Structural anomalies in the frontal lobe and basal ganglia have been reported in patients with attention-deficit/hyperactivity disorder (ADHD). However, these findings have been not always consistent because of ADHD diversity. This study aimed to identify ADHD subtypes based on cognitive function and find their distinct brain structural characteristics.

Using the data of 656 children with ADHD from the Adolescent Brain Cognitive Development (ABCD) Study, we applied unsupervised machine learning to identify ADHD subtypes using the National Institutes of Health Toolbox Tasks. Moreover, we compared the regional brain volumes between each ADHD subtype and 6601 children without ADHD (non-ADHD).

Hierarchical cluster analysis automatically classified ADHD into three distinct subtypes: ADHD-A (n = 212, characterized by high-order cognitive ability), ADHD-B (n = 190, characterized by low cognitive control, processing speed, and episodic memory), and ADHD-C (n = 254, characterized by strikingly low cognitive control, working memory, episodic memory, and language ability). Structural analyses revealed that the ADHD-C type had significantly smaller volumes of the left inferior temporal gyrus and right lateral orbitofrontal cortex than the non-ADHD group, and the right lateral orbitofrontal cortex volume was positively correlated with language performance in the ADHD-C type. However, the volumes of the ADHD-A and ADHD-B types were not significantly different from those of the non-ADHD group.

These results indicate the presence of anomalies in the lateral orbitofrontal cortex associated with language deficits in the ADHD-C type. Subtype specificity may explain previous inconsistencies in brain structural anomalies reported in ADHD.

Attention-deficit hyperactivity disorder (ADHD) is often comorbid with other medical conditions in adult patients. However, ADHD is extremely underdiagnosed in adults and little is known about the medical comorbidities in undiagnosed adult individuals with high ADHD liability. In this study we investigated associations between ADHD genetic liability and electronic health record (EHR)-based ICD-10 diagnoses across all diagnostic categories, in individuals without ADHD diagnosis history.

We used data from the Estonian Biobank cohort (N = 111 261) and generated polygenic risk scores (PRS) for ADHD (PRSADHD) based on the ADHD genome-wide association study. We performed a phenome-wide association study (PheWAS) to test for associations between standardized PRSADHD and 1515 EHR-based ICD-10 diagnoses in the full and sex-stratified sample. We compared the observed significant ICD-10 associations to associations with (1) ADHD diagnosis and (2) questionnaire-based high ADHD risk analyses.

After Bonferroni correction (p = 3.3 × 10−5) we identified 80 medical conditions associated with PRSADHD. The strongest evidence was seen with chronic obstructive pulmonary disease (OR 1.15, CI 1.11–1.18), obesity (OR 1.13, CI 1.11–1.15), and type 2 diabetes (OR 1.11, CI 1.09–1.14). Sex-stratified analysis generally showed similar associations in males and females. Out of all identified associations, 40% and 78% were also observed using ADHD diagnosis or questionnaire-based ADHD, respectively, as the predictor.

Overall our findings indicate that ADHD genetic liability is associated with an increased risk of a substantial number of medical conditions in undiagnosed individuals. These results highlight the need for timely detection and improved management of ADHD symptoms in adults.

The current investigation assessed a) the performance of the FOCUS ADHD mobile health application (App) in increasing pharmacological treatment adherence and improving patients’ knowledge of attention-deficit/hyperactivity disorder (ADHD) and b) the impact of implementing a financial incentive for using the App (i.e., a discount on medication).

In a randomized, blind, parallel-group clinical trial, 73 adults diagnosed with ADHD were allocated into three groups for 3 months: a) Pharmacological treatment as usual (TAU); b) TAU and the App (App Group); and c) TAU and the App + a commercial discount on the purchase of medication prescribed for ADHD treatment (App + Discount Group).

There was no significant difference in mean treatment adherence between groups, assessed as a medication possession ratio (MPR). However, the App + Discount Group exhibited greater medication intake registrations compared with the App Group during the initial phase of the trial. The financial discount also produced a 100% App adoption rate. App use did not increase ADHD knowledge, though knowledge scores were high at baseline. The usability and quality of the App were rated favorably.

The FOCUS ADHD App achieved a high adoption rate and positive evaluations by users. Use of the App did not increase adherence to treatment as measured by MPR, but, for App users, the addition of a financial incentive to use the App produced an increase in treatment adherence in terms of medication intake registrations. The present results offer encouraging data for combining incentives with mobile digital health solutions to positively impact treatment adherence in ADHD.

