Clinical,neuropsychological and structural convergences and divergences between Attention Deficit/Hyperactivity Disorder and Borderline Personality Disorder: A systematic review

Attention Deficit/Hyperactivity Disorder (ADHD) symptoms overlap with Borderline Personality Disorder (BPD). Since ADHD presents earlier than BPD, ADHD might be either a risk factor or a prodromal stage in the development of BPD or in the reinforcement of its symptoms. However, despite the similar phenomenological origin of the two disorders, ADHD and BPD patients often present discrete profiles. The present study reviews literature data of the clinical, neuropsychological and structural convergences and divergences of ADHD and BPD. A total of 185 studies were identified that address the association of ADHD and BPD and relate to clinical, neuropsychological and structural parameters. The total number of articles included was 45. ADHD exhibits a more outwardly expressed symptomatology, with difficulties in inhibition control and dysfunction in ventrolateral prefrontal regions. BPD presents a more mixed picture of externalizing and interrelating clinical features with emotionally conditioned cognitive disturbances and dysfunction in the orbitofrontal and dorsolateral prefrontal regions. When considering the three abovementioned parameters there is no unique clear-cut point that can differentiate the two disorders in a definitive way. Both disorders share impulsivity, emotional dysregulation, deficits in attention and decision making, brain volume reductions and connectivity impairments in prefrontal and limbic areas.     

Overlapping and Distinct Cognitive Impairments in Attention-Deficit/Hyperactivity and Autism Spectrum Disorder without Intellectual Disability

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are commonly comorbid, share genetic liability, and often exhibit overlapping cognitive impairments. Clarification of shared and distinct cognitive effects while considering comorbid symptoms across disorders has been lacking. In the current study, children ages 7–15 years assigned to three diagnostic groups:ADHD (n?=?509), ASD (n?=?97), and controls (n?=?301) completed measures spanning the cognitive domains of attention/arousal, working memory, set-shifting, inhibition, and response variability. Specific processes contributing to response variability were examined using a drift diffusion model, which separately quantified drift rate (i.e., efficiency of information processing), boundary separation (i.e., speed-accuracy trade-offs), and non-decision time. Children with ADHD and ASD were impaired on attention/arousal, processing speed, working memory, and response inhibition, but did not differ from controls on measures of delayed reward discounting, set-shifting, or interference control. Overall, impairments in the ASD group were not attributable to ADHD symptoms using either continuous symptom measures or latent categorical grouping approaches. Similarly, impairments in the ADHD group were not attributable to ASD symptoms. When specific RT parameters were considered, children with ADHD and ASD shared impairments in drift rate. However, children with ASD were uniquely characterized by a wider boundary separation. Findings suggest a combination of overlapping and unique patterns of cognitive impairment for children with ASD as compared to those with ADHD, particularly when the processes underlying reaction time measures are considered separately.     

A Systematic Review and Meta-analysis of Neuroimaging in Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) Taking Attention-Deficit Hyperactivity Disorder (ADHD) Into Account

Oppositional defiant disorder (ODD) and conduct disorder (CD) are common behavioural disorders in childhood and adolescence and are associated with brain abnormalities. This systematic review and meta-analysis investigates structural (sMRI) and functional MRI (fMRI) findings in individuals with ODD/CD with and without attention-deficit hyperactivity disorder (ADHD). Online databases were searched for controlled studies, resulting in 12 sMRI and 17 fMRI studies. In line with current models on ODD/CD, studies were classified in hot and cool executive functioning (EF). Both the meta-analytic and narrative reviews showed evidence of smaller brain structures and lower brain activity in individuals with ODD/CD in mainly hot EF-related areas: bilateral amygdala, bilateral insula, right striatum, left medial/superior frontal gyrus, and left precuneus. Evidence was present in both structural and functional studies, and irrespective of the presence of ADHD comorbidity. There is strong evidence that abnormalities in the amygdala are specific for ODD/CD as compared to ADHD, and correlational studies further support the association between abnormalities in the amygdala and ODD/CD symptoms. Besides the left precuneus, there was no evidence for abnormalities in typical cool EF related structures, such as the cerebellum and dorsolateral prefrontal cortex. Resulting areas are associated with emotion-processing, error-monitoring, problem-solving and self-control; areas associated with neurocognitive and behavioural deficits implicated in ODD/CD. Our findings confirm the involvement of hot, and to a smaller extent cool, EF associated brain areas in ODD/CD, and support an integrated model for ODD/CD (e.g. Blair, Development and Psychopathology, 17(3), 865-891, 2005).     

