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1.  Investigating the efficacy of integrated cognitive behavioral therapy for adult treatment seeking substance use disorder patients with comorbid ADHD: study protocol of a randomized controlled trial 
BMC Psychiatry  2013;13:132.
Attention deficit hyperactivity disorder (ADHD) frequently co-occurs with substance use disorders (SUD). The combination of ADHD and SUD is associated with a negative prognosis of both SUD and ADHD. Pharmacological treatments of comorbid ADHD in adult patients with SUD have not been very successful. Recent studies show positive effects of cognitive behavioral therapy (CBT) in ADHD patients without SUD, but CBT has not been studied in ADHD patients with comorbid SUD.
This paper presents the protocol of a randomized controlled trial to test the efficacy of an integrated CBT protocol aimed at reducing SUD as well as ADHD symptoms in SUD patients with a comorbid diagnosis of ADHD. The experimental group receives 15 CBT sessions directed at symptom reduction of SUD as well as ADHD. The control group receives treatment as usual, i.e. 10 CBT sessions directed at symptom reduction of SUD only. The primary outcome is the level of self-reported ADHD symptoms. Secondary outcomes include measures of substance use, depression and anxiety, quality of life, health care consumption and neuropsychological functions.
This is the first randomized controlled trial to test the efficacy of an integrated CBT protocol for adult SUD patients with a comorbid diagnosis of ADHD. The rationale for the trial, the design, and the strengths and limitations of the study are discussed.
Trial registration
This trial is registered in as NCT01431235.
PMCID: PMC3659028  PMID: 23663651
ADHD; SUD; Cognitive behavioral therapy; Adult; Integrated treatment
2.  Substance-use disorders in adolescents and adults with ADHD: focus on treatment 
Neuropsychiatry  2012;2(4):301-312.
A high prevalence of comorbidity of ADHD and substance-use disorders (SUDs) has been shown in the literature. In this article, the literature for the treatment of adolescents and adults with co-occurring ADHD and SUD is examined. Findings from pharmacotherapy suggest mild improvement in ADHD without demonstrable changes in SUD unless the addiction was stabilized prior to treating the ADHD. No unique adverse effects, worsening of SUD, misuse or diversion of stimulants are reported in the included studies. Treating ADHD pharmacologically in individuals with ADHD plus SUD only has a modest impact on ADHD and SUD that is not observed in controlled trials. Limited data in adults with ADHD and brief abstinence of their SUD showed improvements in both ADHD and SUD with treatment. Further studies of cognitive behavioral therapy, sequencing of therapies and longer term treatment outcomes for groups with ADHD and active SUD are necessary.
PMCID: PMC3480177  PMID: 23105949
3.  The Swedish Version of the Ritvo Autism and Asperger Diagnostic Scale: Revised (RAADS-R). A Validation Study of a Rating Scale for Adults 
There is a paucity of diagnostic instruments for adults with autism spectrum disorder (ASD). This study evaluates the psychometric properties of the Swedish version of the Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), an 80-item self-rating scale designed to assist clinicians diagnosing ASD in adults. It was administered to 75 adults with ASD and 197 comparison cases. Also, a subset completed the Autism Spectrum Quotient (AQ). Three out of four subscales had high internal consistency. Sensitivity was 91% and specificity was 93%. The ASD subjects had significantly higher mean scores on all subscales. ASD females had higher scores than ASD males on the sensory motor subscale, a dimension not included in the AQ. RAADS-R showed promising test re-test reliability.
PMCID: PMC3217140  PMID: 21327833
Autistic disorder; Asperger syndrome; Psychiatric status rating scales; Self assessment (Psychology); Diagnostic techniques and procedures; Adult
4.  Autism and ADHD Symptoms in Patients with OCD: Are They Associated with Specific OC Symptom Dimensions or OC Symptom Severity? 
In obsessive-compulsive disorder (OCD), the relationship between autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) symptom, and obsessive-compulsive (OC) symptom dimensions and severity has scarcely been studied. Therefore, 109 adult outpatients with primary OCD were compared to 87 healthy controls on OC, ADHD and ASD symptoms. OCD patients showed increased ADHD and autism symptom frequencies, OCD + ADHD patients reporting more autism symptoms (particularly attention switching and social skills problems) than OCD − ADHD patients. Attention switching problems were most significant predictors of OC symptom dimensions (except hoarding) and of symptom severity. Hoarding was not associated with elevated autism scale scores, but with inattention. In conclusion, attention switching problems may reflect both symptom overlap and a common etiological factor underlying ASD, ADHD and OCD.
