation and currently include arbaclofen, a γ-aminobutyric acid agent, and N-acetylcisteine, a glutamate agent.

PMID:
26366961
DOI:
10.1097/WNF.0000000000000096
[Indexed for MEDLINE]
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6.

The canonical Wnt signaling pathway in autism.

Author information

1
Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Yixueyuan Road 138, Shanghai 200032, China. ruixilee@shmu.edu.cn.

Abstract

Mounting attention is being focused on the canonical Wnt signaling pathway which has been implicated in the pathogenesis of autism in some our and other recent studies. The canonical Wnt pathway is involved in cell proliferation, differentiation and migration, especially during nervous system development. Given its various functions, dysfunction of the canonical Wnt pathway may exert adverse effects on neurodevelopment and therefore leads to the pathogenesis of autism. Here, we review human and animal studies that implicate the canonical Wnt signal transduction pathway in the pathogenesis of autism. We also describe the crosstalk between the canonical Wnt pathway and the Notch signaling pathway in several types of autism spectrum disorders, including Asperger syndrome and Fragile X. Further research on the crosstalk between the canonical Wnt signaling pathway and other signaling cascades in autism may be an efficient avenue to understand the etiology of autism and ultimately lead to alternative medications for autism-like phenotypes.

PMID:
24365182
[Indexed for MEDLINE]
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7.
J Sep Sci. 2013 Sep;36(18):3042-9. doi: 10.1002/jssc.201300486. Epub 2013 Aug 12.

Development and optimization of the determination of pharmaceuticals in water samples by SPE and HPLC with diode-array detection.

Author information

1
Department of Analytical Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Zagreb, Croatia.

Abstract

This paper describes the development, optimization, and validation of a method for the determination of five pharmaceuticals from different therapeutic classes (antibiotics, anthelmintics, glucocorticoides) in water samples. Water samples were prepared using SPE and extracts were analyzed by HPLC with diode-array detection. The efficiency of 11 different SPE cartridges to extract the investigated compounds from water was tested in preliminary experiments. Then, the pH of the water sample, elution solvent, and sorbent mass were optimized. Except for optimization of the SPE procedure, selection of the optimal HPLC column with different stationary phases from different manufacturers has been performed. The developed method was validated using spring water samples spiked with appropriate concentrations of pharmaceuticals. Good linearity was obtained in the range of 2.4-200 μg/L, depending on the pharmaceutical with the correlation coefficients >0.9930 in all cases, except for ciprofloxacin (0.9866). Also, the method has revealed that low LODs (0.7-3.9 μg/L), good precision (intra- and interday) with RSD below 17% and recoveries above 98% for all pharmaceuticals. The method has been successfully applied to the analysis of production wastewater samples from the pharmaceutical industry.

KEYWORDS:

HPLC; Optimization; Pharmaceuticals; Production wastewater; SPE

PMID:
23857564
DOI:
10.1002/jssc.201300486
[Indexed for MEDLINE]
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8.
JAMA. 2013 Apr 24;309(16):1696-703. doi: 10.1001/jama.2013.2270.

Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism.

Author information

1
Department of Neurology, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark. jakob@farm.au.dk

Abstract

IMPORTANCE:

Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. However, prenatal exposure to valproate may increase the risk of autism.

OBJECTIVE:

To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring.

DESIGN, SETTING, AND PARTICIPANTS:

Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first.

MAIN OUTCOMES AND MEASURES:

Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy.

RESULTS:

Of 655,615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1.7-4.9]) and an absolute risk of 2.50% (95% CI, 1.30%-4.81%) for childhood autism (adjusted HR, 5.2 [95% CI, 2.7-10.0]). When restricting the cohort to the 6584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (95% CI, 2.20%-7.81%) (adjusted HR, 1.7 [95% CI, 0.9-3.2]), and the absolute risk of childhood autism was 2.95% (95% CI, 1.42%-6.11%) (adjusted HR, 2.9 [95% CI, 1.4-6.0]) vs 2.44% (95% CI, 1.88%-3.16%) for autism spectrum disorder and 1.02% (95% CI, 0.70%-1.49%) for childhood autism among 6152 children not exposed to valproate.

CONCLUSIONS AND RELEVANCE:

Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.

PMID:
23613074
PMCID:
PMC4511955
DOI:
10.1001/jama.2013.2270
[Indexed for MEDLINE]
Free PMC Article
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9.
BMC Psychiatry. 2012 Nov 29;12:215. doi: 10.1186/1471-244X-12-215.

Yokukansan (TJ-54) for treatment of pervasive developmental disorder not otherwise specified and Asperger's disorder: a 12-week prospective, open-label study.

Author information

1
Department of Psychiatry, Shimane University School of Medicine, 89-1 Enyacho, Izumo 693-8501, Japan. miyanyan@med.shimane-u.ac.j

Abstract

BACKGROUND:

Numerous medications have been tested on patients with pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger's disorder. Although many of these medications have been demonstrated to be useful, no clear primary treatment for PDD-NOS and Asperger's disorder has emerged. Despite the efficacy of some of the medicines, the acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Japanese herbal medicine yokukansan (TJ-54) may be safe and useful in treating behavioral and psychological symptoms in dementia and some neuropsychiatric disorders. We aimed at evaluating both the efficacy and safety of TJ-54 in patients with well-defined PDD-NOS and Asperger's disorder.

METHODS:

This was a 12-week prospective, open-label investigation of TJ-54 in 40 children, adolescents, and adults diagnosed with PDD-NOS or Asperger's disorder. Primary outcome measures included the Clinical Global Impressions-Severity of Illness Scale (CGI-S) and the Aberrant Behavior Checklist-Iritability subscale score (ABC-I).

RESULTS:

Forty subjects, ages 8-40 years (mean 22.7 ± 7.3 years) received a mean final TJ-54 dosage of 6.4 ± 1.3 g/day (range 2.5-7.5 g/day). Full-scale intelligence quotient (IQ) scores ranged from 70 to 110 (mean 88.9 ± 13.2). Thirty-six (90%) of 40 subjects showed fewer interfering symptoms of irritability, including aggression, self-injury, and tantrums, with a final CGI-S of 1 or 2 (normal, not at all ill or borderline mentally ill) and a 80% or greater improvement on the ABC-I. The mean CGI-S score at baseline was 6.8 ± 0.8 whereas scores at end point was 1.9 ± 0.1 (< 0.0001). ABC-I scores ranged from 11 to 29 (mean 17.4 ± 3.66) at baseline, whereas scores at week 12 ranged from 0 to 5 (mean 0.93 ± 0.97) (p <0.0001). TJ-54 was well tolerated. No subject exited the study due to a drug-related adverse event.

