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Three phase 2 trials were conducted to assess the efficacy and long-term safety of weight-based memantine extended release (ER) treatment in children with autism spectrum disorder. MEM-MD-91, a 50-week open-label trial, identified memantine extended-release treatment responders for enrollment into MEM-MD-68, a 12-week randomized, double-blind, placebo-controlled withdrawal trial. MEM-MD-69 was an open-label extension trial in which participants from MEM-MD-68, MEM-MD-91, and open-label trial MEM-MD-67 were treated ⩽48 weeks with memantine extended release. In MEM-MD-91, 517 (59.6%) participants were confirmed Social Responsiveness Scale responders at week 12; mean Social Responsiveness Scale total raw scores improved two to three times a minimal clinically important difference of 10 points. In MEM-MD-68, there was no difference between memantine and placebo on the primary efficacy parameter, the proportion of patients with a loss of therapeutic response (defined as ⩾10-point increase from baseline in Social Responsiveness Scale total raw score). MEM-MD-69 exploratory analyses revealed mean standard deviation improvement in Social Responsiveness Scale total raw score of 32.4 (26.4) from baseline of the first lead-in study. No new safety concerns were evident. While the a priori-defined efficacy results of the double-blind trial were not achieved, the considerable improvements in mean Social Responsiveness Scale scores from baseline in the open-label trials were presumed to be clinically important.

OBJECTIVES: Pervasive developmental disorders (PDDs) are neurodevelopmental disorders characterized by deficits in social interactions, communication impairments, and the presence of restricted interests and stereotyped behaviours. The issue of diagnostic stability, course, and prognosis of PDDs is an increasing focus of research studies. The aim of this study is to evaluate the individuals who were previously diagnosed with pervasive developmental disorders–not otherwise specified (PDD–NOS) (one of the sub-diagnoses of PDDs) under age six years with respect to their current diagnoses. METHODS: The participants were selected among the patients who were diagnosed with PDD–NOS under six years of age in our outpatient clinic. We obtained 208 patients’ file records. We were able to reach 92 patients’ parent by telephone and 58 parents accepted to voluntarily participate. After the excluded cases, finally 51 patients were evaluated in this cross-sectional naturalistic follow-up study. Children Autism Rating Scale (CARS) and Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS) were administered to participants; Autism Behavior Checklist (ABC) was completed by their parents. RESULTS: There were 44 (86.3%) male and 7 (13.7%) female participants in the study. The current mean age was 8.62 years (SD = 2.25). The mean age at the time of first diagnosis was 3.56 years (SD = 1.22). The mean duration of the follow-up period was 5.05 years (SD = 2.27). Forty-five (88.2%) of 51 patients remained to have one of the PDDs (23 autistic disorder, 22 PDD–NOS) according to DSM-IV-TR. Six patients (11.8%) did not meet the diagnostic criteria of any PDDs. Two of these six patients diagnosed with attention-deficit/hyperactivity disorder and one with mild-level intellectual disability. CONCLUSIONS: It was observed that 11.8% patients who diagnosed as PDD–NOS less than six years old were found to be off the PDD spectrum. PDD–NOS diagnosis stability was found 43.1% and 45.1% of the patients moved to another PDD diagnosis. These findings should be supported with further studies in Turkey, by increasing sample size, and follow-up duration for understanding the course.

Autism is an etiologically heterogeneous developmental disorder for which the range of genetic investigations has expanded considerably over the past decade. Introduction of chromosomal microarray (CMA) to clinical practice has expanded the range of conditions which pediatricians are able to detect. This study reviewed the utilization, yield and cost of genetic investigations in a sample of children with pervasive developmental disorders (PDD) in an Australian metropolitan child development service. Six hundred and ninety eight patients with PDD were identified from the clinic population. One hundred and ten (15.7%) of the clinic population had undergone investigation with chromosomal microarray, 140 (20.0%) with karyotype (KT), and 167 (23.9%) with Fragile X testing (FRGX). Twelve (10.9%) CMA findings were reported, of which seven (6.3%) were felt to be the likely cause of the child’s clinical features. Five (3.5%) KT findings were reported, of which four (2.9%) were felt to be the likely cause of the child’s clinical features. Two patients (1.2%) were identified with Fragile X expansions. One fifth of the clinic’s recent PDD population had undergone testing with CMA. CMA appears to have increased the diagnostic yield of the genetic investigation of autism, in line with internationally reported levels. Number needed to test (NNT) and cost per incremental diagnosis, were also in line with internationally reported levels.