PMCID: PMC2855859  PMID: 20039111
Obsessive-compulsive disorder; Attention deficit/hyperactivity disorder; Autism
5.  High Concordance of Parent and Teacher Attention-Deficit/Hyperactivity Disorder Ratings in Medicated and Unmedicated Children with Autism Spectrum Disorders 
Parent and teacher ratings of core attention-deficit/hyperactivity disorder (ADHD) symptoms, as well as behavioral and emotional problems commonly comorbid with ADHD, were compared in children with autism spectrum disorders (ASD).
Participants were 86 children (66 boys; mean: age=9.3 years, intelligence quotient [IQ]=84) who met American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for an ASD on the Autism Diagnostic Interview–Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). Parent and teacher behavioral ratings were compared on the Conners' Parent and Teacher Rating Scales (CPRS-R; CTRS-R). The degree to which age, ASD subtype, severity of autistic symptomatology, and medication status mediated this relationship was also examined.
Significant positive correlations between parent and teacher ratings suggest that a child's core ADHD symptoms—as well as closely related externalizing symptoms—are perceived similarly by parents and teachers. With the exception of oppositional behavior, there was no significant effect of age, gender, ASD subtype, or autism severity on the relationship between parent and teacher ratings. In general, parents rated children as having more severe symptomatology than did teachers. Patterns of parent and teacher ratings were highly correlated, both for children who were receiving medication, and for children who were not.
Parents and teachers perceived core symptoms of ADHD and closely-related externalizing problems in a similar manner, but there is less agreement on ratings of internalizing problems (e.g., anxiety). The clinical implication of these findings is that both parents and teachers provide important behavioral information about children with ASD. However, when a clinician is unable to access teacher ratings (e.g., during school vacations), parent ratings can provide a reasonable estimate of the child's functioning in these domains in school. As such, parent ratings can be reliably used to make initial diagnostic and treatment decisions (e.g., medication treatment) regarding ADHD symptoms in children with ASDs.
PMCID: PMC3422050  PMID: 22849541
6.  Inhibition, flexibility, working memory and planning in autism spectrum disorders with and without comorbid ADHD-symptoms 
Recent studies have not paid a great deal of attention to comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms in autistic children even though it is well known that almost half of children with autism spectrum disorder (ASD) suffer from hyperactivity, inattention and impulsivity. The goal of this study was to evaluate and compare executive functioning (EF) profiles in children with ADHD and in children with ASD with and without comorbid ADHD.
Children aged 6 to 18 years old with ADHD (n = 20) or ASD (High-Functioning autism or Asperger syndrome) with (n = 20) and without (n = 20) comorbid ADHD and a typically developing group (n = 20) were compared on a battery of EF tasks comprising inhibition, flexibility, working memory and planning tasks. A MANOVA, effect sizes as well as correlations between ADHD-symptomatology and EF performance were calculated. Age- and IQ-corrected z scores were used.
There was a significant effect for the factor group (F = 1.55; dF = 42; p = .02). Post-hoc analysis revealed significant differences between the ADHD and the TD group on the inhibition task for false alarms (p = .01) and between the ADHD group, the ASD+ group (p = .03), the ASD- group (p = .02) and the TD group (p = .01) for omissions. Effect sizes showed clear deficits of ADHD children in inhibition and working memory tasks. Participants with ASD were impaired in planning and flexibility abilities. The ASD+ group showed compared to the ASD- group more problems in inhibitory performance but not in the working memory task.
Our findings replicate previous results reporting impairment of ADHD children in inhibition and working memory tasks and of ASD children in planning and flexibility abilities. The ASD + group showed similarities to the ADHD group with regard to inhibitory but not to working memory deficits. Nevertheless the heterogeneity of these and previous results shows that EF assessment is not useful for differential diagnosis between ADHD and ASD. It might be useful for evaluating strengths and weaknesses in individual children.
PMCID: PMC2276205  PMID: 18237439
7.  Applying an ESSENCE Framework to Understanding Adult Autism Spectrum Disorder and ADHD: Retrospective Parent Reports of Childhood Problems 
The Scientific World Journal  2013;2013:469594.