Zur Therapie von ADHS bei komorbiden Autismus-Spektrum-Störungen

Until recently, research on the co-occurrence of ADHD with autism spectrum disorder (ASD) has been limited by the fact that current classification systems did not allow a dual diagnosis of these two neurodevelopmental disorders. Since the DSM-5 permits a double diagnosis of ADHD plus ASD, research on their comorbidity has substantially increased. In addition to shared and distinct etiological factors, studies have revealed a high clinical impact of the combined symptomatology on affected individuals. This article provides a selective overview of evidence-based, mainly pharmacological treatment strategies in ADHD/ASD phenotypes.     

Three Dimensions of Oppositionality in Autism Spectrum Disorder

In autism spectrum disorder (ASD), symptoms of oppositional defiant disorder (ODD) are common but poorly understood. DSM-5 has adopted a tripartite model of ODD, parsing its features into ‘angry and irritable symptoms’ (AIS), ‘argumentative and defiant behavior’ (ADB) and ‘vindictiveness’. This was based on findings in non-autistic populations that each of these dimensions of oppositionality has a distinct constellation of associations with internalising and externalising psychopathology. We applied the tripartite DSM-5 ODD model to ASD to test its generalisability beyond non-ASD populations; and to elucidate the nature of ODD symptoms in ASD. Participants were 216 verbally-fluent young people (mean age?=?9.6 years, range 3.0 to 16.2 years, 82 % male) with ASD. Cross-sectional parent-and teacher-report data were analysed using bootstrap multiple regression to test the following predictions, derived from studies of non-ASD young people: (1) AIS will be the main predictor of internalising problems; (2) ADB will be the main predictor of ADHD symptoms; (3) all ODD traits will independently predict conduct disorder symptoms; (4) vindictiveness will be the main predictor of aggressive conduct problems. Our findings using both parent and teacher data were consistent with the non-ASD ODD literature. AIS were associated with internalising but not externalising problems; ADB and vindictiveness were associated with externalising but not internalising problems; and vindictiveness was the main predictor of aggression. The DSM-5 tripartite model of ODD appears to be generalisable to ASD: for people with an autistic disorder, AIS, ADB and vindictive dimensions of oppositionality have distinct associations with concurrent psychopathology, suggesting the need to assess them as separate constructs.     

Altered lateralization of dorsal language tracts in 6‐week‐old infants at risk for autism

Altered structural connectivity has been identified as a possible biomarker of autism spectrum disorder (ASD) risk in the developing brain. Core features of ASD include impaired social communication and early language delay. Thus, examining white matter tracts associated with language may lend further insight into early signs of ASD risk and the mechanisms that underlie language impairments associated with the disorder. Evidence of altered structural connectivity has previously been detected in 6‐month‐old infants at high familial risk for developing ASD. However, as language processing begins in utero, differences in structural connectivity between language regions may be present in the early infant brain shortly after birth. Here we investigated key white matter pathways of the dorsal language network in 6‐week‐old infants at high (HR) and low (LR) risk for ASD to identify atypicalities in structural connectivity that may predict altered developmental trajectories prior to overt language delays and the onset of ASD symptomatology. Compared to HR infants, LR infants showed higher fractional anisotropy (FA) in the left superior longitudinal fasciculus (SLF); in contrast, in the right SLF, HR infants showed higher FA than LR infants. Additionally, HR infants showed more rightward lateralization of the SLF. Across both groups, measures of FA and lateralization of these pathways at 6 weeks of age were related to later language development at 18 months of age as well as ASD symptomatology at 36 months of age. These findings indicate that early differences in the structure of language pathways may provide an early predictor of future language development and ASD risk.     