The existing data demonstrate a significant interrelation between ASD and essential and toxic trace elements status of the organism. However, data on trace element homeostasis in particular ASD forms are insufficient. Therefore, the objective of the present study was to assess the level of trace elements and electrolytes in serum of children with childhood and atypical autism. A total of 48 children with ASD (24 with childhood and 24 with atypical autism) and age- and sex-adjusted controls were examined. Serum trace elements and electrolytes were assessed using inductively-coupled plasma mass spectrometry. The obtained data demonstrate that children with ASD unspecified are characterized by significantly lower Ni, Cr, and Se levels as compared to the age- and sex-matched controls. At the same time, significantly decreased serum Ni and Se concentrations were detected in patients with childhood autism. In turn, children with atypical autism were characterized by more variable serum trace element spectrum. In particular, atypical autism is associated with lower serum Al, As, Ni, Cr, Mn, and Se levels in comparison to the control values. Moreover, Al and Mn concentration in this group was also lower than that in childhood autism patients. Generally, the obtained data demonstrate lower levels of both essential and toxic trace elements in atypical autism group, being indicative of profound alteration of trace elements metabolism. However, further detailed metabolic studies are required to reveal critical differences in metabolic pathways being responsible for difference in trace element status and clinical course of the disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically developing children (age 9–16 years) were included at baseline and followed up approximately 25 months later. The children were given a letter/number sequencing task to assess verbal working memory. The performance of children with high-functioning autism on verbal working memory did not improve after 2 years, while improvement was observed in children with attention-deficit/hyperactivity disorder and typically developing children. The results indicate a different developmental trajectory for verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. More research is needed to construct a developmental framework more suitable for children with autism spectrum disorder. [ABSTRACT FROM PUBLISHER]

Background The present study aims to examine if autism spectrum disorder (ASD) is a risk factor for suicide attempts among adult depressed patients and to elucidate the characteristics of suicide attempts in adult depressed patients with ASD. Methods We conducted a case-control study. Subjects consisted of 336 retrospectively recruited first-time visit patients to our outpatient clinic with a current major depressive episode; 31 of the 336 patients had attempted suicide. The demographic backgrounds (i.e., age, gender, personal/family history of suicidality); specific psychopathology like bipolarity, agitation, and psychotic features; and comorbidity such as physical diseases, alcohol abuse, cluster B personality disorder, and ASD including pervasive developmental disorder not otherwise specified (PDD-NOS) were examined as potential risk factors for suicide attempts. We compared these variables between the suicide attempters and non-attempters. In addition, we compared suicide attempters to non-attempters within the ASD group and non-ASD group. Binary logistic regression analysis was performed using the significant independent variables from the comparisons between the suicide attempters and non-attempters, and the odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results Logistic regression analysis demonstrated that agitation during a depressive episode (OR =7.15, 95% CI =2.88-17.74), past suicidal behaviors (OR =4.32, 95% CI =1.70-10.98), and comorbid PDD-NOS (OR =4.04, 95% CI =1.20-13.54) were significantly associated with suicide attempts. The most prevalent suicidal method was drug overdose (59.1%) among non- ASD attempters while hanging was the most prevalent (44.4%) in ASD attempters. Conclusions Depressed adults with comorbid atypical autistic traits are at higher risk for suicide attempts and may engage in methods that are more lethal. [ABSTRACT FROM AUTHOR]

Background: It has long been debated whether Asperger's Syndrome (ASP) should be considered part of the Autism Spectrum Disorders (ASD) or whether it constitutes a unique entity. The Diagnostic and Statistical Manual, fourth edition (DSM-IV) differentiated ASP from high functioning autism. However, the new DSM-5 umbrellas ASP within ASD, thus eliminating the ASP diagnosis. To date, no clear biomarkers have reliably distinguished ASP and ASD populations. This study uses EEG coherence, a measure of brain connectivity, to explore possible neurophysiological differences between ASP and ASD. Methods: Voluminous coherence data derived from all possible electrode pairs and frequencies were previously reduced by principal components analysis (PCA) to produce a smaller number of unbiased, data-driven coherence factors. In a previous study, these factors significantly and reliably differentiated neurotypical controls from ASD subjects by discriminant function analysis (DFA). These previous DFA rules are now applied to an ASP population to determine if ASP subjects classify as control or ASD subjects. Additionally, a new set of coherence based DFA rules are used to determine whether ASP and ASD subjects can be differentiated from each other. Results: Using prior EEG coherence based DFA rules that successfully classified subjects as either controls or ASD, 96.2% of ASP subjects are classified as ASD. However, when ASP subjects are directly compared to ASD subjects using new DFA rules, 92.3% ASP subjects are identified as separate from the ASD population. By contrast, five randomly selected subsamples of ASD subjects fail to reach significance when compared to the remaining ASD populations. When represented by the discriminant variable, both the ASD and ASD populations are normally distributed. Conclusions: Within a control-ASD dichotomy, an ASP population falls closer to ASD than controls. However, when compared directly with ASD, an ASP population is distinctly separate. The ASP population appears to constitute a neurophysiologically identifiable, normally distributed entity within the higher functioning tail of the ASD population distribution. These results must be replicated with a larger sample given their potentially immense clinical, emotional and financial implications for affected individuals, their families and their caregivers. [ABSTRACT FROM AUTHOR]