Diagnoses of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are increasingly being made in adulthood. However, assessments can fail to address the diverse range of problems that patients have experienced. The current study applied an early symptomatic syndromes eliciting neurodevelopmental clinical examinations (ESSENCE) framework to explore retrospectively reported childhood developmental and behavioral problems. It examined if adult ASD and ADHD patients would show problems outside those reflected in the respective diagnostic criteria, and also if these patient groups would show more extensive childhood problems than other psychiatric patients. Parents of adults with ADHD (n = 130), ASD (n = 57), coexisting ADHD and ASD (n = 38), and other psychiatric disorders (n = 56) reported on a range of childhood problems. Descriptions of the ADHD, ASD, and ADHD+ASD groups reflected greater impairment than descriptions for patients with other psychiatric disorders in most problem areas. Although differences were observed between ADHD and ASD patients in the core diagnostic areas, these syndromes also shared a number of childhood difficulties. The ESSENCE approach can assist in understanding the symptom history of adult ADHD and ASD patients and can be helpful to distinguish their childhood experiences from other psychiatric patients' experiences.
PMCID: PMC3619693  PMID: 23633937
8.  Attention deficit/hyperactivity disorder symptoms moderate cognition and behavior in children with autism spectrum disorders 
Recent estimates suggest that over 30% of children with autism spectrum disorders (ASD) meet diagnostic criteria for attention deficit/hyperactivity disorder (ADHD), and another 20% of children with ASD exhibit subthreshold clinical ADHD symptoms. Presence of ADHD symptoms in the context of ASD could have a variety of effects on cognition, autistic traits, and adaptive/maladaptive behaviors including: exacerbating core ASD impairments; adding unique impairments specific to ADHD; producing new problems unreported in ASD or ADHD; having no clear impact; or producing some combination of these scenarios. Children with ASD and co-morbid ADHD symptoms (ASD+ADHD; n=21), children with ASD without ADHD (ASD; n=28), and a typically developing control group (n=21) were included in the study; all groups were matched on age, gender-ratio, IQ, and socioeconomic status. Data were collected on verbal and spatial working memory, response inhibition, global executive control, autistic traits, adaptive functioning, and maladaptive behavior problems. In this sample, the presence of ADHD symptoms in ASD exacerbated impairments in executive control and adaptive behavior and resulted in higher autistic trait, and externalizing behavior ratings. ADHD symptoms were also associated with greater impairments on a lab measure of verbal working memory. These findings suggest that children with ASD+ADHD symptoms present with exacerbated impairments in some but not all domains of functioning relative to children with ASD, most notably in adaptive behavior and working memory. Therefore, ADHD may moderate the expression of components of the ASD cognitive and behavioral phenotype, but ASD+ADHD may not represent an etiologically distinct phenotype from ASD alone.
PMCID: PMC3012375  PMID: 19998356
9.  Identifying Loci for the Overlap Between ADHD and ASD Using a Genome-wide QTL Linkage Approach 
The genetic basis for Autism Spectrum Disorder (ASD) symptoms in children with Attention-Deficit Hyperactivity Disorder (ADHD) was addressed using a genome-wide linkage approach.
Participants of the International Multi-Center ADHD Genetics study comprising 1143 probands with ADHD and 1453 siblings were analyzed. The total and subscale scores of the Social Communication Questionnaire (SCQ) were used as quantitative traits for multipoint regression-based linkage analyses on 5407 autosomal single-nucleotide polymorphisms applying MERLIN-regress software, both without and with inclusion of ADHD symptom scores as covariates.
The analyses without ADHD symptom scores as covariates resulted in 3 suggestive linkage signals, i.e., on chromosomes 15q24, 16p13, and 18p11. Inclusion of ADHD symptom scores as covariates resulted in additional suggestive loci on chromosomes 7q36 and 12q24, whereas the LOD score of the locus on chromosome 15q decreased below the threshold for suggestive linkage. The loci on 7q, 16p, and 18p were found for the SCQ restricted & repetitive subscale, that on 15q was found for the SCQ communication subscale, and that on 12q for the SCQ total score.
Our findings suggest that QTLs identified in this study are ASD specific, although the 15q QTL potentially has pleiotropic effects for ADHD and ASD. This study confirms that genetic factors influence ASD traits along a continuum of severity, as loci potentially underlying ASD symptoms in children with ADHD were identified even though subjects with autism had been excluded from the IMAGE sample, and supports the hypothesis that differential genetic factors underlie the three ASD dimensions.