DEVELOPMENTAL SEX DIFFERENCES IN THE RELATION OF NEUROANATOMICAL CONNECTIVITY TO INTELLIGENCE

Recent neuroimaging research has shown sex-related differences in the relationship between brain structure and cognitive function. Anatomical studies have shown a greater reliance for cognitive function on white matter structure in adult females, and a greater reliance on gray matter structure in adult males. Functional neuroimaging studies have also shown a greater correlation between brain connectivity and cognitive function in females. However, this relationship is not present in young childhood (5 years old) but appears during the developmental period. Here sex differences in structure–function relationships and their developmental trajectory are investigated using diffusion tensor imaging (DTI) on a large cohort of over 100 normal children ages 5–18. Significant sex–X–IQ interactions on fractional anisotropy (FA), a marker for white matter organization, were seen in the left frontal lobe, in fronto-parietal areas bilaterally, and in the arcuate fasciculus bilaterally, with girls showing positive correlations of FA with IQ, and boys showing a negative correlation. Significant sex–X–IQ–X–age interactions on FA were also seen in the left frontal lobe and in fronto-parietal areas bilaterally, showing a developmental effect. These results strongly corroborate previous findings regarding sex differences in structure–function relationships regarding intelligence. Results also indicate that a naïve interpretation of “more is better” with respect to FA may not be accurate, especially in adult males.     

Sluggish cognitive tempo in children and adolescents with higher functioning autism spectrum disorders: Social impairments and internalizing symptoms

Sluggish cognitive tempo (SCT) was introduced in 1980s in the field of attention deficit hyperactivity disorder (ADHD). Studies indicate that symptoms of SCT are separate from symptoms of ADHD and independently associated with multiple domains of functioning in clinical groups and in typical development. We assessed whether similar pattern would apply to higher functioning autism spectrum disorders (ASD). Children with higher functioning ASD (N = 55; 5?15 years) were divided into the ASD+High SCT (n = 17), the ASD+Medium SCT (n = 18) and the ASD+Low SCT (n = 20) groups based on parent‐rated daydreaming and slowness on the Five to Fifteen questionnaire (FTF). The groups were compared on SCT‐related impairments found in previous studies: social skills, academic functioning, psychiatric symptoms, and processing speed. Assessment methods were the FTF, the Development and Well‐Being Assessment, and the Coding subtest of the WISC‐III. The ADHD symptoms were statistically controlled due to the overlap between SCT and ADHD. The ASD+High SCT and ASD+Medium SCT groups were significantly more likely to have the most pronounced social impairments, and the ASD+High SCT group had significantly higher rate of internalizing disorders compared to the ASD+Low SCT group. Our results suggest that children with higher functioning ASD and high or medium levels of SCT symptoms could be at higher risk for psychosocial impairments than children with higher functioning ASD with low levels of SCT symptoms. Co‐occurring ADHD symptoms do not explain the finding. Recognizing SCT symptoms in higher functioning ASD would be important to targeting preventive support.     

Neurobiology of Cocaine-Induced Organic Brain Impairment: Contributions from Functional Neuroimaging

The present review is directed at imparting the current knowledge regarding functional neuroimaging as a tool for enhancing the understanding of cerebrophysiologic and neurobehavioral consequences of stimulant abuse. Stimulants like cocaine are capable of inducing clinically significant neurocognitive impairment through direct action on the brain, and indirectly through other organs that influence cerebral physiology. Neurochemical dysregulation including profound effects on the serotonergic and dopaminergic systems have substantial physiological and neurobehavioral consequences. Brain hemorrhages, transient ischemic attacks, strokes, and seizures frequently follow cocaine use. The residual cerebropathologic consequences of cocaine are seen only in significant or pronounced brain events when structural neuroimaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are employed. However, recent research with newer functional neuroimaging techniques such as single photon emission, positron emission tomography, and quantitative electroencephalography have revealed high rates of significant alteration in brain function among cocaine users, with negative structural imaging studies. These findings are often associated with impairment on neuropsychological evaluation, also in the absence of positive findings on CT and MRI. Both cerebral metabolic and hypoperfusion anomalies are seen, especially in anterior and temporal brain regions. Observed changes can persist for months, and for some patients, may represent a permanent change in brain functioning.     

