Diagnosis of autism and other pervasive developmental disorders

Problems in the diagnosis of autism and other pervasive developmental disorders are reviewed. Modification and application of recent developments in neuroimaging, molecular genetics and population studies are presented. A prioritized list of needed investigations is discussed.     

Differential diagnosis between schizophrenia and autism in adulthood: A case report

The clinical distinction between autism spectrum disorders (ASD), also called pervasive developmental disorders (PDD), and schizophrenia is often difficult to make. Here we describe a case of an adult patient presenting with a diagnosis of schizophrenia based on a history of functional deterioration and presumed persecutory delusions. A psychiatric and psychological assessment conducted from a developmental perspective, in association with direct observation and neuropsychological evaluation for intellectual disabilities and autism, led to a diagnosis of PDD not otherwise specified, with revision of the initial diagnosis of schizophrenia.     

When does the Autism Spectrum Screening Questionnaire (ASSQ) predict autism spectrum disorders in primary school-aged children?

The aims of this study were, firstly, to study the association between parents’ and teachers’ ratings for the Finnish version of the Autism Spectrum Screening Questionnaire (ASSQ), secondly, to find out whether the original cut-off scores of the ASSQ identify primary school-aged children with Asperger syndrome (AS) or autism by using the Finnish ASSQ, and thirdly, to evaluate the validity of the ASSQ. Parents and/or teachers of higher-functioning (full-scale intelligence quotient ≥ 50) 8-year-old total population school children (n = 4,408) and 7–12-year-old outpatients with AS/autism (n = 47) completed the Finnish version of the ASSQ. Agreement between informants was slight. In the whole total population, low positive correlation was found between parents’ and teachers’ ratings, while in the sample of high-scoring children the correlation turned out to be negative. A cut-off of 30 for parents’ and teacher's summed score and 22 for teachers’ single score is recommended. A valid cut-off for parents’ single score could not been estimated. The clinicians are reminded that the ASSQ is a screening instrument, not a diagnosing instrument. The importance of using both parents’ and teachers’ ratings for screening in clinical settings is underlined.     

Psychiatric Symptoms and Psychosocial Difficulties in Young Adults with Autistic Traits

A screening version of the social responsiveness scale (SRS) was administered to 1,847 university students to identify a subgroup reporting significantly greater autism traits relative to their peers (High SRS group). A group reporting minimal autism traits was also identified (Low SRS group) matched for age, gender, and attentional difficulties. We administered the Behavioral Assessment System for Children—2nd edition (BASC-2), a comprehensive questionnaire designed to assess psychiatric symptoms and personality characteristics, to both groups. The high SRS group reported significantly more difficulties across the majority of areas, including depression/anxiety, interpersonal relationships, and personal adjustment. Thus, young adults reporting a greater degree of autistic traits also reported greater psychiatric difficulties across a wide psychosocial range.     

Adults with Autism Spectrum Disorders using psychiatric hospitals in Ontario: Clinical profile and service needs

BackgroundAdults with Autism Spectrum Disorders (ASD) represent a small, but challenging sub-group of patients within Ontario's mental health care system. However, few studies have documented the clinical characteristics of this population and examined how such individuals differ from other psychiatric patients, with or without intellectual disabilities (ID).MethodA secondary analysis of data from the 2003 Comprehensive Assessment Projects from three psychiatric hospitals in Ontario was conducted to describe patients with ASD and ID and to determine how their profile compared to other hospital users.ResultsTwenty-three patients with ASD and ID were matched on gender and patient status (inpatient/outpatient) to individuals with and without ID. Individuals with ASD and ID were similar in terms of demographics to patients with and without ID. However, individuals with ASD and ID were younger, spent more days in hospital and were less likely to have a psychotic disorder diagnosis than both patients with and without ID. Inpatients with ASD and ID were recommended for a higher level of care than hospital service users without ID.ConclusionsClearly, this small sub-group of individuals within the hospital population has high clinical needs that are not always well met.     

