Remote assessment of ADHD in children and adolescents: recommendations from the European ADHD Guidelines Group following the clinical experience during the COVID-19 pandemic.

The COVID-19 pandemic led ADHD services to modify the clinical practice to reduce in-person contact as much as possible to minimise viral spread. This had far-reaching effects on day-to-day clinical practice as remote assessments were widely adopted. Despite the attenuation of the acute threat from COVID, many clinical services are retaining some remote practices. The lack of clear evidence-based guidance about the most appropriate way to conduct remote assessments meant that these changes were typically implemented in a localised, ad hoc, and un-coordinated way. Here, the European ADHD Guidelines Group (EAGG) discusses the strengths and weaknesses of remote assessment methods of children and adolescents with ADHD in a narrative review based on available data and expert opinions to highlight key recommendations for future studies and clinical practice. We conclude that going forward, despite remote working in clinical services functioning adequately during the pandemic, all required components of ADHD assessment should still be completed following national/international guidelines; however, the process may need adaptation. Social restrictions, including changes in education provision, can either mask or exacerbate features associated with ADHD and therefore assessment should carefully chart symptom profile and impairment prior to, as well as during an ongoing pandemic. While remote assessments are valuable in allowing clinical services to continue despite restrictions and may have benefits for routine care in the post-pandemic world, particular attention must be paid to those who may be at high risk but not be able to use/access remote technologies and prioritize these groups for conventional face-to-face assessments.

Structure and clinical correlates of obsessive-compulsive symptoms in a large sample of children and adolescents: a factor analytic study across five nations.

The underlying structure of obsessive-compulsive disorder (OCD) remains to be confirmed in child and adolescent populations. In this paper we report the first factor analytic study of individual OCD items from Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). OCD symptoms were assessed using the CY-BOCS symptom checklist in a sample of 854 patients with OCD (7-18 years of age) recruited from clinics in five countries. Pooled data were subjected to exploratory and confirmatory factor analysis (CFA) to identify the optimal factor structure. Various models were tested for age and gender subgroups. Also, the invariance of the solution across age and gender was tested and associations with demographic and clinical factors were explored. A three-factor model provided the best-fit solution. It consisted of the following factors: (1) harm/sexual, (2) symmetry/hoarding, (3) contamination/cleaning. The factor structure was invariant for age and gender across subgroups. Factor one was significantly correlated with anxiety, and factor two with depression and anxiety. Factor three was negatively correlated with tic disorder and attention-deficit/hyperactivity disorder (ADHD). Females had higher scores on factor two than males. The OCD symptom structure in children and adolescents is consistent across age and gender and similar to results from recent child and adolescents although hoarding may not be a separate factor. Our three-factor structure is almost identical to that seen in early studies on adults. Common mental disorders had specific patterns of associations with the different factors.

Default mode network abnormalities during state switching in attention deficit hyperactivity disorder.

BACKGROUND: Individuals with attention deficit hyperactivity disorder (ADHD) display excess levels of default mode network (DMN) activity during goal-directed tasks, which are associated with attentional disturbances and performance decrements. One hypothesis is that this is due to attenuated down-regulation of this network during rest-to-task switching. A second related hypothesis is that it may be associated with right anterior insula (rAI) dysfunction - a region thought to control the actual state-switching process. METHOD: These hypotheses were tested in the current fMRI study in which 19 adults with ADHD and 21 typically developing controls undertook a novel state-to-state switching paradigm. Advance cues signalled upcoming switches between rest and task periods and switch-related anticipatory modulation of DMN and rAI was measured. To examine whether rest-to-task switching impairments may be a specific example of a more general state regulation deficit, activity upon task-to-rest cues was also analysed. RESULTS: Against our hypotheses, we found that the process of down-regulating the DMN when preparing to switch from rest to task was unimpaired in ADHD and that there was no switch-specific deficit in rAI modulation. However, individuals with ADHD showed difficulties up-regulating the DMN when switching from task to rest. CONCLUSIONS: Rest-to-task DMN attenuation seems to be intact in adults with ADHD and thus appears unrelated to excess DMN activity observed during tasks. Instead, individuals with ADHD exhibit attenuated up-regulation of the DMN, hence suggesting disturbed re-initiation of a rest state.

The familial basis of facial emotion recognition deficits in adolescents with conduct disorder and their unaffected relatives.