Abstract: This study was designed to identify specific difficulties and associated features related to the problems with social interaction experienced by individuals with pervasive developmental disorder-not otherwise specified (PDD-NOS) using an emotion-recognition task. We compared individuals with PDD-NOS or Asperger''s disorder (ASP) and typically developing individuals in terms of their ability to recognize facial expressions conveying the six basic emotions. Individuals with PDD-NOS and ASP were worse at recognizing fearful faces than were controls. Individuals with PDD-NOS were less accurate in recognizing disgusted faces than were those with ASP. The results suggest that PDD subtypes are characterized by shared and unique impairments in the ability to recognize facial expressions. Furthermore, the ability to recognize fearful but not disgusted expressions was negatively correlated with the severity of social dysfunction in PDD-NOS and ASP. The results suggest that impaired recognition of fearful and disgusted faces may reflect the severity of social dysfunction across PDD subtypes and the specific problems associated with PDD-NOS, respectively. Characteristics associated with different levels of symptom severity in PDD-NOS are discussed in terms of similarities with brain damage and other psychiatric disorders. [Copyright &y& Elsevier]

Previous research has found that individuals with intellectual disability and/or autism spectrum disorder (ASD), and those with greater symptom severity within these diagnoses, show higher rates of aggressive/destructive behavior, stereotypic behavior, and self-injurious behavior. In this exploratory cross-sectional study, toddlers at-risk for a developmental disorder (n =1509) ranging from 17 to 36 months fell into one of three diagnostic categories: Autistic Disorder, Pervasive Developmental Disorder-Not Otherwise Specified [PDD-NOS], and atypically developing – no ASD diagnosis. Mental health professionals from EarlySteps, Louisiana''s Early Intervention System, interviewed parents and guardians using the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT) –Part 3 () to obtain measures of challenging behaviors and the Battelle Developmental Inventory, 2nd Edition (BDI-2) () to obtain developmental quotients (DQ). Toddlers diagnosed with Autistic Disorder or PDD-NOS showed a positive relationship between total DQ and challenging behavior; whereas, atypically developing toddlers with no ASD diagnosis showed a more adaptive, negative relationship. The DQ domains that were most influential on challenging behaviors varied by diagnosis, with communication and motor domains playing greater roles for toddlers with Autistic Disorder or PDD-NOS, and personal–social and cognitive domains playing greater roles for atypically developing toddlers with no ASD diagnosis. [Copyright &y& Elsevier]

The authors’ purpose in this report is to examine the application of general-case programming to teach collateral academic skills to a student with pervasive developmental disorder–not otherwise specified (PDD-NOS) and with a mild intellectual disability who was attending college. The authors use data drawn from their work with Tom to explain and illustrate how a general-case approach may be developed and implemented effectively. The authors’ experience provides initial support for the utility of general-case programming for teaching acquisition and generalization of collateral academic skills. They make recommendations to guide researchers in future investigations of the application of the general-case programming to teach skills that enhance the successful integration of students with disabilities in postsecondary programs. [ABSTRACT FROM PUBLISHER]