Psychopathology in Adults with Autism and Intellectual Disability

There have been few studies of psychopathology in adult with autism. This study examined psychiatric co-morbidity in 147 adults with intellectual disability (ID) and autism and 605 adults with ID but without autism. After controlling for the effects of gender, age, psychotropic medication and level of ID, people with autism and ID were no more likely to receive a psychiatric diagnosis than people with ID only. People with autism were less likely to receive a diagnosis of personality disorder. These findings cast doubts on the hypothesis that adults with ID and autism are more vulnerable to certain psychiatric disorders than non-autistic adults with ID.     

Cortical activation during attention to sound in autism spectrum disorders

Individuals with autism spectrum disorders (ASDs) can demonstrate hypersensitivity to sounds as well as a lack of awareness of them. Several functional imaging studies have suggested an abnormal response in the auditory cortex of such subjects, but it is not known whether these subjects have dysfunction in the auditory cortex or are simply not listening. We measured changes in blood oxygenated hemoglobin (OxyHb) in the prefrontal and temporal cortices using near-infrared spectroscopy during various listening and ignoring tasks in 11 ASD and 12 control subjects. Here we show that the auditory cortex in ASD subjects responds to sounds fully during attention. OxyHb in the auditory cortex increased with intentional listening but not with ignoring of the same auditory stimulus in a similar fashion in both groups. Cortical responses differed not in the auditory but in the prefrontal region between the ASD and control groups. Thus, unawareness to sounds in ASD could be interpreted as due to inattention rather than dysfunction of the auditory cortex. Difficulties in attention control may account for the contrary behaviors of hypersensitivity and unawareness to sound in ASD.     

The GLO1 C332 (Ala111) allele confers autism vulnerability: Family-based genetic association and functional correlates

Glyoxalase I (GLO1) is a homodimeric Zn²⁺-dependent isomerase involved in the detoxification of methylglyoxal and in limiting the formation of advanced glycation end-products (AGE). We previously found the rs4746 A332 (Glu111) allele of the GLO1 gene, which encodes for glyoxalase I, associated with “unaffected sibling” status in families with one or more children affected by Autism Spectrum Disorder (ASD). To identify and characterize this protective allele, we sequenced GLO1 exons and exon–intron junctions, detecting two additional SNPs (rs1049346, rs1130534) in linkage disequilibrium with rs4746. A family-based association study involving 385 simplex and 20 multiplex Italian families yielded a significant association with autism driven only by the rs4746 C332 (Ala111) allele itself (P < 0.05 and P < 0.001 under additive and dominant/recessive models, respectively). Glyoxalase enzymatic activity was significantly reduced both in leukocytes and in post-mortem temporocortical tissue (N = 38 and 13, respectively) of typically developing C332 allele carriers (P < 0.05 and <0.01), with no difference in Glo1 protein levels. Conversely, AGE amounts were significantly higher in the same C332 post-mortem brains (P = 0.001), with a strong negative correlation between glyoxalase activity and AGE levels (τ = −0.588, P < 0.01). Instead, 19 autistic brains show a dysregulation of the glyoxalase-AGE axis (τ = −0.209, P = 0.260), with significant blunting of glyoxalase activity and AGE amounts compared to controls (P < 0.05), and loss of rs4746 genotype effects. In summary, the GLO1 C332 (Ala111) allele confers autism vulnerability by reducing brain glyoxalase activity and enhancing AGE formation, but years after an autism diagnosis the glyoxalase-AGE axis appears profoundly disrupted, with loss of C332 allelic effects.     