BACKGROUND: There is accumulating evidence of impairments in facial emotion recognition in adolescents with conduct disorder (CD). However, the majority of studies in this area have only been able to demonstrate an association, rather than a causal link, between emotion recognition deficits and CD. To move closer towards understanding the causal pathways linking emotion recognition problems with CD, we studied emotion recognition in the unaffected first-degree relatives of CD probands, as well as those with a diagnosis of CD. METHOD: Using a family-based design, we investigated facial emotion recognition in probands with CD (n = 43), their unaffected relatives (n = 21), and healthy controls (n = 38). We used the Emotion Hexagon task, an alternative forced-choice task using morphed facial expressions depicting the six primary emotions, to assess facial emotion recognition accuracy. RESULTS: Relative to controls, the CD group showed impaired recognition of anger, fear, happiness, sadness and surprise (all p < 0.005). Similar to probands with CD, unaffected relatives showed deficits in anger and happiness recognition relative to controls (all p < 0.008), with a trend toward a deficit in fear recognition. There were no significant differences in performance between the CD probands and the unaffected relatives following correction for multiple comparisons. CONCLUSIONS: These results suggest that facial emotion recognition deficits are present in adolescents who are at increased familial risk for developing antisocial behaviour, as well as those who have already developed CD. Consequently, impaired emotion recognition appears to be a viable familial risk marker or candidate endophenotype for CD.

Overcoming barriers to effective early parenting interventions for attention-deficit hyperactivity disorder (ADHD): parent and practitioner views.

BACKGROUND: The importance of early intervention approaches for the treatment of attention-deficit hyperactivity disorder (ADHD) has been increasingly acknowledged. Parenting programmes (PPs) are recommended for use with preschool children with ADHD. However, low 'take-up' and high 'drop-out' rates compromise the effectiveness of such programmes within the community. METHODS: This qualitative study examined the views of 25 parents and 18 practitioners regarding currently available PPs for preschool children with ADHD-type problems in the UK. Semi-structured interviews were undertaken to identify both barriers and facilitators associated with programme access, programme effectiveness, and continued engagement. RESULTS AND CONCLUSIONS: Many of the themes mirrored previous accounts relating to generic PPs for disruptive behaviour problems. There were also a number of ADHD-specific themes. Enhancing parental motivation to change parenting practice and providing an intervention that addresses the parents' own needs (e.g. in relation to self-confidence, depression or parental ADHD), in addition to those of the child, were considered of particular importance. Comparisons between the views of parents and practitioners highlighted a need to increase awareness of parental psychological barriers among practitioners and for better programme advertising generally. Clinical implications and specific recommendations drawn from these findings are discussed and presented.

Mechanisms underpinning inattention and hyperactivity: neurocognitive support for ADHD dimensionality.

BACKGROUND: Taxometric and behavioral genetic studies suggest that attention deficit hyperactivity disorder (ADHD) is best modeled as a dimension rather than a category. We extended these analyses by testing for the existence of putative ADHD-related deficits in basic information processing (BIP) and inhibitory-based executive function (IB-EF) in individuals in the subclinical and full clinical ranges. Consistent with the dimensional model, we predicted that ADHD-related deficits would be expressed across the full spectrum, with the degree of deficit linearly related to the severity of the clinical presentation. METHOD: A total of 1547 children (aged 6-12 years) participated in the study. The Development and Well-Being Assessment (DAWBA) was used to classify children into groups according to levels of inattention and hyperactivity independently: (1) asymptomatic, (2) subthreshold minimal, (3) subthreshold moderate and (4) clinical ADHD. Neurocognitive performance was evaluated using a two-choice reaction time task (2C-RT) and a conflict control task (CCT). BIP and IB-EF measures were derived using a diffusion model (DM) for decomposition of reaction time (RT) and error data. RESULTS: Deficient BIP was found in subjects with minimal, moderate and full ADHD defined in terms of inattention (in both tasks) and hyperactivity/impulsivity dimensions (in the 2C-RT). The size of the deficit increased in a linear manner across increasingly severe presentations of ADHD. IB-EF was unrelated to ADHD. CONCLUSIONS: Deficits in BIP operate at subclinical and clinical levels of ADHD. The linear nature of this relationship provides support for a dimensional model of ADHD in which diagnostic thresholds are defined in terms of clinical and societal burden rather than representing discrete pathophysiological states.

Specificity of basic information processing and inhibitory control in attention deficit hyperactivity disorder.