CONCLUSIONS:

These preliminary data suggest that TJ-54 may be effective and well tolerated for treatment of severe irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech in patients with PDD-NOS or Asperger's disorder. However, given the characteristics of this trial, the present findings should be taken cautiously, and larger-scale placebo-controlled studies are needed to elucidate the efficacy and tolerability of TJ-54 in this understudied population.

PMID:
23194148
PMCID:
PMC3533891
DOI:
10.1186/1471-244X-12-215
[Indexed for MEDLINE]
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10.
J Child Adolesc Psychopharmacol. 2012 Aug;22(4):277-83. doi: 10.1089/cap.2011.0129. Epub 2012 Jul 31.

The effects of aripiprazole on electrocardiography in children with pervasive developmental disorders.

Author information

1
Section of Pediatric Cardiology, Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana 46202-5200, USA.

Abstract

OBJECTIVES:

Psychotropic medications, including the atypical antipsychotics, have historically been scrutinized for cardiac effects and risk of sudden death. Aripiprazole is an atypical antipsychotic approved for pediatric use in schizophrenia, bipolar I disorder, and autistic disorder. Adult studies have evaluated aripiprazole's effects on electrocardiograms, but no pediatric studies have been published to date.

METHODS:

Electrocardiographic data were collected from children and adolescents participating in a 14-week, prospective, open-label study (n=25) of aripiprazole for irritability in pervasive developmental disorder not otherwise specified and Asperger's disorder. A 12-lead electrocardiogram was obtained at the baseline and end point visits. The electrocardiograms were evaluated for abnormal findings, and the PR, QRS, QT(c), and RR intervals were recorded. The QT interval was corrected using Bazett's, United States Food and Drug Administration (FDA) Pharmacology Division, and Fridericia's formulas.

RESULTS:

Twenty-four subjects received both baseline and posttreatment electrocardiograms. The mean age was 8.6 years (range 5-17 years). The average final aripiprazole dose was 7.8 mg/day (range 2.5-15 mg/day). There were no significant differences noted with the PR, QRS, RR, and QT(c) intervals after aripiprazole therapy. Also, there was no significant correlation between the dose given and the percent change in the QT(c). No post-treatment QT(c) exceeded 440 ms.

CONCLUSIONS:

To our knowledge, this is the first systematic evaluation of the cardiac effects of aripiprazole in children and adolescents. The results are consistent with previously published literature in adults that aripiprazole has no significant cardiac effects and can be deemed a low risk for causing sudden death. It will be important to confirm these findings in a randomized controlled trial.

PMID:
22849533
PMCID:
PMC3472675
DOI:
10.1089/cap.2011.0129
[Indexed for MEDLINE]
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11.
Am J Intellect Dev Disabil. 2012 May;117(3):233-42. doi: 10.1352/1944-7558-117.3.233.

Vaccine-related beliefs and practices of parents of children with autism spectrum disorders.

Author information

1
UCLA Fielding School of Public Health, Department of Health Services, Los Angeles, CA 90095-1772, USA. abazzano@ucla.edu

Abstract

Although the assertion of a link between vaccines and autism has been scientifically rejected, the theory continues to be popular and may influence the attitudes of parents of children with autism spectrum disorders. The authors sought to assess how often parents change or discontinue their child's vaccine schedule after autism spectrum disorder diagnosis and whether beliefs about the etiology of autism affect their decision to do so. The authors surveyed 197 (43%) of 460 eligible parents of children under 18 years of age with autism spectrum disorders who were enrolled in a state-funded agency that provides services to those with developmental disabilities in western Los Angeles County. Half of the parents discontinued or changed vaccination practices, and this was associated with a belief that vaccines contributed to autism spectrum disorders, indicating a potential subset of undervaccinated children. Educational tools should be designed to assist physicians when talking to parents of children with autism spectrum disorders about vaccination.

PMID:
22716265
DOI:
10.1352/1944-7558-117.3.233
[Indexed for MEDLINE]
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12.
Psychiatriki. 2012 Jun;23 Suppl 1:66-73.

[The projection of autism spectrum disorders in adult life].

[Article in Greek, Modern]

Author information

1
2nd Department of Psychiatry, National and Kapodistrian University of Athens, "Attikon" University General Hospital of Athens, Athens, Greece.

Abstract

Autism Spectrum Disorders (ASDs) consist a group of neurodevelopmental disorders that are usually diagnosed in early childhood but they persist throughout life, although significant changes can happen. The prevalence of the ASDs is estimated to be 1-1.2%. Subjects with the more severe form of the disorder that are usually characterised by the absence of a communicative language and learning difficulties of various severity, are often referred as persons with lower functioning. In the other end of the spectrum we can find subjects with less severe symptomatology, communicative language and at least of normal intelligence that are referred as high functioning autistic people or -in case of an absence of a language delay- as suffering from Asperger syndrome. The lower functioning adults can be referred to an adult psychiatrist mainly due to their behavioral problems and disruptive behaviors. Their inability to express their difficulties, due to their language restrictions and empathy deficits, can lead these people to behavioural deviances (often self- or hetero-destructive) that challenge their personal environment ending up in the pursuit of psychiatric help. In most cases, although not always justified, psychotropic medications will be prescribed in an attempt to control their maladaptive behaviors. Special attention should be paid to the catatonic exacerbation of ASD, which can be exhibited after adolescence. The catatonic features presented shouldn't be perceived as a possible comorbidity with another disorder, such as schizophrenia, but rather as an extreme form anxiety within the context of an ASD. High Functioning adults with ASDs are more difficult to be detected, but they may also need psychiatric consultation. These subjects may have never been diagnosed with an ASD, but they could have in their history a variety of diagnostic categorizations. Their accurate diagnosis could be further hampered in cases where they are exhibiting remarkable abilities, professional success or even an adequate social adaptation, such as marriage and family. Very often their symptoms will be confused with those of other disorders and they will be also prescribed psychotropic medication with very few, if any, results. In the current paper, we will point out the symptoms and situations that should alert the psychiatrist for the presence of an ASD in an adult with a normal intelligence and adequate functioning that is referred to him for bizarre ideas or behaviors. The designated diagnostic procedure for the ascertainment of the ASD in this case is similar to the one followed for children and adolescents and comprises of a detailed developmental history and a relevant observation and interview. Finally, we will discuss the most common difficulties in the differential diagnosis of the high functioning adults with an ASD from those suffering from Obsessive Compulsive Disorder, Schizoid Personality Disorder, Schizophrenia and Psychosis, and we will provide key issues that can be of an assistance in the more accurate assessment and categorization of the presented symptoms.