We describe our experience in using melatonin to treat insomnia, a common sleep concern, in children with autism spectrum disorders. One hundred seven children (2-18 years of age) with a confirmed diagnosis of autism spectrum disorders who received melatonin were identified by reviewing the electronic medical records of a single pediatrician. All parents were counseled on sleep hygiene techniques. Clinical response to melatonin, based on parental report, was categorized as (1) sleep no longer a concern, (2) improved sleep but continued parental concerns, (3) sleep continues to be a major concern, and (4) worsened sleep. The melatonin dose varied from 0.75 to 6 mg. After initiation of melatonin, parents of 27 children (25%) no longer reported sleep concerns at follow-up visits. Parents of 64 children (60%) reported improved sleep, although continued to have concerns regarding sleep. Parents of 14 children (13%) continued to report sleep problems as a major concern, with only 1 child having worse sleep after starting melatonin (1%), and 1 child having undetermined response (1%). Only 3 children had mild side-effects after starting melatonin, which included morning sleepiness and increased enuresis. There was no reported increase in seizures after starting melatonin in children with pre-existing epilepsy and no new-onset seizures. The majority of children were taking psychotropic medications. Melatonin appears to be a safe and well-tolerated treatment for insomnia in children with autism spectrum disorders. Controlled trials to determine efficacy appear warranted. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical characteristics of children given a diagnosis of pervasive developmental disorder-not otherwise specified (PDD-NOS) by expert clinicians and to compare these to the clinical characteristics of children given a diagnosis of autism and Asperger syndrome (AS). Method: Two hundred sixteen children with autism, 33 with AS, and 21 with PDD-NOS were compared on measures of level of functioning (communication, daily living and social skills, IQ, and age of acquisition of language) and on various symptoms of autism (impaired communication and reciprocal social interaction and a preference for repetitive and stereotyped activities). Results: In terms of level of functioning measures, the PDD-NOS children had scores that were between those of the children with autism and those of the children with AS. In contrast, the PDD-NOS group had fewer autistic symptoms, especially repetitive stereotyped behaviors, than both the autism and AS groups (χ2 = 11.06, p = .004). Children with PDD-NOS could be placed into one of three subgroups: a high-functioning group (24%) who resembled AS but had transient language delay or mild cognitive impairment; a subgroup resembling autism (24%) but who had late age of onset or too severe cognitive delays or were too young to potentially meet the full diagnostic criteria for autism; and a group (52%) not fulfilling the criteria for autism because of fewer stereotyped and repetitive behaviors. Conclusions: With some revision to current diagnostic criteria, a more homogenous atypical group with significant impairments in social-communication but fewer repetitive behaviors can be differentiated from the more nonspecific PDD-NOS group. This differentiation may lead to better reliability in diagnosis and to further progress in studies of etiology. [ABSTRACT FROM AUTHOR]

Little information is available regarding the yield of the medical evaluation of children diagnosed with pervasive developmental disorder–not otherwise specified (PDD-NOS) compared to children diagnosed with autistic disorder. Medical records were reviewed for 182 patients less than 18 years of age with either PDD-NOS or autistic disorder evaluated between 1994 and 1998 at Mayo Clinic. A condition likely to be etiologically relevant was identified in 6/117 (5.1%) patients diagnosed with PDD-NOS and 2/65 (3.1%) patients diagnosed with autistic disorder. Genetic disorders, both chromosomal and single-gene, were the most commonly identified conditions. Seizure disorders, electroencephalogram abnormalities, and anomalies on brain imaging were common in both groups. The likelihood of uncovering an etiologically relevant condition in children diagnosed with either PDD-NOS or autistic disorder may be equivalent. The scope of the etiological search in an individual patient with an autistic spectrum disorder should not be limited by the specific diagnostic category. [ABSTRACT FROM AUTHOR]

Suicide is a major problem in Western society. However we have very little understanding of suicidal behaviour among individuals with autism spectrum disorders. The purpose of this review is to synthesise primary research on suicidal behaviour among adolescents and young adults with autism spectrum disorders in order to estimate prevalence and to identify and critically evaluate risk factors for suicidal behaviour in this population. Four primary research studies were identified for this review following a comprehensive literature search. The available research provides little empirical evidence for the processes underlying suicidal behaviour in adolescents and young adults with autism., (© 2013.)

Children with autism spectrum disorder (ASD) and age-matched typically-developing (TD) peers were tested on two forms of eyeblink conditioning (EBC), a Pavlovian associative learning paradigm where subjects learn to execute an appropriately-timed eyeblink in response to a previously neutral conditioning stimulus (CS). One version of the task, trace EBC, interposes a stimulus-free interval between the presentation of the CS and the unconditioned stimulus (US), a puff of air to the eye which causes the subjects to blink. In delay EBC, the CS overlaps in time with the delivery of the US, usually with both stimuli terminating simultaneously. ASD children performed normally during trace EBC, exhibiting no differences from TD subjects with regard to the learning rate or the timing of the conditioned response. However, when subsequently tested on delay EBC, subjects with ASD displayed abnormally-timed conditioned eye blinks that began earlier and peaked sooner than those of TD subjects, consistent with previous findings. The results suggest an impaired ability of children with ASD to properly time conditioned eye blinks which appears to be specific to delay EBC. We suggest that this deficit may reflect a dysfunction of the cerebellar cortex in which increases in the intensity or duration of sensory input can temporarily disrupt the accuracy of motor timing over short temporal intervals., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)