BACKGROUND: Both inhibitory-based executive functioning (IB-EF) and basic information processing (BIP) deficits are found in clinic-referred attention deficit hyperactivity disorder (ADHD) samples. However, it remains to be determined whether: (1) such deficits occur in non-referred samples of ADHD; (2) they are specific to ADHD; (3) the co-morbidity between ADHD and oppositional defiant disorder/conduct disorder (ODD/CD) has additive or interactive effects; and (4) IB-EF deficits are primary in ADHD or are due to BIP deficits. METHOD: We assessed 704 subjects (age 6-12 years) from a non-referred sample using the Development and Well-Being Assessment (DAWBA) and classified them into five groups: typical developing controls (TDC; n = 378), Fear disorders (n = 90), Distress disorders (n = 57), ADHD (n = 100), ODD/CD (n = 40) and ADHD+ODD/CD (n = 39). We evaluated neurocognitive performance with a Two-Choice Reaction Time Task (2C-RT), a Conflict Control Task (CCT) and a Go/No-Go (GNG) task. We used a diffusion model (DM) to decompose BIP into processing efficiency, speed-accuracy trade-off and encoding/motor function along with variability parameters. RESULTS: Poorer processing efficiency was found to be specific to ADHD. Faster encoding/motor function differentiated ADHD from TDC and from fear/distress whereas a more cautious (not impulsive) response style differentiated ADHD from both TDC and ODD/CD. The co-morbidity between ADHD and ODD/CD reflected only additive effects. All ADHD-related IB-EF classical effects were fully moderated by deficits in BIP. CONCLUSIONS: Our findings challenge the IB-EF hypothesis for ADHD and underscore the importance of processing efficiency as the key specific mechanism for ADHD pathophysiology.

Suboptimal decision making and interpersonal problems in ADHD: longitudinal evidence from a laboratory task.

Over half of children with Attention-Deficit/Hyperactivity Disorder (ADHD) display interpersonal and social problems. Several lines of research suggest that suboptimal decision making, the ability to adjust choices to different risk-varying options, influences poorer choices made in social interactions. We thus measured decision making and its prediction of social problems longitudinally with the Cambridge Gambling Task in children with ADHD over four years. Children with ADHD had shown suboptimal decision making driven mainly by delay aversion at baseline and we expected this to be a stabile trait which would predict greater parent-reported social problems. From the baseline assessment (n = 70), 67% participated at the follow-up assessment, 21 from the ADHD group and 26 from the typically developing group. The mean age at the follow-up was 14.5 years old. The results confirmed our expectations that suboptimal decision making was a stabile trait in children and adolescents with ADHD. Although delay aversion did not differ from controls at follow-up it still proved to be the main longitudinal predictor for greater social problems. Our findings indicate that impulsivity in social interactions may be due to a motivational deficit in youth with ADHD.

Barriers to, and facilitators of, parenting programmes for childhood behaviour problems: a qualitative synthesis of studies of parents' and professionals' perceptions.

Disruptive behaviour problems (DBPs) during childhood exert a high burden on individuals, families and the community as a whole. Reducing this impact is a major public health priority. Early parenting interventions are recommended as valuable ways to target DBPs; however, low take-up of, and high drop-out rates from, these programmes seriously reduce their effectiveness. We present a review of published qualitative evidence relating to factors that block or facilitate access and engagement of parents with such programmes using a thematic synthesis approach. 12 papers presenting views of both parents and professionals met our inclusion and quality criteria. A large number of barriers were identified highlighting the array of challenges parents can face when considering accessing and engaging with treatment for their child with behavioural problems. Facilitating factors in this area were also identified. A series of recommendations were made with regard to raising awareness of programmes and recruiting parents, providing flexible and individually tailored support, delivering programmes through highly skilled, trained and knowledgeable therapists, and highlighting factors to consider when delivering group-based programmes. Clinical guidelines should address barriers and facilitators of engagement as well as basic efficacy of treatment approaches.

The relationship between ADHD and key cognitive phenotypes is not mediated by shared familial effects with IQ.

BACKGROUND: Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ. METHOD: Multivariate familial models were run on data from 1265 individuals aged 6-18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice-delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI). RESULTS: Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41-0.71) and IQ (rF=-0.25 to -0.49). The association between ADHD and cognitive performance was largely independent (80-87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ. CONCLUSIONS: The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.

European guidelines on managing adverse effects of medication for ADHD.

The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks.