PMCID: PMC2929476  PMID: 20610137
ADHD; autism spectrum disorder; linkage; comorbidity
10.  Psychiatric Comorbidity in Children with Autism Spectrum Disorders: A Comparison with Children with ADHD 
The present study was conducted with the aim to identify comorbid psychiatric disorders in children with autism spectrum disorders (ASD) (n = 40) and to compare those comorbidity rates to those in children with attention deficit hyperactivity disorder (ADHD) (n = 40). Participants were clinically referred children aged 7–18 years. DSM-IV classifications were used for the primary diagnosis (ASD/ADHD), while comorbid psychiatric disorders were assessed using a structured diagnostic interview, the structured clinical interview for DSM-IV, childhood diagnoses (KID-SCID). Twenty-three children with ASD (57.5 %) had at least one comorbid disorder, whereas 16 children with ADHD (40.0 %) were classified as having at least one comorbid disorder. No group differences were found with respect to this comorbidity rate or for the rate of comorbid externalizing disorders (ODD and/or CD). However, children with ASD had more comorbid internalizing disorders compared to children with ADHD. More specifically, children with ASD had higher rates of anxiety disorders, but not mood disorders. No associations between comorbidity and age or between comorbidity and the intelligence quotient was found. It is important for clinicians to always be aware of, and screen for, comorbidity, and to consider treatment for these comorbid disorders. In addition, research should focus on establishing valid and reliable screening tools as well as effective treatment options for these comorbid disorders.
PMCID: PMC3602612  PMID: 23524401
ASD; ADHD; Children; Psychiatric comorbidity
11.  Specificity of Dyspraxia in Children with Autism 
Neuropsychology  2012;26(2):165-171.
To explore the specificity of impaired praxis and postural knowledge to autism by examining three samples of children, including those with autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and typically developing (TD) children.
Twenty-four children with ASD, 24 children with ADHD, and 24 TD children, ages 8–13, completed measures assessing basic motor control (the Physical and Neurological Exam for Subtle Signs; PANESS), praxis (performance of skilled gestures to command, with imitation, and tool use) and the ability to recognize correct hand postures necessary to perform these skilled gestures (the Postural Knowledge Test; PKT).
Children with ASD performed significantly worse than TD children on all three assessments. In contrast, children with ADHD performed significantly worse than TD controls on PANESS but not on the praxis examination or PKT. Furthermore, children with ASD performed significantly worse than children with ADHD on both the praxis examination and PKT, but not on the PANESS.
Whereas both children with ADHD and children with ASD show impairments in basic motor control, impairments in performance and recognition of skilled motor gestures, consistent with dyspraxia, appear to be specific to autism. The findings suggest that impaired formation of perceptual-motor action models necessary to development of skilled gestures and other goal directed behavior is specific to autism; whereas, impaired basic motor control may be a more generalized finding.
PMCID: PMC3312580  PMID: 22288405
imitation; motor learning; procedural learning; premotor cortex; inferior parietal lobe
12.  Autistic Traits in Male and Female Students and Individuals with High Functioning Autism Spectrum Disorders Measured by the Polish Version of the Autism-Spectrum Quotient 
PLoS ONE  2013;8(9):e75236.
So far no standardized screening instrument for autism spectrum disorders for adults has been developed in Poland. The main aim of the study was to explore the properties of the Polish version of the Autism-Spectrum Quotient (AQ), especially its reliability and discriminating power. The second purpose was to establish whether the pattern of sex and area of study differences in the amount of autistic traits found in other countries also exist in Poland. The groups in the study included students (n = 2819), adults with ASD (n = 60) and a non-clinical sample (n = 60) matched with the ASD group for age, sex, education and place of residence. The Polish version of AQ proved to be reliable, although - as in studies conducted in other countries - the internal consistency coefficients for subscales (with exception for social skill) were low. ASD diagnosis was the most powerful determinant of AQ scores. Sex differences in autistic traits and a relationship between autistic traits and area of study were found.
PMCID: PMC3781127  PMID: 24086474
13.  Impaired Consonant Trigrams Test (CTT) performance relates to everyday working memory difficulties in children with autism spectrum disorders 
Individuals with autism spectrum disorders (ASD) often struggle with complex tasks, such as those requiring divided attention (simultaneously completing two independent tasks) which also place high demands on working memory. Prior research shows that divided attention is impaired in adults and children with ASD, and is related to ASD and co-morbid attention deficit/hyperactivity disorder ADHD symptoms, but the impact on everyday functioning is unclear. Because ADHD symptoms are associated with poor divided attention and working memory performance in children with ASD, we also examined ADHD symptoms as moderators of divided attention performance.