Reliability and validity of the SPAID-G checklist for detecting psychiatric disorders in adults with intellectual disability

SPAID (Psychiatric Instrument for the Intellectually Disabled Adult) is the first Italian tool-package for carrying out psychiatric diagnosis in adults with Intellectual Disabilities (ID). It includes the “G” form, for general diagnostic orientation, and specific checklists for all groups of syndromes stated by the available classification systems. SPAID was established to provide an easy and quick tool for daily practice of the personnel working with ID. The present study was aimed at evaluating psychometric and psychodiagnostic characteristics of the SPAID-G and at supplying new data on the prevalence rate of psychiatric disorders in a multicentric Italian sample of people with ID living in different settings. The SPAID-G was randomly applied to 304 participants with ID attending residential facilities or assessment services across Italy. A part of the sample was also consecutively assessed through the use of DASH, PDD-MRS and by the clinical application of the DSM-IV TR criteria. The correlation between SPAID-G scores and those provided by other evaluation tools was over 60%. Additionally, the internal consistency and inter-rater reliability resulted to be good. Psychopathological symptoms were detected in approximately 40% of the sample. Respectively, autistic spectrum disorders, impulse control disorders, mood disorders, and dramatic personality disorders were the diagnostic orientations providing the most prevalent over-threshold scores. SPAID-G seems to be a valid diagnostic tool, quick and easy to use in psychiatric disorders assessment within the Italian population with ID.     

The association between the social and communication elements of autism, and repetitive/restrictive behaviours and activities: A review of the literature

Research continues to try and pinpoint the etiological role of particular genes and brain structure in autistic spectrum disorder (ASD), but despite a host of biological, genetic and neuropsychological research, the symptom profile of pervasive developmental disorders (PDDs) are not yet linked to etiological theory. Debate continues around whether or not there is one single dimension that incorporates the three criteria domains of social difficulties, communication deficits and repetitive or restrictive interests and behaviours as a unitary ‘ASD’ concept, or whether PDD as they are currently described represent the co-occurence of separate sub-domains of developmental difficulties. Although the three criteria need to be met for a diagnosis of PDD to be made, the association between them remains unclear. This review highlights that the majority of the literature that looks at the triad of impairments suggests the symptom structure does not match that proposed by diagnostic manuals, and that the triad may no longer fit as the best way to conceptualise ASD.     

Infant head growth in male siblings of children with and without autism spectrum disorders

Previous research has indicated that children with autism exhibit accelerated head growth (HG) in infancy, although the timing of acceleration varies between studies. We examined infant HG trajectory as a candidate autism endophenotype by studying sibling pairs. We retrospectively obtained serial head orbitofrontal circumference measurements of: a) 48 sibling pairs in which one (n = 28) or both (n = 20) sibs were affected by an autism spectrum disorder (ASD); and b) 85 control male sibling pairs. Rate of HG of ASD subjects was slightly accelerated compared to controls, but the magnitude of difference was below the limit of reliability of standard measurement methods. Sibling intra class correlation for rate of HG was highly statistically significant; the magnitude was significantly stronger among autism-affected families (ICC = .63) than among controls (ICC = .26), p < .01. Infant HG trajectory appears familial—possibly endophenotypic—but was not a reliable marker of autism risk among siblings of ASD probands in this sample.     

A prospective case control study of psychiatric disorders in adults with epilepsy and intellectual disability

Purpose: No study to date has prospectively investigated the impact of epilepsy on psychiatric disorders among adults with an intellectual disability (ID). This study aimed to determine prospectively the influence of epilepsy on the development of psychiatric disorders in adults with ID. Method: Psychiatric symptoms were measured prospectively over a 1‐year period among 45 adults with ID and active epilepsy and 45 adults with ID without epilepsy, matched on level of ID. The 1‐year incidence rate (IR) of commonly occurring Axis 1 psychiatric disorders was compared with and without controlling for possible confounding factors. Total psychiatric symptom scores over the period were compared between the two groups using repeated‐measures analysis of covariance. Key Findings: Adults with epilepsy and ID had a more than seven times increased risk for developing psychiatric disorders, particularly depression and unspecified disorders of presumed organic origin, including dementia, over a 1‐year period compared to those with ID only. Comparison of the psychiatric scores showed the epilepsy group to have significantly higher unspecified disorder and depression symptom scores. Significance: The findings point to an increased risk of depression and unspecified disorders, including dementia, among adults with ID and epilepsy. Further exploration of the nature and treatment of these unspecified disorders may help the care of people with epilepsy and ID.     