PMID:
22796975
[Indexed for MEDLINE]
13.
Expert Opin Pharmacother. 2012 Aug;13(11):1615-29. doi: 10.1517/14656566.2012.674110. Epub 2012 May 3.

Pharmacotherapy to control behavioral symptoms in children with autism.

Author information

1
Indiana University School of Medicine and Christian Sarkine Autism Treatment Center, Riley Hospital for Children, Department of Psychiatry, IN, USA.

Abstract

INTRODUCTION:

Autistic disorder, Asperger's disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS) are pervasive developmental disorders (PDDs) frequently associated with behavioral symptoms that may require pharmacotherapy to manage.

AREAS COVERED:

Behavioral symptoms in children with autism include interfering repetitive behaviors, irritability, and hyperactivity and inattention, among others. The psychotropic medications examined in this review include: serotonin reuptake inhibitors, typical and atypical antipsychotics, medications used to treat attention-deficit/hyperactivity disorder, naltrexone, buspirone, divalproex sodium, lamotrigine, levetiracetam, memantine, mirtazapine, riluzole, pioglitazone, and topiramate.

EXPERT OPINION:

For the treatment of interfering repetitive behaviors, serotonin reuptake inhibitors demonstrate less efficacy and are more poorly tolerated in children with autism compared to adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in children with autism and other PDDs. For the treatment of hyperactivity and inattention, psychostimulants demonstrate some benefit. However, they are overall less efficacious and cause more side effects in children with PDDs compared to typically developing children with attention-deficit/hyperactivity disorder. Results from double-blind, placebo-controlled trials of these agents and others for the treatment of the behavioral symptom domains described above will be discussed in this review.

PMID:
22550944
DOI:
10.1517/14656566.2012.674110
[Indexed for MEDLINE]
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14.
Environ Sci Pollut Res Int. 2012 May;19(4):1033-42. doi: 10.1007/s11356-012-0782-7. Epub 2012 Apr 29.

RO/NF membrane treatment of veterinary pharmaceutical wastewater: comparison of results obtained on a laboratory and a pilot scale.

Author information

1
Department of Physical Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10000 Zagreb, Croatia. dolar@fkit.hr

Abstract

BACKGROUND:

Emerging contaminants (ECs) are commonly derived from industrial wastewater, which is often a consequence of an inadequate treatment of the latter. Improperly pretreated pharmaceutical wastewater could cause difficulties in operations of wastewater treatment plants while incomplete elimination of ECs during the processing might result in their appearance in drinking water.

METHODS:

This paper deals with membrane treatment of pharmaceutical wastewater on a laboratory and a pilot scale as well as with the removal of the following veterinary pharmaceuticals (VPs) (sulfamethoxazole, trimethoprim, ciprofloxacin, dexamethasone, and febantel).

RESULTS:

The pretreatment of pharmaceutical wastewater by means of coagulation and microfiltration (MF) prevented the irreversible fouling of the fine porous structure of the reverse osmosis (RO) and nanofiltration (NF) membranes which were used in the final stage of wastewater processing. The percentage of the removal of the selected VPs ranges from 94% to almost 100% in the case of NF and RO membranes in both scales. The recovery percentage concerning the pilot scale amounted to 88%. Membrane cleaning was successfully carried out in both scales.

CONCLUSIONS:

The differences in retention between laboratory and pilot tests are due to different raw wastewater quality and different recovery and hydrodynamic of the two systems. Fouling and concentration polarization were more pronounced in laboratory setup (frame-plate module) than in pilot unit (spiral module). The proposed integrated membrane treatment (coagulation, MF, NF, and RO) can be employed for treatment of wastewater originating from pharmaceutical factory. The obtained permeate can be safely discharged to sewer system or could be reused in manufacturing process.

PMID:
22544555
DOI:
10.1007/s11356-012-0782-7
[Indexed for MEDLINE]
Icon for Springer
15.
Water Sci Technol. 2012;65(2):317-23. doi: 10.2166/wst.2012.855.

Efficiency of RO/NF membranes at the removal of veterinary antibiotics.

Author information

1
Faculty of Chemical Engineering and Technology, Department of Physical chemistry, Zagreb, Croatia. dolar@fkit.hr

Abstract

The production of pharmaceuticals has increased rapidly during the last several decades as they have been used for the health of both humans and animals. Routes of environmental exposure include the release of treated wastewater, the land disposal of livestock manures and municipal biosolids (i.e. sewage sludge), as well as the use of medicated aquaculture feed. This study deals with application of reverse osmosis (RO) and nanofiltration (NF) membranes for removing of antibiotic residues (sulfamethoxazole, trimethoprim, ciprofloxacin, dexamethasone and febantel) and their mixture. According to the results obtained in this work the use of RO (LFC-1 and XLE) and the tight NF (NF90) membranes are recommended to achieve a high level of retention (>95%) of all selected veterinary antibiotics (VAs). Nanofiltration NF270, NF and HL membranes showed a lower rejection of individual components, but much higher in a mixture solution, due to the synergistic effect.

PMID:
22233911
DOI:
10.2166/wst.2012.855
[Indexed for MEDLINE]
16.
Ann Epidemiol. 2012 Jan;22(1):1-8. doi: 10.1016/j.annepidem.2011.10.007.

High prescription drug use and associated costs among Medicaid-eligible children with autism spectrum disorders identified by a population-based surveillance network.

Author information

1
Department of Medicine, Division of Biostatistics and Epidemiology, Medical University of South Carolina, Charleston, USA. logans@musc.edu

Abstract

PURPOSE:

We assessed medication use and associated costs among 8- and 15-year-old children with autism spectrum disorders (ASD) identified by the South Carolina Autism and Developmental Disabilities Monitoring (SCADDM) Network.

METHODS:

All Medicaid-eligible SCADDM-identified children with ASD from surveillance years 2006 and 2007 were included (n = 263). Children were classified as ASD cases when documented behaviors consistent with the DSM-IV-TR criteria for autistic disorder, Asperger disorder, or pervasive developmental disorder-not otherwise specified were present in health and education evaluation records. Medication and cost data were obtained by linking population-based and Medicaid data.

RESULTS:

All 263 SCADDM-identified children had Medicaid data available; 56% (n = 147) had a prescription of any type, 40% (n = 105) used psychotropic medication, and 20% (n = 52) used multiple psychotropic classes during the study period. Common combinations were (1) attention deficit hyperactivity disorder medications and an antihypertensive, antidepressant or antipsychotic; and (2) antidepressants and an antipsychotic. Multiple psychotropic classes were more common among older children. Both the overall distribution of the number of prescription claims and medication costs varied significantly by age.

CONCLUSIONS:

Results confirm that medication use in ASD, alone or in combination, is common, costly, and may increase with age.