Visual search and autism symptoms: What young children search for and co‐occurring ADHD matter

Superior visual search is one of the most common findings in the autism spectrum disorder (ASD) literature. Here, we ascertain how generalizable these findings are across task and participant characteristics, in light of recent replication failures. We tested 106 3‐year‐old children at familial risk for ASD, a sample that presents high ASD and ADHD symptoms, and 25 control participants, in three multi‐target search conditions: easy exemplar search (look for cats amongst artefacts), difficult exemplar search (look for dogs amongst chairs/tables perceptually similar to dogs), and categorical search (look for animals amongst artefacts). Performance was related to dimensional measures of ASD and ADHD, in agreement with current research domain criteria (RDoC). We found that ASD symptom severity did not associate with enhanced performance in search, but did associate with poorer categorical search in particular, consistent with literature describing impairments in categorical knowledge in ASD. Furthermore, ASD and ADHD symptoms were both associated with more disorganized search paths across all conditions. Thus, ASD traits do not always convey an advantage in visual search; on the contrary, ASD traits may be associated with difficulties in search depending upon the nature of the stimuli (e.g., exemplar vs. categorical search) and the presence of co‐occurring symptoms.     

Comparing Attention to Socially-Relevant Stimuli in Autism Spectrum Disorder and Developmental Coordination Disorder

Difficulties with social interaction have been reported in both children with an autism spectrum disorder (ASD) and children with developmental coordination disorder (DCD), although these disorders have very different diagnostic characteristics. To date, assessment of social skills in a DCD population has been limited to paper-based assessment or parent report. The present study employed eye tracking methodology to examine how children attend to socially-relevant stimuli, comparing 28 children with DCD, 28 children with ASD and 26 typically-developing (TD) age-matched controls (aged 7–10). Eye movements were recorded while children viewed 30 images, half of which were classed as ‘Individual’ (one person in the scene, direct gaze) and the other half were ‘Social’ (more naturalistic scenes showing an interaction). Children with ASD spent significantly less time looking at the face/eye regions in the images than TD children, but children with DCD performed between the ASD and TD groups in this respect. Children with DCD demonstrated a reduced tendency to follow gaze, in comparison to the ASD group. Our findings confirm that social atypicalities are present in both ASD and to a lesser extent DCD, but follow a different pattern. Future research would benefit from considering the developmental nature of the observed findings and their implications for support.     

Connecting the Dots: A Review of Resting Connectivity MRI Studies in Attention-Deficit/Hyperactivity Disorder

Psychopathology is increasingly viewed from a circuit perspective in which a disorder stems not from circumscribed anomalies in discrete brain regions, but rather from impairments in distributed neural networks. This focus on neural circuitry has rendered resting state functional connectivity MRI (rs-fcMRI) an increasingly important role in the elucidation of pathophysiology including attention-deficit/hyperactivity disorder (ADHD). Unlike many other MRI techniques that focus on the properties of discrete brain regions, rs-fcMRI measures the coherence of neural activity across anatomically disparate brain regions, examining the connectivity and organization of neural circuits. In this review, we explore the methods available to investigators using rs-fcMRI techniques, including a discussion of their relative merits and limitations. We then review findings from extant rs-fcMRI studies of ADHD focusing on neural circuits implicated in the disorder, especially the default mode network, cognitive control network, and cortico-striato-thalamo-cortical loops. We conclude by suggesting future directions that may help advance subsequent rs-fcMRI research in ADHD.     

The Association between Self-Regulation and Symptoms of Autism Spectrum Disorder in Preschoolers with Externalizing Behavior Problems

The purpose of the current study was to examine the role of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in predicting deficits in self-regulation across the domains of executive functioning and emotion regulation. Parents of 40 preschoolers with externalizing behavior problems reported on children’s ADHD and ASD symptoms, and emotion regulation. Children completed a standardized executive functioning battery. Results indicated that 28% of parents and 53% of teachers rated children above the subclinical range on ASD symptoms. An interaction emerged such that higher ASD symptoms were only associated with poorer executive functioning for children with lower ADHD symptoms. However, ASD symptoms were predictive of poorer emotion regulation independent of ADHD symptoms. Findings revealed clinically significant ASD symptoms, which aided in explaining heterogeneity in self-regulation deficits.     