Gastrointestinal Symptoms in a Sample of Children with Pervasive Developmental Disorders

Objective To evaluate gastrointestinal (GI) problems in a large, well-characterized sample of children with pervasive developmental disorders (PDDs). Methods One hundred seventy two children entering one of two trials conducted by the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network were assessed comprehensively prior to starting treatment and classified with regard to GI symptoms. Results Thirty nine (22.7%) were positive for GI problems, primarily constipation and diarrhea. Those with GI problems were no different from subjects without GI problems in demographic characteristics, measures of adaptive functioning, or autism symptom severity. Compared to children without GI problems, those with GI problems showed greater symptom severity on measures of irritability, anxiety, and social withdrawal. Those with GI problems were also less likely to respond to treatment.     

The broad autism phenotype predicts child functioning in autism spectrum disorders

Background

Broad autism phenotype (BAP) is a milder expression of the social and communication impairments seen in autism spectrum disorders (ASD). While prior studies characterized the BAP in unaffected family members of probands with ASD, the relationship between parental BAP traits and proband symptomatology remains poorly understood. This study utilizes the Broad Autism Phenotype Questionnaire (BAPQ) in parents and the Social Responsiveness Scale (SRS) in children to examine this connection. We hypothesized that in families affected by ASD, elevated maternal and paternal BAPQ scores would correlate with greater autism symptomatology in diagnosed children. In an extension of prior research, we also explored this relationship in families with typically developing children (TDC).

Methods

Two hundred and forty-five children with ASD, 129 TDC and all parents were recruited as part of a larger study investigating relationships between genes, brain and behavior. The Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS) and expert clinical judgment confirmed ASD diagnoses in children. SRS was collected for all children. Parents completed a self-report BAPQ and an informant report BAPQ for their spouse; an average of self-report and informant report for each parent was used in all analyses.

Results

Mothers and fathers of children with ASD had significantly higher rates of BAP traits as compared to parents of TDC. Maternal and paternal BAPQ total scores were not correlated with child IQ in either group. In the ASD group, 10% of mothers and 21% of fathers scored above the established BAP threshold compared to 4% of TDC parents. Crude regression analyses showed that maternal and paternal BAPQ total scores accounted for significant variance in child SRS scores in both ASD (17.1%) and TDC (19.8%) families.

Conclusions

Our results suggest that broad autism symptomatology in parents is moderately associated with their child’s autism symptomatology. This result extended to TDC families, suggesting that the BAPQ and SRS capture subtle, subclinical social variation in both children and adults. These findings could help define multi-generational social impairments in future phenotypic and genetic studies.     

Gender-related differences in the associations between sexual impulsivity and psychiatric disorders

ObjectiveSexual impulsivity (SI) has been associated with conditions that have substantial public health costs, such as sexually transmitted infections and unintended pregnancies. However, SI has not been examined systematically with respect to its relationships to psychopathology. We aimed to investigate associations between SI and psychopathology, including gender-related differences.MethodWe performed a secondary data analysis of Wave-2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a national sample of 34,653 adults in the United States. DSM-IV-based diagnoses of mood, anxiety, drug and personality disorders were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Scheduled DSM-IV Version.ResultsThe prevalence of SI was considerable (14.7%), with greater acknowledgment by men than women (18.9% versus 10.9%; p < 0.0001). For both women and men, SI was positively associated with most Axis-I and Axis-II psychiatric disorders (OR range: Women, Axis-I:1.89–6.14, Axis-II:2.10–10.02; Men, Axis-I:1.92–6.21, Axis-II:1.63–6.05). Significant gender-related differences were observed. Among women as compared to men, SI was more strongly associated with social phobia, alcohol abuse/dependence, and paranoid, schizotypal, antisocial, borderline, narcissistic, avoidant and obsessive-compulsive personality disorders.ConclusionThe robust associations between SI and psychopathology across genders suggest the need for screening and interventions related to SI for individuals with psychiatric concerns. The stronger associations between SI and psychopathology among women as compared to men emphasize the importance of a gender-oriented perspective in targeting SI. Longitudinal studies are needed to determine the extent to SI predates, postdates or co-occurs with specific psychiatric conditions.     