PMID:
22153288
PMCID:
PMC3240812
DOI:
10.1016/j.annepidem.2011.10.007
[Indexed for MEDLINE]
Free PMC Article
Icon for Elsevier Science Icon for PubMed Central
17.
J Environ Sci (China). 2011;23(8):1299-307.

Effect of water matrices on removal of veterinary pharmaceuticals by nanofiltration and reverse osmosis membranes.

Author information

1
Department of Physical Chemistry, Faculty of Chemical Engineering and Technology, Marulidev trg 19, 10000 Zagreb, Croatia. dolar@fkit.hr

Abstract

This study explored the removal of five veterinary pharmaceuticals (VPs) (sulfamethoxazole (SMETOX), trimethoprim (TMP), ciprofloxacin (CIPRO), dexamethasone (DEXA) and febantel (FEBA)) from different water matrices (Milli-Q water, model water, tap water and real pharmaceutical wastewater using four types of nanofiltration (NF) membranes (NF90, NF270, NF and HL) and two reverse osmosis (RO) membranes (LFC-1 and XLE). All VPs were added to different water matrices at a concentration of 10 mg/L. Rejections of VPs and water flux were measured. The rejection increased with increase of molecular weight. The highest rejections were obtained with RO membranes (LFC-1, XLE) and tight NF (NF90) membrane. In general, the rejection of VPs was higher in model water and tap water than in Milli-Q water, but the water flux was lower. This was mainly explained by ion adsorption inside the membranes pores. Narrower pore size counteracted the effect of presence of low concentration of natural organic matter (NOM) in tap water. The NOM was assumed to enhance the adsorption of VPs onto membrane surface, increased the size exclusion and electrostatic repulsion also appeared during the transport. Investigated water matrices had influence on water flux decline due to their complexity.

PMID:
22128537
[Indexed for MEDLINE]
18.
Autism Res. 2011 Apr;4(2):98-108. doi: 10.1002/aur.176. Epub 2011 Feb 28.

Behavioral and cardiac responses to emotional stroop in adults with autism spectrum disorders: influence of medication.

Author information

1
Department of Psychology, Neuroscience & Behavior, McMaster University, Hamilton, Ontario, Canada. mathewkj@mcmaster.ca

Abstract

Researchers have recently hypothesized that autism spectrum disorders (ASD) may be partly characterized by physiological over-arousal. One way to assess physiological arousal is through autonomic measures. Here heart period (HP) and parasympathetic activity measured by respiratory sinus arrhythmia (RSA) were examined in adults with ASD and matched controls at rest and during performance of an emotional Stroop task. Resting HP and RSA were lower in adults with ASD than in matched controls, consistent with hypothesized over-arousal in ASD. However, dividing the ASD group on the basis of antipsychotic medication usage revealed that group differences in autonomic arousal may be related to the effects of these medications or their correlates. Autonomic adjustments for Stroop performance were comparable across groups, but in the control group, larger RSA reductions were correlated with faster responding (i.e., better performance). This relation was reversed in the unmedicated ASD group and absent in the medicated ASD group. Findings highlight the importance of considering medication status in the recently burgeoning area of psychophysiological studies of autism.

PMID:
21360828
DOI:
10.1002/aur.176
[Indexed for MEDLINE]
Icon for Wiley
19.
Am J Med Genet B Neuropsychiatr Genet. 2011 Jun;156B(4):413-20. doi: 10.1002/ajmg.b.31176. Epub 2011 Feb 25.

PARK2 copy number aberrations in two children presenting with autism spectrum disorder: further support of an association and possible evidence for a new microdeletion/microduplication syndrome.

Author information

1
Tesserae Genetics, Dallas, Texas, USA. ascheuerle@swbell.net

Abstract

Microdeletions of PARK2 have been reported previously in seven patients with autism spectrum disorder. There are no reports of PARK2 microduplications in this population. Presented are two patients, one with deletion and the other with duplication, both with autism spectrum disorder, though their syndromic phenotypes vary. The deletion patient is cognitively normal and ectomorphic: the duplication patient is cognitively impaired, underweight and short. Further, the microduplication patient has demonstrated adverse medication reactions to psychotropic medications active in the dopamine metabolic pathway: cyclopentolate, lisdexamfetamine, methylphenidate. These patients support an association between PARK2 mutations and autism spectrum disorder and suggest that duplications may be equally causative. It is hypothesized that the disparate patient phenotypes may represent a deletion/duplication syndrome and that the adverse medication reactions may be a pharmacogenetic phenomenon.

PMID:
21360662
DOI:
10.1002/ajmg.b.31176
[Indexed for MEDLINE]
Icon for Wiley
20.
Anal Bioanal Chem. 2010 Oct;398(3):1185-94. doi: 10.1007/s00216-010-4004-1. Epub 2010 Jul 29.

Determination of multi-class pharmaceuticals in wastewater by liquid chromatography-tandem mass spectrometry (LC-MS-MS).

Author information

1
Department of Analytical Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, 10000, Zagreb, Croatia. sandra.babic@fkit.hr

Abstract

An analytical method for multi-class pharmaceuticals determination in wastewater has been developed and validated. Target compounds were: sulfonamides (sulfadiazine, sulfaguanidine, sulfamethazine, sulfamethoxazole), fluoroquinolones (ciprofloxacin, enrofloxacin, norfloxacin), diaminopyrimidine (trimethoprim), anaesthetic (procaine), anthelmintic (praziquantel and febantel), and macrolide (roxithromycin). The method involves pre-concentration and clean-up by solid-phase extraction (SPE) using Strata-X extraction cartridges at pH 4.0. Target analytes were identified and quantitatively determined by liquid chromatography-tandem mass spectrometry using multiple reaction monitoring (MRM). Recoveries were higher than 50% with relative standard deviation (RSD) below 18.3% for three concentrations. Only for sulfaguanidine was low recovery obtained. Matrix effect was evaluated using matrix-matched standards. The method detection limit (MDL) was between 0.5 and 5 ng L(-1) in spiked water samples. The precision of the method, calculated as relative standard deviation, ranged from 0.5 to 2.0% and from 1.4 to 8.3 for intra-day and inter-day analysis, respectively. The described analytical method was used for determination of pharmaceuticals in effluent wastewaters from the pharmaceutical industry.

PMID:
20669010
DOI:
10.1007/s00216-010-4004-1
[Indexed for MEDLINE]
Icon for Springer
21.
Clin Neuropharmacol. 2010 May;33(3):114-20. doi: 10.1097/WNF.0b013e3181d6f7ad.

Cholinergic abnormalities in autism: is there a rationale for selective nicotinic agonist interventions?