Anxiety Levels in Children with Autism Spectrum Disorder: A Meta-Analysis

The aim of the current study was to meta-analytically examine whether anxiety levels in children with autism spectrum disorders (ASD) are elevated. A total of 83 articles were selected from a systematic literature search and were included in the meta-analyses. Results demonstrated that children with ASD had higher anxiety levels compared to typically developing children, and this difference increased with IQ. Youth with ASD also tended to have higher anxiety levels compared to clinically referred children, and this difference increased with age. Children with ASD had higher anxiety levels compared to youth with externalizing or developmental problems, but not when compared to youth with internalizing problems. The study findings highlight the importance of more research in order to fully understand the nature and development of anxiety in children with ASD. More specifically, the results suggest that especially high-functioning adolescents with ASD may be at risk for developing anxiety disorders. Therefore, it seems important to carefully follow and monitor children with ASD transcending to adolescence.     

Processing Speed Deficits in Attention Deficit/Hyperactivity Disorder and Reading Disability

The goal of the current study was to test whether deficits in processing speed (PS) may be a shared cognitive risk factor in reading disability (RD) and Attention Deficit/Hyperactivity Disorder (ADHD), which are known to be comorbid. Literature on ADHD and RD suggests that deficits on tasks with a speeded component are seen in both of these disorders individually. The current study examined a wide range of speeded tasks in RD, ADHD, comorbid RD+ADHD, and a control group to test whether RD and ADHD have similar profiles of PS deficits, and whether these deficits are shared by the two disorders. The results suggest that a general PS deficit exists in both clinical groups compared to controls, although children with RD demonstrate greater PS deficits than children with ADHD. Two tests (underadditivity and partial correlations) were conducted to test whether these PS deficits are shared. Since we found that PS deficits were underadditive in the comorbid group and that partialling PS reduced the correlation between RD and ADHD, it appears that PS is a shared cognitive risk factor that may help explain the comorbidity of these two disorders.     

Genetics of autism spectrum disorders

Characterized by a combination of abnormalities in language, social cognition and mental flexibility, autism is not a single disorder but a neurodevelopmental syndrome commonly referred to as autism spectrum disorder (ASD). Several dozen ASD susceptibility genes have been identified in the past decade, collectively accounting for 10-20% of ASD cases. These findings, although demonstrating that ASD is etiologically heterogeneous, provide important clues about its pathophysiology. Diverse genetic and genomic approaches provide evidence converging on disruption of key biological pathways, many of which are also implicated in other allied neurodevelopmental disorders. Knowing the genes involved in ASD provides us with a crucial tool to probe both the specificity of ASD and the shared neurobiological and cognitive features across what are considered clinically distinct disorders, with the goal of linking gene to brain circuits to cognitive function.     

Behind the wheels with autism and ADHD: Brain networks involved in driving hazard detection

Driving is a cognitively challenging task, and many individuals with autism spectrum disorder (ASD) or with attention-deficit/hyperactivity disorder (ADHD) struggle to drive safely and effectively. Previous evidence suggests that core neuropsychological deficits in executive functioning (EF) and theory of mind (ToM) may impact driving in ASD and ADHD. This functional magnetic resonance imaging (fMRI) study compares the brain mechanisms underlying ToM and EF during a hazard perception driving task. Forty-six licensed drivers (14 ASD, 17 ADHD, 15 typically developing (TD)), ages 16–27 years, viewed a driving scenario in the MRI scanner and were instructed to respond to driving hazards that were either “social” (contained a human component such as a pedestrian) or “nonsocial” (physical objects such as a barrel). All groups of participants recruited regions part of the “social brain” (anterior insula, angular gyrus, right middle occipital gyrus, right cuneus/precuneus, and right inferior frontal gyrus) when processing social hazards, and regions associated with motor planning and object recognition (postcentral gyrus, precentral gyrus, and supplementary motor area) when processing nonsocial hazards. While there were no group differences in brain activation during the driving task, years licensed was predictive of greater prefrontal and temporal activation to social hazards in all participants. Findings of the current study suggest that high-functioning ASD and ADHD licensed drivers may be utilizing similar cognitive resources as TD controls for decisions related to driving-related hazard detection.     