We examined performance on the Consonant Trigrams Test (CTT) between high-functioning 8–13-year-olds with ASD (n=28) and typically developing controls (n=18) matched on age and IQ. In the ASD group, we also correlated performance with ADHD symptoms and behavior ratings of everyday working memory.
CTT performance in children with ASD was significantly worse than in matched controls. A significant correlation between CTT performance and everyday working memory was observed, but CTT performance was not related to co-morbid ADHD symptoms, in the ASD group.
Divided attention with high working memory demands is a relative weakness in children with high-functioning ASD, this weakness relates to everyday functioning, and it is independent from ADHD symptoms. That ADHD symptoms are not associated with divided attention performance is inconsistent with one prior investigation, which likely results from using different divided attention tasks in the two studies.
PMCID: PMC3424610  PMID: 21390918
14.  Prevalence and Correlates of Psychotropic Medication Use in Adolescents with an Autism Spectrum Disorder with and without Caregiver-Reported Attention-Deficit/Hyperactivity Disorder 
Many youths with an autism spectrum disorder (ASD) benefit from psychotropic medication treatment of co-morbid symptom patterns consistent with attention-deficit/hyperactivity disorder (ADHD). The lack of clear indications and algorithms to direct clinical practice has led to a very poor understanding of overall medication use for these youths. The present study examined the prevalence of psychotropic medication use compared across individuals with an ASD without a caregiver-reported ADHD diagnosis (ASD-only), ADHD without ASD (ADHD-only), and an ASD with co-morbid ADHD (ASD+ADHD). Correlates of medication use were also examined.
Data on psychotropic medication from the first wave of the National Longitudinal Transition Study 2, a nationally representative study of adolescents ages 13–17 in special education, were used to compare the prevalence of medication use across the three groups, overall and by class. Separate logistic regression models were constructed for each group to examine the correlates of psychotropic medication use. Poisson regression models were used to examine correlates of the number of medications.
Youths with ASD+ADHD had the highest rates of use (58.2%), followed by youths with ADHD-only (49.0%) and youths with ASD-only (34.3%). Youths with an ASD, both ASD-only and ASD+ADHD, used medications across a variety of medication classes, whereas stimulants were dominant among youths with ADHD-only. African American youths with ASD-only and with ASD+ADHD were less likely to receive medication than white youths, whereas race was not associated with medication use in the ADHD-only group.
Clearer practice parameters for ADHD have likely contributed to more consistency in treatment, whereas treatment for ASD reflects a trial and error approach based on associated symptom patterns. Additional studies examining the treatment of core and associated ASD symptoms are needed to guide pharmacologic treatment of these youths. Interventions targeting African American youths with ASD and the physicians who serve them are also warranted.
PMCID: PMC3279713  PMID: 22166171
15.  Levels of autistic traits in anorexia nervosa: a comparative psychometric study 
BMC Psychiatry  2013;13:222.
A number of characteristics associated with Autism Spectrum Disorders (ASD) are over-represented among patients with Anorexia Nervosa (AN) as well as among relatives of these patients. Yet the co-occurrence of autistic traits in AN has not been fully explored and no previous study has directly compared self-reported evaluations of cognitive and socio-affective skills in AN and ASD.
We aimed to determine the degree of overlap between AN and ASD from scores on questionnaires classically used to measure ASD impairments. Fifteen AN participants, 15 ASD participants and two groups of matched controls completed a battery of self-reports measuring: autistic traits (Autism-Spectrum Quotient), empathy (Empathy Quotient-short and Interpersonal Reactivity Index), systemizing (Systemizing Quotient-short) and alexithymia (Bermond-Vorst Alexithymia Questionnaire-B). Univariate comparisons of mean totalled scores were performed on each measure (patients vs. controls, and AN vs. ASD), and a Principal Component Analysis was used to study subject proximities in a reduced-factor space constructed from AQ, BVAQ-B and IRI subscales.
These analyses revealed similarities in a few cognitive domains (Attention Switching, Perspective Taking and Fantasy, lack of emotional introspection) and in some nonspecific affective dimensions (depression and feelings of distress), but also marked dissimilarities in social skills (the ability to communicate emotions to others, empathizing).
The AN and ASD participants reported similar needs for sameness, and similar difficulties understanding their emotions and taking the perspective of another, but contrasting abilities to feel concerned in interpersonal situations. Our mixed findings encourage further exploration of transdiagnostic similarities and associations between these disorders.