Author information

1
Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA 23507-1912, USA. deutscsi@evms.edu

Abstract

The core dysfunctions of autism spectrum disorders, which include autistic disorder, Asperger disorder, and pervasive developmental disorder not otherwise specified, include deficits in socialization and communication and a need for the preservation of "sameness;" intellectual impairment and epilepsy are common comorbidities. Data suggest that pathological involvement of cholinergic nuclei and altered expression of acetylcholine receptors, particularly nicotinic acetylcholine receptors, occur in brain of persons with autistic disorder. However, many of these studies involved postmortem tissue from small samples of primarily adult persons. Thus, the findings may reflect compensatory changes and may relate more closely to intellectual impairment and the confounding effects of seizures and medications, as opposed to the core dysfunctions of autism. Nonetheless, because of the roles played by acetylcholine receptors in general, and nicotinic acetylcholine receptors in particular, in normal processes of attention, cognition, and memory, selective cholinergic interventions should be explored for possible therapeutic effects. Additionally, there are electrophysiological data that complement the clinical observations of frequent comorbid seizure disorders in these patients, suggesting a disturbance in the balance of excitatory and inhibitory tone in the brains of persons with autistic disorders. Conceivably, because the alpha7 nicotinic acetylcholine receptor is located on the surface of gamma-aminobutyric acid inhibitory neurons, selective stimulation of this receptor would promote gamma-aminobutyric acid's release and restore diminished inhibitory tone. The development of agonists and partial agonists for nicotinic acetylcholine receptors and positive allosteric modulators that enhance the efficiency of coupling between the binding of agonist and channel opening should facilitate consideration of clinical trials.

PMID:
20190638
DOI:
10.1097/WNF.0b013e3181d6f7ad
[Indexed for MEDLINE]
Icon for Wolters Kluwer
22.
J Sep Sci. 2010 Feb;33(2):258-67. doi: 10.1002/jssc.200900571.

Development and optimization of the SPE procedure for determination of pharmaceuticals in water samples by HPLC-diode array detection.

Author information

1
Department of Analytical Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Zagreb, Croatia. dmutavdz@fkit.hr

Abstract

This paper focuses on the investigation of different types of SPE sorbents for the preconcentration of eight veterinary pharmaceuticals from water samples. The pharmaceuticals studied were sulfamethazine, sulfadiazine, sulfaguanidine, trimethoprim, oxytetracycline, enrofloxacin, norfloxacin and penicillin G/procaine. Five different SPE materials (Strata-X, Strata-X-C, Strata SDB-L, Strata C8 and Strata C18) from Phenomenex were compared with Oasis HLB with a view to obtaining the best cartridges for all pharmaceuticals investigated. Extraction efficiency was determined by HPLC with diode array detection (DAD). HPLC-DAD separation and quantification of the selected pharmaceuticals were carried out under gradient elution by a binary mixture of 0.01 M oxalic acid and ACN based on cyano modified column (LiChrosphere 100 CN) from Merck. Strata-X provided the best results in the preconcentration of 100 mL water samples, yielding average pharmaceutical recoveries of higher than 90%, except for sulfaguanidine (76.1%). The developed Strata-X-HLPC-DAD method was validated and applied, for the efficient investigation of reverse osmosis/nanofiltration membranes and for the removal of these eight pharmaceuticals from the production wastewater samples. NF90 and XLE membranes were shown to be the best for the rejection of all investigated pharmaceuticals.

PMID:
20041448
DOI:
10.1002/jssc.200900571
[Indexed for MEDLINE]
Icon for Wiley
23.
Int J Paediatr Dent. 2009 Nov;19(6):390-8. doi: 10.1111/j.1365-263X.2009.01011.x. Epub 2009 Jul 9.

Behaviour guidance in dental treatment of patients with autism spectrum disorder.

Author information

1
Department of Pediatric Dentistry, Tufts University School of Dental Medicine, Boston, MA 02111, USA. c.loo@tufts.edu

Abstract

BACKGROUND:

Autism spectrum disorder (ASD) is a neurodevelopmental disorder categorized into autism, pervasive developmental disorder - not otherwise specified (PDD-NOS) and Asperger syndrome.

AIMS:

To identify factors associated with the behaviour of patients with ASD in a dental setting, use of general anaesthesia (GA), and protective stabilization.

DESIGN:

The dental charts of 395 patients with ASD patients and 386 unaffected patients were reviewed. The following data were analysed: ASD diagnosis, age, gender, residence, seizure disorder, additional diagnosis (mental retardation, cerebral palsy, self-injurious behaviour or pica), medications, caries prevalence and severity, dental treatment history, behaviour, and behaviour guidance technique(s) used.

RESULTS:

Within both groups, younger patients were more uncooperative. ASD patients with autism were more uncooperative than patients with PDD-NOS; patients with an additional diagnosis were also more uncooperative. ASD patients with higher caries severity, who were uncooperative or female, were more likely to require GA. Use of protective stabilization was associated with lower caries severity, presence of seizure disorder, uncooperative behaviour, male gender, or residency in a group home/institution.

CONCLUSIONS:

Autism spectrum disorder patients with autism, younger age and an additional diagnosis were more uncooperative. Factors associated with the use of GA and protective stabilization in patients with ASD were also identified.

[Indexed for MEDLINE]
Icon for Wiley
24.
J Autism Dev Disord. 2009 Sep;39(9):1339-49. doi: 10.1007/s10803-009-0750-3. Epub 2009 May 12.

A longitudinal investigation of psychotropic and non-psychotropic medication use among adolescents and adults with autism spectrum disorders.

Author information

1
Waisman Center, University of Wisconsin-Madison, rm 561, Madison, WI 53705, USA. esbensen@waisman.wisc.edu

Abstract

Medication use was examined in 286 adolescents and adults with ASD over a 4.5 year period. A total of 70% were taking a psychotropic or non-psychotropic medication at the beginning of the study. Both the number of psychotropic and non-psychotropic medications taken, and the proportion of individuals taking these medications, increased significantly over the study period, with 81% taking at least one medication 4.5 years later. Our findings suggested a high likelihood of staying medicated over time. Thus, adolescents and adults with ASD are a highly and increasingly medicated population.

PMID:
19434487
PMCID:
PMC2829244
DOI:
10.1007/s10803-009-0750-3
[Indexed for MEDLINE]
Free PMC Article
Icon for Springer Icon for PubMed Central

Publication types, MeSH terms, Substance, Grant support

Publication types

MeSH terms

Substance

Grant support

26.
J Intellect Disabil Res. 2009 Feb;53(2):115-24. doi: 10.1111/j.1365-2788.2008.01134.x. Epub 2008 Nov 27.

Regression of language and non-language skills in pervasive developmental disorders.