Predictability of oppositional defiant disorder and symptom dimensions in children and adolescents with ADHD combined type.

BACKGROUND: Oppositional defiant disorder (ODD) is frequently co-occurring with attention deficit hyperactivity disorder (ADHD) in children and adolescents. Because ODD is a precursor of later conduct disorder (CD) and affective disorders, early diagnostic identification is warranted. Furthermore, the predictability of three recently confirmed ODD dimensions (ODD-irritable, ODD-headstrong and ODD-hurtful) may assist clinical decision making. METHOD: Receiver-operating characteristic (ROC) analysis was used in order to test the diagnostic accuracy of the Conners' Parent Rating Scale revised (CPRS-R) and the parent version of the Strength and Difficulties Questionnaire (PSDQ) in the prediction of ODD in a transnational sample of 1093 subjects aged 5-17 years from the International Multicentre ADHD Genetics study. In a second step, the prediction of three ODD dimensions by the same parent rating scales was assessed by backward linear regression analyses. RESULTS: ROC analyses showed adequate diagnostic accuracy of the CPRS-R and the PSDQ in predicting ODD in this ADHD sample. Furthermore, the three-dimensional structure of ODD was confirmed by confirmatory factor analysis and the CPRS-R emotional lability scale significantly predicted the ODD irritable dimension. CONCLUSIONS: The PSDQ and the CPRS-R are both suitable screening instruments in the identification of ODD. The emotional lability scale of the CPRS-R is an adequate predictor of irritability in youth referred for ADHD.

Eunethydis: a statement of the ethical principles governing the relationship between the European group for ADHD guidelines, and its members, with commercial for-profit organisations.

The Eunethydis ADHD Guidelines group set out here the ethical principles governing the relationship between the group and industry. The principles set out here are provided to ensure that this is both done and seen to be done. The impetus for these guidelines comes from within the Group and is linked to the recognition for the need for an open and transparent basis for Group-industry relations, especially in the light of the present concern that the pharmaceutical industry may be exerting a growing influence on the actions of researchers and clinicians in the ADHD field.

ADHD and DAT1: further evidence of paternal over-transmission of risk alleles and haplotype.

We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 3'-UTR VNTR. In the current investigation, we analyzed three new sample comprising of 1,248 ADHD nuclear families to examine the allelic over-transmission of DAT1 in ADHD. The IMAGE sample, the largest of the three-replication samples, provides strong support for a parent of origin effect for allele 6 and the 10 repeat allele (intron 8 and 3'-UTR VNTR, respectively) of DAT1. In addition, a similar pattern of over-transmission of paternal risk haplotypes (constructed from the above alleles) was also observed. Some support is also derived from the two smaller samples although neither is independently significant. Although the mechanism driving the paternal over-transmission of the DAT risk alleles is not known, these finding provide further support for this phenomenon.

A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16.

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.

Cognitive control in adolescents with neurofibromatosis type 1.

Neurofibromatosis Type 1 (NF1) is a genetic disorder characterized by partial loss of growth control that affects the central nervous system. NF1 has been consistently associated with cognitive dysfunction, although there is no consensus on the cognitive profile in NF1 or on brain-cognition relationships. To clarify the pattern of cognitive dysfunction, performance of 16 NF1 patients and 16 age- and sex-matched controls (mean age = 14.5 years, SD = 1.3) was compared on computerized tasks measuring perception, executive functioning (inhibitory control, cognitive flexibility, and working memory), and motor control. A further aim of this study was to contrast performance on tasks or task parts requiring varying levels of cognitive control to find out whether this could explain potential difficulties experienced by this population in different cognitive domains or at different stages of information processing. Repeated measures analyses of variance showed that group differences, indicating poorer performance of NF1 patients, varied as a function of the level of cognitive control required. Evidence was also found for more basic motor skill problems in NF1 patients. Furthermore, NF1 patients were generally slower than controls. Results are discussed in the context of what is known about brain-cognition relationships in NF1.

A psychophysiological investigation of the interplay between orienting and executive control during stimulus conflict: A heart rate variability study.