PMCID: PMC3848448  PMID: 24015680
Anorexia nervosa; Autism; Neuropsychology; Flexibility; Interpersonal functioning; Empathy; Alexithymia
16.  Children with Autism and Attention Difficulties: A Pilot Study of the Association between Sensory, Motor, and Adaptive Behaviors 
This pilot study aimed to compare sensory processing, motor skills and adaptive behaviors in children with a double diagnosis of Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) (ASD+ADHD) with children with ADHD alone and to examine the association of sensory processing and motor skills with adaptive behaviors (self-care).
Thirty children aged 5–14 years diagnosed with ASD+ADHD (n = 13) or ADHD (n = 17) were evaluated on their sensory processing and motor skills and adaptive behaviors. Analysis of covariance compared the groups on these dimensions. Correlation analyses examined the association between sensory processing and motor skills and adaptive behaviors.
Compared to children with ADHD alone, children with ASD+ADHD had poorer skills in sensory processing (p < 0.001), motor (p = 0.001) and adaptive behaviors (p < 0.001). For all children, increased autonomy in self-care was correlated with better sensory processing (p < 0.001) and motor skills (p = 0.002).
Children with ASD+ADHD have poorer sensory processing, motor and adaptive skills than those with ADHD alone. Sensory processing and motor deficits were negatively associated with autonomy in self-care. Interventions aiming to improve sensory processing and motor skills and autonomy in self-care should become important targets for these children.
PMCID: PMC3647630  PMID: 23667360
Attention Deficit Hyperactivity Disorder; Autism Spectrum Disorder; sensory processing; motor skills; adaptive behaviors; trouble d’attention avec hyperactivité; trouble du spectre autistique; traitement de l’information sensorielle; habiletés motrices; comportements adaptatifs
17.  Subjective Effects, Misuse, and Adverse Effects of Osmotic-Release Methylphenidate Treatment in Adolescent Substance Abusers with Attention-Deficit/Hyperactivity Disorder 
Psychostimulants are effective treatments for attention-deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non–substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD.
Datasets from two randomized placebo-controlled trials of OROS-MPH for treating ADHD, one conducted with 303 adolescents (13–18) with at least one non-nicotine SUD and one with 255 adult smokers (18–55), were analyzed. Outcome measures included the Massachusetts General Hospital Liking Scale, self-reported medication compliance, pill counts, and adverse events (AEs).
Euphoric effects and misuse/diversion of OROS-MPH were not significantly affected by substance use severity. The euphoric effects of OROS-MPH did not significantly differ between the adolescent and adult samples. Adults rated OROS-MPH as more effective in treating ADHD, whereas adolescents reported feeling more depressed when taking OROS-MPH. The adolescents lost more pills relative to the adults regardless of treatment condition, which suggests the importance of careful medication monitoring. Higher baseline use of alcohol and cannabis was associated with an increased risk of experiencing a treatment-related AE in OROS-MPH, but baseline use did not increase the risk of serious AEs or of any particular category of AE and the adolescents did not experience more treatment-related AEs relative to the adults.
With good monitoring, and in the context of substance abuse treatment, OROS-MPH can be safely used in adolescents with an SUD despite non-abstinence.
PMCID: PMC3243465  PMID: 22040190
18.  Autistic traits in children with ADHD index clinical and cognitive problems 
Traits of autistic spectrum disorders (ASD) occur frequently in attention deficit hyperactivity disorder (ADHD), but the significance of their presence in terms of phenotype and underlying neurobiology is not properly understood. This analysis aimed to determine whether higher levels of autistic traits, as measured by the Social Communication Questionnaire (SCQ), index a more severe presentation in a large, rigorously phenotyped sample of children with ADHD (N = 711). Regression analyses were used to examine association of SCQ scores with core ADHD features, clinical comorbidities and cognitive and developmental features, with adjustment for putative confounders. For outcomes showing association with total SCQ score, secondary analyses determined levels of differential association of the three ASD sub-domains. Results suggest that increasing ASD symptomatology within ADHD is associated with a more severe phenotype in terms of oppositional, conduct and anxiety symptoms, lower full-scale IQ, working memory deficits and general motor problems. These associations persisted after accounting for ADHD severity, suggesting that autistic symptomatology independently indexes the severity of comorbid impairments in the context of ADHD. Sub-domain scores did not show unique contributions to most outcomes, except that social deficits were independently associated with oppositional symptoms and repetitive behaviours independently predicted hyperactive-impulsive symptoms and motor problems. It would be worthwhile for clinicians to consider levels of socio-communicative and repetitive traits in those with ADHD who do not meet diagnostic criteria for ASD, as they index higher levels of phenotypic complexity, which may have implications for efficacy of interventions.