Author information

1
Université de Montréal, Rivière-des-Prairies Hospital, Montreal, QC, Canada.

Abstract

BACKGROUND:

As part of the pervasive developmental disorders (PDD), there is a subgroup of individuals reported to have a different onset of symptom appearance consisting of an apparently normal early development, followed by a loss of verbal and/or non-verbal skills prior to 2 years of age. This study aims at comparing the symptomatology of children who displayed a regression and often an associated intellectual disability through investigation of two types of loss, namely language and other skill regression.

METHODS:

This study examined the occurrence of regression in 135 children with PDD, mean age 6.3 years. The sample was composed of 80 (59.4%) children diagnosed with autism, 44 (32.6%) with pervasive developmental disorder-not otherwise specified (PDD-NOS) and 11 (8%) with Asperger syndrome. The Autism Diagnostic Interview Revised (ADI-R) was used to evaluate the type of loss and to characterise associated factors including birth rank, gender and thimerosal exposure through vaccination.

RESULTS:

A total of 30 (22%) subjects regressed: nine (30%) underwent language regression alone, 17 (57%) lost a skill other than language and four (13%) lost both language and another skill. Significantly higher levels of regression were found in autism (30%) compared with PDD-NOS (14%) and Asperger syndrome (0%). Children who regressed in language skills spoke at a significantly earlier age ( = 12 months) than those who did not regress in this domain ( = 26 months). Parents and interviewers consistently reported developmental abnormalities prior to the loss. ADI-R domain mean scores indicated a more severe autistic symptomatology profile in children who regressed compared with those who did not, especially in the repetitive behaviour domain. Regression was not associated to thimerosal exposure, indirectly estimated by year of birth.

CONCLUSIONS:

A loss of skill, present in one out of five children with PDD, is associated with a slightly more severe symptomatology as measured by the ADI-R, particularly in the repetitive behaviours domain. Furthermore, although abnormalities are often noticed by the caregivers at the time of regression, the ADI-R reveals that other atypical behaviours were in fact present prior to the onset of regression in most cases. None of the secondary factors investigated were associated with regression. In children unexposed to thimerosal-containing vaccines, the rate of regression was similar to that reported in studies of samples exposed to thimerosal, suggesting that thimerosal has no specific association with regressive autism.

[Indexed for MEDLINE]
Icon for Wiley
27.
J Am Dent Assoc. 2008 Nov;139(11):1518-24.

The caries experience and behavior of dental patients with autism spectrum disorder.

Author information

1
Department of Pediatric Dentistry, School of Dental Medicine, Tufts University, Boston, MA 02111, USA. c.loo@tufts.edu

Abstract

BACKGROUND:

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. The authors conducted a study to evaluate the demographics, caries experience and behavior of patients with ASD and compare these characteristics with those of patients without ASD (unaffected patients).

METHODS:

The authors reviewed patients' charts and identified a group of 395 patients with ASD and a group of 386 unaffected patients. They obtained the following patient data for analysis: primary diagnosis, age, sex, residence (home versus institution or group home), presence of seizure disorder, additional diagnosis (mental retardation, cerebral palsy, self-injurious behavior or pica), medications, caries prevalence, caries severity and behavior.

RESULTS:

The ASD group had a male:female ratio of 4:1, and patients had a diagnosis of autism, pervasive developmental disorder-not otherwise specified or Asperger syndrome. Sex distribution was equal in the unaffected group, which was younger and had a higher decayed, missing and filled teeth (DMFT) score than did the ASD group. When the authors controlled for age and sex, they noted a statistically significant association between ASD and dental caries prevalence. A significantly higher percentage of patients with ASD than unaffected patients were uncooperative and required dental treatment to take place under general anesthesia. Caries prevalence and severity in patients with ASD were not associated with institutionalization, presence of seizure disorder or additional diagnosis.

CONCLUSIONS:

People with ASD were more likely to be caries-free and had lower DMFT scores than did their unaffected peers. Significantly more patients with ASD than unaffected patients were uncooperative and required general anesthesia to undergo dental treatment.

PMID:
18978390
[Indexed for MEDLINE]
Icon for Elsevier Science
28.
Neurocase. 2008;14(4):378-83. doi: 10.1080/13554790802368661.

Effect of propranolol on verbal problem solving in autism spectrum disorder.

Author information

1
Department of Radiology, Thompson Center, University of Missouri, Columbia, MO 65211, USA. beversdorfd@helath.missouri.edu

Abstract

The noradrenergic system modulates performance on tasks dependent on semantic and associative network flexibility (NF) in individuals without neurodevelopmental diagnoses in experiments using a beta-adrenergic antagonist, propranolol. Some studies suggest drugs decreasing noradrenergic activity are beneficial in ASD. In individuals without neurodevelopmental diagnoses, propranolol is beneficial only for difficult NF-dependent problems. However, in populations with altered noradrenergic regulation, propranolol also benefits performance for simple problems. Due to decreased flexibility of access to networks in ASD, we wished to examine the effect of propranolol on NF in ASD. ASD subjects benefited from propranolol on simple anagrams, whereas control subjects were impaired by propranolol. Further study will be necessary to confirm this finding in a larger sample and to compare clinical response with cognitive response to propranolol.

PMID:
18766980
DOI:
10.1080/13554790802368661
[Indexed for MEDLINE]
29.
Pediatrics. 2008 Mar;121(3):e441-8. doi: 10.1542/peds.2007-0984.

Psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders.

Author information

1
University of Pennsylvania School of Medicine, Department of Psychiatry, Philadelphia, PA 19104, USA. mandelld@mail.med.upenn.edu

Abstract

OBJECTIVE:

The objective of this study was to provide national estimates of psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders and to examine child and health system characteristics associated with psychotropic medication use.

METHODS:

This cross-sectional study used Medicaid claims for calendar year 2001 from all 50 states and Washington, DC, to examine 60,641 children with an autism spectrum disorder diagnosis. Logistic regression with random effects was used to examine the child, county, and state factors associated with psychotropic medication use.

RESULTS:

Of the sample, 56% used at least 1 psychotropic medication, 20% of whom were prescribed > or = 3 medications concurrently. Use was common even in children aged 0 to 2 years (18%) and 3 to 5 years (32%). Neuroleptic drugs were the most common psychotropic class (31%), followed by antidepressants (25%) and stimulants (22%). In adjusted analyses, male, older, and white children; those who were in foster care or in the Medicaid disability category; those who received additional psychiatric diagnoses; and those who used more autism spectrum disorder services were more likely to have used psychotropic drugs. Children who had a diagnosis of autistic disorder or who lived in counties with a lower percentage of white residents or greater urban density were less likely to use such medications.