The aims were to investigate patterns of labour market integration following an adult diagnosis of attention-deficit/hyperactivity disorder (ADHD) and its relation to sociodemographic factors and comorbid disorders.

Multiple Swedish nationwide registers were used to identify 8045 individuals, aged 20–29, with an incident diagnosis of ADHD 2006–2011. Labour market integration was conceptualized according to the core-peripheral model as a continuum from a strong (core) to a weak (peripheral) connection to the labour market. Sequence analyses categorized clusters of labour market integration, from 1 year before to 5 years after their ADHD diagnosis for individuals diagnosed with ADHD and a matched control group without ADHD. Multinomial logistic regression computed odds ratios (ORs) with 95% confidence intervals (CIs) between sociodemographic factors and comorbid disorders and the identified clusters.

About one-fourth of the young adults diagnosed with ADHD belonged to clusters characterized by a transition to a mainly peripheral labour market position, which was approximately four-times higher compared to controls without ADHD. Foremost, those living in small cities/villages (OR 1.9; CI 1.5–2.2), those having comorbid autism-spectrum disorder (OR 13.7; CI 6.8–27.5) or schizophrenia/psychoses (OR 7.8; CI 3.8–15.9) were associated with a transition towards a peripheral labour market position throughout the study period. Those with a high educational level (OR 0.1; CI 0.1–0.1), and men (OR 0.7; CI 0.6–0.8) were less likely to have a peripheral labour market position.

Young adults diagnosed with ADHD are four-times more likely to be in the peripheral labour market position compared to those without ADHD. To increase labour market participation, special attention is warranted to those with low educational level, those living outside big cities and those with comorbid mental disorders.

Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous neurodevelopmental disorder defined by characteristic behavioral and cognitive features. Abnormal brain dynamic functional connectivity (dFC) has been associated with the disorder. The full spectrum of ADHD-related variation of brain dynamics and its association with behavioral and cognitive features remain to be established.

We sought to identify patterns of brain dynamics linked to specific behavioral and cognitive dimensions using sparse canonical correlation analysis across a cohort of children with and without ADHD (122 children in total, 63 with ADHD). Then, using mediation analysis, we tested the hypothesis that cognitive deficits mediate the relationship between brain dynamics and ADHD-associated behaviors.

We identified four distinct patterns of dFC, each corresponding to a specific dimension of behavioral or cognitive function (r = 0.811–0.879). Specifically, the inattention/hyperactivity dimension was positively associated with dFC within the default mode network (DMN) and negatively associated with dFC between DMN and the sensorimotor network (SMN); the somatization dimension was positively associated with dFC within DMN and SMN; the inhibition and flexibility dimension and fluency and memory dimensions were both positively associated with dFC within DMN and between DMN and SMN, and negatively associated with dFC between DMN and the fronto-parietal network. Furthermore, we observed that cognitive functions of inhibition and flexibility mediated the relationship between brain dynamics and behavioral manifestations of inattention and hyperactivity.

These findings document the importance of distinct patterns of dynamic functional brain activity for different cardinal behavioral and cognitive features related to ADHD.

Neurofeedback regimes in the treatment of adult ADHD are commonly EEG-based and have several shortcomings, including a weak signal-to-noise ratio, low transfer rates from laboratory to everyday environments and ambiguous evidence in respect to adequate brain signals of interest.

To investigate, if an eyetracking-based real-time feedback in a virtual environment can enhance attentional performance, as measured by behavioral, EEG and eyetracking parameters.

Overall, n=18 adult patients with ADHD and n=18 healthy controls (HC) performed a continuous performance task (CPT) in a virtual seminar room, while distracting virtual events occurred. In case the participant’s gaze drifted away from the task an automated audiovisual feedback indicated the participant to refocus on the task. Three 20-minutes blocks were presented in counter-balanced order, that differed in respect to whether real feedback, sham feedback or no feedback was additionally provided.