Electronic supplementary material
The online version of this article (doi:10.1007/s00787-013-0398-6) contains supplementary material, which is available to authorized users.
PMCID: PMC3899449  PMID: 23616179
ADHD; ASD; Comorbidity; Cognitive deficits; Neurodevelopment
19.  Does ADHD Predict Substance Use Disorders? A 10-year Follow-up Study of Young Adults With ADHD 
High rates of Substance Use Disorders (SUD) have been found in samples of adolescents and adults with Attention Deficit Hyperactivity Disorder (ADHD). Predictors of SUD among ADHD children who are at risk for the development of SUD remain understudied. The main aims of this study were to identify clinically meaningful characteristics of children that predicted the future development of SUD and to see whether the role of these characteristics varied by sex.
Subjects were children and adolescents with (N=268; mean age ± SD = 10.9 ± 3.2 years) and without (N=229; mean age 11.9 ± 3.3 years) DSM-III-R ADHD followed prospectively and blindly over a ten-year follow-up period onto young adult years. Subjects were assessed with structured diagnostic interviews for psychopathology and SUDs.
Over the ten-year follow-up period, ADHD was found to be a significant predictor of any SUD (Hazards Ratio, (95% Confidence Interval) = 1.47 (1.07, 2.02); p=0.01) and cigarette smoking (2.38 (1.61, 3.53); p<0.01). Within ADHD, comorbid conduct disorder (2.74 (1.66, 4.52); p<0.01) and oppositional defiant disorder (2.21 (1.40, 3.51); p<0.01) at baseline were also found to be significant predictors of SUD. We found similar results for cigarette, alcohol, and drug use disorders. There were few meaningful sex interaction effects. We did not find any clinically significant associations for any social or family environment factors nor cognitive functioning factors (all p values > 0.05).
These results indicate that ADHD is a significant risk factor for the development of SUD and cigarette smoking in both sexes.
PMCID: PMC3104208  PMID: 21621138
ADHD; substance-use disorders; longitudinal follow-up; conduct disorder
20.  Predictors of Treatment Response in Adolescents with Comorbid Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder 
Attention-Deficit/Hyperactivity Disorder (ADHD) frequently co-occurs with substance use disorder (SUD) and is associated with poor substance-use treatment outcomes. A trial evaluating osmotic-release oral system methylphenidate (OROS-MPH) for adolescents with ADHD and SUD, concurrently receiving behavioral therapy, revealed inconsistent medication effects on ADHD or SUD. Clinical care for this population would be advanced by knowledge of treatment outcome predictors. Data from the randomized placebo-controlled trial (n=299) were analyzed. Significant treatment predictors included: 1) Substance use severity, associated with poorer ADHD and SUD outcomes, 2) ADHD severity, associated with better ADHD and SUD outcomes, 3) comorbid conduct disorder, associated with poorer ADHD outcomes, and 4) court-mandated status, associated with better SUD outcomes but poorer treatment completion. An interaction effect showed that OROS-MPH improved SUD outcomes in adolescents with comorbid conduct disorder compared to placebo. While severe SUD may require more intensive psychosocial treatment, OROS-MPH may improve substance treatment outcomes in adolescents with co-morbid attention and conduct problems.
PMCID: PMC3499678  PMID: 22889694
Attention-Deficit/Hyperactivity Disorder; Substance Use Disorder; OROS-MPH; conduct disorder; Predictors of treatment response
21.  Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with Autism 
Molecular Psychiatry  2012;18(2):236-244.
Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato–thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto–striato–parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto–striato–cerebellar dysregulation in ASD.
PMCID: PMC3554878  PMID: 22290121
ADHD; ASD; attention; dorsolateral prefrontal cortex; fMRI
22.  Beyond Autism: A Baby Siblings Research Consortium Study of High-Risk Children at Three Years of Age 
First-degree relatives of persons with an autism spectrum disorder (ASD) are at increased risk for ASD-related characteristics. As little is known about the early expression of these characteristics, this study characterizes the non-ASD outcomes of 3-year-old high-risk (HR) siblings of children with ASD.
Two groups of children without ASD participated: 507 HR siblings and 324 low-risk (LR) control subjects (no known relatives with ASD). Children were enrolled at a mean age of 8 months, and outcomes were assessed at 3 years. Outcome measures were Autism Diagnostic Observation Schedule (ADOS) calibrated severity scores, and Mullen Verbal and Non-Verbal Developmental Quotients (DQ).