CONCLUSIONS:

Psychotropic medication use is common among even very young children with autism spectrum disorders. Factors unrelated to clinical presentation seem highly associated with prescribing practices. Given the limited evidence base, there is an urgent need to assess the risks, benefits, and costs of medication use and understand the local and national policies that affect medication use.

Comment in

PMID:
18310165
PMCID:
PMC2861431
DOI:
10.1542/peds.2007-0984
[Indexed for MEDLINE]
Free PMC Article
Icon for HighWire Icon for PubMed Central
30.
Am J Ment Retard. 2007 Nov;112(6):401-17.

Transition and change in adolescents and young adults with autism: longitudinal effects on maternal well-being.

Author information

1
Waisman Center, University of Wisconsin-Madison 53705, USA. Lounds@Waisman.wisc.edu

Abstract

We investigated how change in the characteristics of 140 adolescents and young adults with an autism spectrum disorder (ASD) would predict subsequent change in maternal well-being and in the quality of the mother-child relationship. Overall patterns of improvement in maternal well-being and mother-child relationship quality were observed during the study. When the son or daughter had declining behavior problems, were prescribed more psychotropic medications, and exited from high school during the study period, mothers' well-being and perception of relationship quality improved to a greater extent. In addition, improvements in maternal well-being and relationship quality were observed in mothers of daughters, in mothers of individuals with mental retardation as well as ASD, and in mothers of those in better health.

[Indexed for MEDLINE]
Icon for Allen Press, Inc.
31.
Child Psychiatry Hum Dev. 2007 Apr;37(4):337-46.

Parent-assisted friendship training for children with autism spectrum disorders: effects of psychotropic medication.

Author information

1
UCLA School of Medicine, 300 UCLA Medical Plaza, Suite 1402, Los Angeles, CA, 90095-6967, USA, ffrankel@mednet.ucla.edu

Abstract

Twenty-five 6 to 13-year-old children with autism spectrum disorders, who were high functioning, were given 12 weeks of parent-assisted children's friendship training. Thirteen were prescribed various psychotropic medications by physicians in the community prior to treatment (medicated) while 12 were not (unmedicated). Two parent-rated and three teacher-rated social measures served as outcome variables. Results revealed that unmedicated subjects had greater positive change on three of these five measures when compared to children in the medicated group. It was hypothesized that being prescribed psychotropic medication was a marker for refractory psychosocial treatment response by children with autism spectrum disorders.

PMID:
17406973
DOI:
10.1007/s10578-007-0053-x
[Indexed for MEDLINE]
Icon for Springer
32.
Nihon Rinsho. 2007 Mar;65(3):522-6.

[Pharmacologic treatment of Asperger syndrome].

[Article in Japanese]

Author information

1
Tokyo Metropolitan Umegaoka Hospital.

Abstract

Asperger syndrome is associated with various dysfunctional and problematic behaviors, in addition to the core features of communication and social skills dysfunction that define these conditions. Although there is currently no pharmacologic cure for the core features of Asperger syndrome. This article discusses the various medications for the behavioral symptoms of Asperger syndrome, which include hyperactivity, aggression, tantrums, self-injury, depression, obsession and so on. Methylphenidate, SSRIs, atypical antipsychotics and mood stabilizer were introduced.

PMID:
17354570
[Indexed for MEDLINE]
33.
Expert Opin Emerg Drugs. 2005 Aug;10(3):521-36.

Autism spectrum disorders: emerging pharmacotherapy.

Author information

1
Harvard Medical School, Boston, MA, USA.

Abstract

Autism, Asperger and other pervasive developmental disorders (PDDs) are an increasingly commonly identified group of conditions wherein patients experience significant difficulty in social interactions, communicating with others, and inflexible adherence to unusual, unhelpful and frequently stereotyped routines and behaviour. These autism spectrum disorders are now being diagnosed earlier in life (approximately 15 months), and often remain a chronic, daily burden for those afflicted. In addition to the often profound impact on an individual's quality of life, the familial, social and economic burdens of PDDs can be enormous. No treatments are curative, and most pharmacological treatments are employed to treat specific troubling symptoms rather than the core features of the disorder itself. Therefore, more effective pharmacotherapies are desperately needed. This review describes current and emerging pharmacotherapies that may advance care of people with PDDs.

PMID:
16083327
DOI:
10.1517/14728214.10.3.521
[Indexed for MEDLINE]
Icon for Taylor & Francis
34.
Australas Psychiatry. 2005 Jun;13(2):173-5.

Lessons learnt in conducting a clinical drug trial in children with Asperger Syndrome.

Author information

1
Child and Adolescent Psychiatrist, Royal Children's Hospital, Mental Health Service, Parkville, Vic., Australia. john.mathai@rch.org.au

Abstract

OBJECTIVE:

To describe the authors' experience of conducting a clinical drug trial in children with Asperger Syndrome, including the pitfalls encountered and lessons learnt.

CONCLUSIONS:

The main barrier encountered was in the recruitment of children: it was not possible to recruit the target of 60 patients. The recruitment of children is often the major barrier to the progress of a successful clinical trial. Conducting the clinical drug trial was greatly facilitated by the appropriate setting and experienced clinical pharmacology staff.

[Indexed for MEDLINE]
Icon for Atypon
35.
Pediatrics. 2004 May;113(5):e472-86.

The genetics of autism.