BACKGROUND: It has been hypothesized that resting state cardiac vagal activity (CVA) - an indicator of parasympathetic nervous system activity - is a specific psychophysiological marker of executive control function. Here, we propose an alternative hypothesis - that CVA is associated with early stage attention orientation, promoting the flexible uptake of new information, on which the later operation of such executive control functions depends. We therefore predicted that CVA would predict the interaction between orienting and executive control. This was tested using the revised version of the Attention Network Test (ANT-R) that was developed to distinguish between orienting and executive attention during a stimulus conflict task. METHODS: Healthy adults (N = 48) performed the ANT-R and their resting CVA was measured over a 5 min period using ECG recordings. RESULTS: Multiple regression analyses indicated that, when other factors were controlled for, CVA was more strongly associated with the interaction between the orienting and executive control terms than with either factor individually. CONCLUSION: Higher levels of CVA are specifically implicated in the modulation of executive control by intrinsic orientation operating at early stages of conflict detection. These initial findings of higher CVA on orienting attention in conflict detection need to be replicated in larger samples.

Inattentive/overactive children with histories of profound institutional deprivation compared with standard ADHD cases: a brief report.

BACKGROUND: The Inattention/Overactivity/Impulsiveness (I/OA) behavioural cluster diagnostic of ADHD is recognized as a characteristic outcome of early institutional care. METHODS: We compared the symptom and neuropsychological profiles of children with a history of I/OA and early severe deprivation (D-I/OA: n=13) with standard clinical ADHD cases (S-ADHD; N=20) and children who had experienced deprivation but were not pervasively I/OA (ERA-controls; n=22). The mean age of testing was around 13 years. D-I/OA and ERA-controls were selected from the English and Romanian Adoptees (ERA) study and had spent their early lives in the extremely depriving Romanian institutions of the Ceausescu regime and were later adopted into UK families. RESULTS: ADHD symptoms for male D-I/OA and S-ADHD cases showed marked similarities across symptom domains. In contrast, girls with D-I/OA were more similar to ERA controls than to ADHD cases. Longitudinal data suggested that this was due to a remission of symptoms in D-I/OA girls. Neuropsychological profiles of males and females with D-I/OA, however, were similar: both were more impaired than S-ADHD and ERA controls. DISCUSSION: Children with D-I/OA were more neuropsychologically impaired than S-ADHD despite the fact that only boys showed a persistent pattern of ADHD symptoms. These results need replication in a larger sample with groups matched for gender.

Association of ADHD with genetic variants in the 5'-region of the dopamine transporter gene: evidence for allelic heterogeneity.

Multiple studies have reported an association between attention deficit hyperactivity disorder (ADHD) and the 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region (3'UTR) of the dopamine transporter gene (DAT1). Yet, recent meta-analyses of available data find little or no evidence for this association; although there is strong evidence for heterogeneity between datasets. This pattern of findings could arise for several reasons including the presence of relatively rare risk alleles on common haplotype backgrounds or the functional interaction of two or more loci within the gene. We previously described the importance of a specific haplotype at the 3' end of DAT1, as well as the identification of associated single nucleotide polymorphisms (SNPs) within or close to 5' regulatory sequences. In this study we replicate the association of SNPs at the 5' end of the gene and identify a specific risk haplotype spanning the 5' and 3' markers. These findings indicate the presence of at least two loci associated with ADHD within the DAT1 gene and suggest that either additive or interaction effects of these two loci on the risk for ADHD. Overall these data provide further evidence that genetic variants of the dopamine transporter gene confer an increased risk for ADHD.

Replication of a rare protective allele in the noradrenaline transporter gene and ADHD.

Replication is a key to resolving whether a reported genetic association represents a false positive finding or an actual genetic risk factor. In a previous study screening 51 candidate genes for association with ADHD in a multi-centre European sample (the IMAGE project), two single nucleotide polymorphisms (SNPs) within the norepinephrine transporter (SLC6A2) gene were found to be associated with attention deficit hyperactivity disorder (ADHD). The same SNP alleles were also reported to be associated with ADHD in a separate study from the Massachusetts General Hospital in the US. Using two independent samples of ADHD DSM-IV combined subtype trios we attempted to replicate the reported associations with SNPs rs11568324 and rs3785143 in SLC6A2. Significant association of the two markers was not observed in the two independent replication samples. However, across all four datasets the overall evidence of association with ADHD was significant (for SNP rs11568324 P = 0.0001; average odds ratio = 0.33; for SNP rs3785143 P = 0.008; average odds ratio = 1.3). The data were consistent for rs11568324, suggesting the existence of a rare allele conferring protection for ADHD within the SLC6A2 gene. Further investigations should focus on identifying the mechanisms underlying the protective effect.