At 3 years, HR siblings without an ASD outcome exhibited higher mean ADOS severity scores and lower verbal and non-verbal DQs than LR controls. HR siblings were over-represented (21% HR versus 7% LR) in latent classes characterized by elevated ADOS severity and/or low to low-average DQs. The remaining HR siblings without ASD outcomes (79%) belonged to classes in which they were not differentially represented with respect to LR siblings.
Having removed a previously identified 18.7% of HR siblings with ASD outcomes from all analyses, HR siblings nevertheless exhibited higher mean levels of ASD severity and lower levels of developmental functioning than LR children. However, the latent class membership of four-fifths of the HR siblings was not significantly different from that of LR control subjects. One-fifth of HR siblings belonged to classes characterized by higher ASD severity and/or lower levels of developmental functioning. This empirically derived characterization of an early-emerging pattern of difficulties in a minority of 3-year-old HR siblings suggests the importance of developmental surveillance and early intervention for these children.
PMCID: PMC3625370  PMID: 23452686
ASD; high-risk siblings; outcome; broad autism phenotype
23.  Symptoms of ADHD in Children with High-Functioning Autism Are Related to Impaired Verbal Working Memory and Verbal Delayed Recall 
PLoS ONE  2013;8(5):e64842.
Symptoms similar to those found in Attention-Deficit/Hyperactivity Disorder (ADHD) often occur in children with Autism Spectrum Disorders (ASD). The objective of the current study was to compare verbal working memory, acquisition and delayed recall in children with High-Functioning Autism (HFA) to children with ADHD and typically developing children (TDC). Thirty-eight children with HFA, 79 with ADHD and 50 TDC (age 8–17) were assessed with a letter/number sequencing task and a verbal list-learning task. To investigate the possible influence of attention problems in children with HFA, we divided the HFA group into children with (HFA+) or without (HFA−) “attention problems” according to the Child Behaviour Checklist 6–18. The children with HFA+ displayed significant impairment compared to TDC on all three neurocognitive measures, while the children with HFA− were significantly impaired compared to TDC only on the working memory and acquisition measures. In addition, the HFA+ group scored significantly below the HFA− group and the ADHD group on the verbal working memory and delayed recall measures. The results support the proposition that children with HFA+, HFA−, and ADHD differ not only on a clinical level but also on a neurocognitive level which may have implications for treatment.
PMCID: PMC3661504  PMID: 23717667
24.  Which DSM-IV-TR criteria best differentiate high-functioning autism spectrum disorder from ADHD and anxiety disorders in older children? 
Diagnosis of autism spectrum disorder (ASD) is often delayed in high-functioning children with milder and more varied forms of ASD. The substantial overlap between ASD and other psychiatric disorders is thought to contribute to this delay. This study examined the endorsement of DSM-IV-TR diagnostic criteria for ASD based on semi-structured parent interviews across three groups of older children referred to an ASD clinic: 55 children diagnosed with high-functioning ASD, 27 children diagnosed with attention-deficit/hyperactivity disorder (ADHD), and 23 children diagnosed with anxiety disorder. Results indicate that the criteria within the domains of communication and social relatedness were largely able to discriminate the high-functioning ASD group from the ADHD and anxiety disorder groups, but criteria within the domain of restricted/repetitive/stereotyped patterns were not.
PMCID: PMC3035910  PMID: 19759063
ADHD; anxiety disorder; autism; diagnostic differentiation
25.  Examining autistic traits in children with ADHD: Does the Autism Spectrum Extend to ADHD? 
We examined to what extent increased parent reports of autistic traits in some children with Attention Deficit Hyperactivity Disorder (ADHD) are the result of ADHD-related symptoms or qualitatively similar to the core characteristics of autism spectrum disorders (ASD). Results confirm the presence of a subgroup of children with ADHD and elevated ratings of core ASD traits (ADHD+) not accounted for by ADHD or behavioral symptoms. Further, analyses revealed greater oppositional behaviors, but not ADHD severity or anxiety, in the ADHD+ subgroup compared to those with ADHD only. These results highlight the importance of specifically examining autistic traits in children with ADHD for better characterization in studies of the underlying physiopathology and treatment.
PMCID: PMC3123401  PMID: 21108041
Autism; Autism Spectrum Disorders; Attention-Deficit/Hyperactivity Disorder; Social Reciprocity; Social Responsiveness Scale; Children's Communication Checklist-2

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