Author information

1
Class of 2004, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Abstract

Autism is a complex, behaviorally defined, static disorder of the immature brain that is of great concern to the practicing pediatrician because of an astonishing 556% reported increase in pediatric prevalence between 1991 and 1997, to a prevalence higher than that of spina bifida, cancer, or Down syndrome. This jump is probably attributable to heightened awareness and changing diagnostic criteria rather than to new environmental influences. Autism is not a disease but a syndrome with multiple nongenetic and genetic causes. By autism (the autistic spectrum disorders [ASDs]), we mean the wide spectrum of developmental disorders characterized by impairments in 3 behavioral domains: 1) social interaction; 2) language, communication, and imaginative play; and 3) range of interests and activities. Autism corresponds in this article to pervasive developmental disorder (PDD) of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and International Classification of Diseases, Tenth Revision. Except for Rett syndrome--attributable in most affected individuals to mutations of the methyl-CpG-binding protein 2 (MeCP2) gene--the other PDD subtypes (autistic disorder, Asperger disorder, disintegrative disorder, and PDD Not Otherwise Specified [PDD-NOS]) are not linked to any particular genetic or nongenetic cause. Review of 2 major textbooks on autism and of papers published between 1961 and 2003 yields convincing evidence for multiple interacting genetic factors as the main causative determinants of autism. Epidemiologic studies indicate that environmental factors such as toxic exposures, teratogens, perinatal insults, and prenatal infections such as rubella and cytomegalovirus account for few cases. These studies fail to confirm that immunizations with the measles-mumps-rubella vaccine are responsible for the surge in autism. Epilepsy, the medical condition most highly associated with autism, has equally complex genetic/nongenetic (but mostly unknown) causes. Autism is frequent in tuberous sclerosis complex and fragile X syndrome, but these 2 disorders account for but a small minority of cases. Currently, diagnosable medical conditions, cytogenetic abnormalities, and single-gene defects (eg, tuberous sclerosis complex, fragile X syndrome, and other rare diseases) together account for <10% of cases. There is convincing evidence that "idiopathic" autism is a heritable disorder. Epidemiologic studies report an ASD prevalence of approximately 3 to 6/1000, with a male to female ratio of 3:1. This skewed ratio remains unexplained: despite the contribution of a few well characterized X-linked disorders, male-to-male transmission in a number of families rules out X-linkage as the prevailing mode of inheritance. The recurrence rate in siblings of affected children is approximately 2% to 8%, much higher than the prevalence rate in the general population but much lower than in single-gene diseases. Twin studies reported 60% concordance for classic autism in monozygotic (MZ) twins versus 0 in dizygotic (DZ) twins, the higher MZ concordance attesting to genetic inheritance as the predominant causative agent. Reevaluation for a broader autistic phenotype that included communication and social disorders increased concordance remarkably from 60% to 92% in MZ twins and from 0% to 10% in DZ pairs. This suggests that interactions between multiple genes cause "idiopathic" autism but that epigenetic factors and exposure to environmental modifiers may contribute to variable expression of autism-related traits. The identity and number of genes involved remain unknown. The wide phenotypic variability of the ASDs likely reflects the interaction of multiple genes within an individual's genome and the existence of distinct genes and gene combinations among those affected. There are 3 main approaches to identifying genetic loci, chromosomal regions likely to contain relevant genes: 1) whole genome screens, searching for linkage of autism to shared genetic markers in populations of multiplex families (families with >1 affected family member; 2) cytogenetic studies that may guide molecular studies by pointing to relevant inherited or de novo chromosomal abnormalities in affected individuals and their families; and 3) evaluation of candidate genes known to affect brain development in these significantly linked regions or, alternatively, linkage of candidate genes selected a priori because of their presumptive contribution to the pathogenesis of autism. Data from whole-genome screens in multiplex families suggest interactions of at least 10 genes in the causation of autism. Thus far, a putative speech and language region at 7q31-q33 seems most strongly linked to autism, with linkages to multiple other loci under investigation. Cytogenetic abnormalities at the 15q11-q13 locus are fairly frequent in people with autism, and a "chromosome 15 phenotype" was described in individuals with chromosome 15 duplications. Among other candidate genes are the FOXP2, RAY1/ST7, IMMP2L, and RELN genes at 7q22-q33 and the GABA(A) receptor subunit and UBE3A genes on chromosome 15q11-q13. Variant alleles of the serotonin transporter gene (5-HTT) on 17q11-q12 are more frequent in individuals with autism than in nonautistic populations. In addition, animal models and linkage data from genome screens implicate the oxytocin receptor at 3p25-p26. Most pediatricians will have 1 or more children with this disorder in their practices. They must diagnose ASD expeditiously because early intervention increases its effectiveness. Children with dysmorphic features, congenital anomalies, mental retardation, or family members with developmental disorders are those most likely to benefit from extensive medical testing and genetic consultation. The yield of testing is much less in high-functioning children with a normal appearance and IQ and moderate social and language impairments. Genetic counseling justifies testing, but until autism genes are identified and their functions are understood, prenatal diagnosis will exist only for the rare cases ascribable to single-gene defects or overt chromosomal abnormalities. Parents who wish to have more children must be told of their increased statistical risk. It is crucial for pediatricians to try to involve families with multiple affected members in formal research projects, as family studies are key to unraveling the causes and pathogenesis of autism. Parents need to understand that they and their affected children are the only available sources for identifying and studying the elusive genes responsible for autism. Future clinically useful insights and potential medications depend on identifying these genes and elucidating the influences of their products on brain development and physiology.

PMID:
15121991
[Indexed for MEDLINE]
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36.

Strategies for pharmacologic treatment of high functioning autism and Asperger syndrome.

Author information

1
Departments of Psychiatry and Behavioral Sciences, and Pediatrics, George Washington University School of Medicine, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA. Kenneth.Towbin@nih.gov

Abstract

The treatment of complex, polymorphous disorders like HFA/AS always brings a particular challenge to pharmacotherapy. Additionally, the specific characteristics presented by HFA/AS introduce unique complications to patient care and place unusual demands on a clinician's skill and experience. To provide safe and effective treatment, the clinician must understand the core features of the disorder and the manifestations of the condition in his or her patient. Furthermore, a thorough understanding of the family, school, and community resources and limitations is necessary. Once an assessment has been made, focusing on target symptoms provides a crucial framework for care. Knowing manifestations of symptoms and characterizing their distribution and behavior in that patient is most important. For patients with HFA/AS it is particularly essential to coordinate behavioral and pharmacologic objectives. The target symptoms should be tracked carefully and placed into a priority system that is based on the risks and disability they create for the patient. The skill of pharmacotherapy also means setting out realistic expectations, keeping track of the larger systems of care at school and home, and collaboration with parents and care providers. There is an expanding range and pace of biologic and intervention research into HFA/AS. The genetic work has produced exciting leads that are likely to be helpful to future generations [82-84], but the task of clinicians is to tend to today's patients. As we discover more about the complex neural circuitry subserving repetitive behaviors, reward systems, and social cognition, there are good reasons to believe our treatments will become more sophisticated and specific. Psychopharmacology is also moving to design medications that target more specific populations of receptor and brain functions. This is likely to produce medicines that have fewer side effects, are more effective, and are more symptom-specific. Pharmacotherapy is not the ultimate treatment for HFA/AS but it has a definite place. Medication can be a critical element in a comprehensive treatment plan. There is a wider range of medications with more specific biologic effects than ever before. For patients with HFA/AS these newer agents are safer and less disruptive. When paired with clinicians who are becoming more skilled at recognizing and managing symptoms, patients have a greater opportunity to reach their potential and lead pleasurable lives.

PMID:
12512397
[Indexed for MEDLINE]
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38.
Lijec Vjesn. 1963 Oct;85:1162-4.

[PLACEBOS AND THE CLINICAL EVALUATION OF DRUGS].

[Article in Undetermined Language]
PMID:
14097622
[Indexed for MEDLINE]

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