Seizures and epilepsy and their relationship to autism spectrum disorders

Autism spectrum disorders (ASD) are serious neurodevelopmental disorders which often co-occur with intellectual disabilities. A disorder which is strongly correlated with both of these disabilities are seizures and epilepsy. The purpose of this review was to provide an overview of available research on seizures and epilepsy in the ASD population and to provide a status report on recent trends in research. Among these topics are prevalence, nosology, etiology, and autistic regression. Strengths and weaknesses of the current, available literature are discussed.     

Retrospective case series of aripiprazole augmentation in pervasive developmental disorders

Due to co-morbidities and treatment resistant nature of pervasive developmental disorder (PDD), diverse combinations of regimens have been tried. This retrospective study aimed to explore adjunctive use of aripiprazole in children with PDD. Changes in illness severity were measured by Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) in 14 aripiprazole-treated patients with PDD. Improvement of illness severity was observed after aripiprazole add-on (5.8±0.8 to 4.9±1.0, Z=-2.75, p=0.001). Mean dosage was 7.7 mg/day [standard deviation (SD) 3.3, range 5-15]. A higher mean dosage was observed in group with improvement in symptoms (t=-2.33, df =12, p=0.004). The target symptoms most effectively improved after using aripiprazole were positive psychotic symptoms (mean CGI-I: 2.0±1.4, 3 responders/4 patients, 75% response) followed by aggressive behavior (2.5±1.7, 3/4, 75%), self-injurious behavior (2.0±1.0, 2/3, 67%), stereotypic behavior (2.7±1.2, 2/3, 67%), tic (2.8±1.0, 2/4, 50%), irritability (3.5±2.1, 1/2, 50%), obsessive behavior (2.5±2.1, 1/3, 33%), hyperactivity (3.4±1.6, 3/7, 43%) and mood fluctuation (3, 0/1, no response). Five patients (35%) discontinued aripiprazole due to treatment-emergent adverse effects (akathisia, insomnia, withdrawal). The results of this study suggest that aripiprazole augmentation may be used safely in maladaptive behaviors of some populations of PDD. However, future studies are required to confirm these preliminary findings.     

The Prevalence and Incidence of Mental Ill-Health in Adults with Autism and Intellectual Disabilities

The prevalence, and incidence, of mental ill-health in adults with intellectual disabilities and autism were compared with the whole population with intellectual disabilities, and with controls, matched individually for age, gender, ability-level, and Down syndrome. Although the adults with autism had a higher point prevalence of problem behaviours compared with the whole adult population with intellectual disabilities, compared with individually matched controls there was no difference in prevalence, or incidence of either problem behaviours or other mental ill-health. Adults with autism who had problem behaviours were less likely to recover over a two-year period than were their matched controls. Apparent differences in rates of mental ill-health are accounted for by factors other than autism, including Down syndrome and ability level.

Positive Effects of Methylphenidate on Social Communication and Self-Regulation in Children with Pervasive Developmental Disorders and Hyperactivity

This report examined the effect of methylphenidate on social communication and self-regulation in children with pervasive developmental disorders and hyperactivity in a secondary analysis of RUPP Autism Network data. Participants were 33 children (29 boys) between the ages of 5 and 13 years who participated in a four-week crossover trial of placebo and increasing doses of methylphenidate given in random order each for one week. Observational measures of certain aspects of children’s social communication, self-regulation, and affective behavior were obtained each week. A significant positive effect of methylphenidate was seen on children’s use of joint attention initiations, response to bids for joint attention, self-regulation, and regulated affective state. The results go beyond the recent literature and suggest that methylphenidate may have positive effects on social behaviors in children with PDD and hyperactivity.