Brain structure mediates the association between socioeconomic status and attention‐deficit/hyperactivity disorder

Low socioeconomic status (SES) is associated with greater risk for symptoms of attention‐deficit/hyperactivity disorder (ADHD). One mechanism through which SES may confer risk for ADHD is by influencing brain structure. Alterations to cortical thickness, surface area and subcortical volume have been associated with low SES and with the presence of ADHD across multiple studies. The current study examined whether cortical thickness, surface area or subcortical volume mediate the associations between SES and ADHD in youth 3–21 years old (N = 874) from the Pediatric Imaging, Neurocognition and Genetics Study. Freesurfer was used to estimate cortical thickness, surface area and subcortical volume from structural magnetic resonance imaging. Parents reported on demographics, family SES, ADHD diagnoses and the presence of child attention problems. Statistical mediation was assessed using a bootstrap resampling procedure. Controlling for parental ADHD, child age, gender, birth weight and scanner, children in low SES families were more likely to be in the ADHD group. Consistent with previous reports in this sample, low SES was associated with reduced surface area across the frontal lobe and reduced subcortical volume in the amygdala, cerebellum, hippocampus and basal ganglia. Of these regions, a significant indirect effect of SES on ADHD status through subcortical volume was observed for the left cerebellum (95% confidence interval: 0.004, 0.022), the right cerebellum (95% confidence interval: 0.006, 0.025), and the right caudate (95% confidence interval: 0.002, 0.022). Environmentally mediated changes in the cerebellum and the caudate may be neurodevelopmental mechanisms explaining elevated risk of ADHD in children in low SES families.     

Parenting Interventions for Children with Autism Spectrum and Disruptive Behavior Disorders: Opportunities for Cross-Fertilization

Empirical support exists for parent training/education (PT/PE) interventions for children with disruptive behavior disorders (DBD) and autism spectrum disorders (ASD). While the models share common roots, current approaches have largely developed independently and the research findings have been disseminated in two different literature traditions: mental health and developmental disabilities. Given that these populations often have overlapping clinical needs and are likely to receive services in similar settings, efforts to integrate the knowledge gained in the disparate literature may be beneficial. This article provides a systematic overview of the current (1995–2005) empirical research on PT/PE for children with DBD and ASD; attending to factors for cross-fertilization. Twenty-two ASD and 38 DBD studies were coded for review. Literature was compared in three main areas: (1) research methodology, (2) focus of PT/PE intervention, and (3) PT/PE procedures. There was no overlap in publication outlets between the studies for the two populations. Results indicate that there are opportunities for cross-fertilization in the areas of (1) research methodology, (2) intervention targets, and (3) format of parenting interventions. The practical implications of integrating these two highly related areas of research are identified and discussed.     

Executive function deficits in autism spectrum disorders and attention-deficit/hyperactivity disorder: examining profiles across domains and ages

Deficits in 'executive function' (EF) are characteristic of several clinical disorders, most notably Autism Spectrum Disorders (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). In this study, age- and IQ-matched groups with ASD, ADHD, or typical development (TD) were compared on a battery of EF tasks tapping three core domains: response selection/inhibition, flexibility, and planning/working memory. Relations between EF, age and everyday difficulties (rated by parents and teachers) were also examined. Both clinical groups showed significant EF impairments compared with TD peers. The ADHD group showed greater inhibitory problems on a Go-no-Go task, while the ASD group was significantly worse on response selection/monitoring in a cognitive estimates task. Age-related improvements were clearer in ASD and TD than in ADHD. At older (but not younger) ages, the ASD group outperformed the ADHD group, performing as well as the TD group on many EF measures. EF scores were related to specific aspects of communicative and social adaptation, and negatively correlated with hyperactivity in ASD and TD. Within the present groups, the overall findings suggested less severe and persistent EF deficits in ASD (including Asperger Syndrome) than in ADHD.