Mixed ANOVAs with within-subject factors ‘Condition’ (real feedback, sham feedback, no feedback) and ‘Phase’ (distractor phases vs. non-distractor phases) and a between-factor ‘Group’ (ADHD patients vs. HC) revealed better task performances in HC than ADHD patients in respect to omission errors (p = .023), mean reaction times (p = .042) and reaction time variabilities (p = .007; cf. Figure 1). Moreover, omission errors turned to be higher during distractor-present than distractor-absent trials (p = .007), especially in ADHD.

Figure 1.

CPT results. DP=distractor-phases, NDP=non-distractor-phases

While the virtual CPT turns out to discriminate well between patients with ADHD and HC, the behavioral results do not indicate an attentional performance enhancement based on the gaze-dependent feedback.

No significant relationships.

Attention-Deficit/Hyperactivity Disorder (ADHD) runs in families; however, there are mixed results on the interaction effects of parent’s and child’s psychopathology on parenting qualities. Cognitive/schema therapy is a promising treatment approach for adult ADHD; we know little about the effect of cognitive factors on parenting, however.

We aimed to fill this gap by exploring the role of dysfunctional schema modes in the associations between adult ADHD symptoms, child’s externalizing symptoms, and perceived parental competence in a dimensional approach.

A community sample of parents (N=100, mean age=38.25 years, SD=5.73) filled out online questionnaires assessing ADHD symptoms (Adult ADHD Self-Report Scale), dysfunctional schema modes (Schema Mode Inventory), perceived parental competence (Parental Sense of Competence Scale), and child’s psychopathology (Strength and Difficulties Questionnaire).

In a multivariate model, higher levels of parental ADHD symptoms were related to higher levels of dysfunctional schema modes. However, neither the child’s externalizing symptoms nor the interaction term of parent’s symptoms by the child’s symptoms had any effect on dysfunctional schema modes. Furthermore, the child’s externalizing symptoms had a direct negative association with parental self-efficacy beliefs, whereas the relationship between adult ADHD symptoms and parental self-efficacy was mediated by the detached and overcompensating dysfunctional schema modes.

Our results suggest that the activation of dysfunctional schema modes is related to the parent’s but not the child’s psychopathology. The activation of dysfunctional schema modes may play an important role in the self-efficacy beliefs of parents with ADHD. Targeting that cognitive factors may enhance the effect of behavioral parent training programs.

This research was supported by National Research, Development, and Innovation Office (NKFIH) OTKA-PD-134849 grant.

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition in which children suffer from inattentiveness, hyperactivity, and or impulsivity. ADHD patients frequently present comorbid psychiatric disorders: in adults, the most common are depression, substance-related disorders, anxiety, and eating disorders. Children and adolescents present conduct disorders, learning disorders, anxiety and depression. Since ADHD and its psychiatric comorbidities share similarities, a partial overlap of their pathophysiological mechanisms has been suggested. ADHD, can be treated with lisdexamfetamine (LDX), a prodrug indicated by the FDA as treatment for binge eating disorder (BED) and ADHD.

To evaluate, through a systems biology-based in silico method, the efficacy of LDX as first-line ADHD treatment to improve ADHD psychiatric comorbidities. Furthermore, we explored the molecular mechanisms behind LDX’s action.

We used the systems biology- and artificial intelligence-based Therapeutic Performance Mapping System (TPMS) technology to characterise and model ADHD comorbidities. Artificial neural networks (ANNs) algorithms were used to identify specific relationships between protein sets. Finally, we modelled the mechanisms of LDX for the most relevant comorbidities by using sampling methods and comorbidity-specific virtual patients in each case.

This study predicts a strong relationship between LDX’s targets and proteins involved in BED and depression (Fig 1). Our results could be explained not only by LDX role in neurotransmitter regulation, but also by modulation of neuroplasticity (BDNF/NTRK2, GSK3), neuroinflammation (interleukins, inflammasome), oxidative stress (NOS2, SOD), and the hypothalamic-pituitary-adrenal (HPA) axis (CRH, CRHR1).

These findings could be used in pre-clinical and clinical future investigations to assess optimal treatment for ADHD patients with psychiatric comorbidities.

JRGC: speaker for Takeda and Shire, research funding from Shire and Lumbeck, collaborations with Laboratoires Servier JQ: speaker or scientific advisor for Takeda, Janssen, Rubio. Investigation funding: Instituto de Salud Carlos III. PR, CM, TPR: full-ti

Attention-Deficit/Hyperactivity Disorder (ADHD) is characterized by impairing symptoms of inattention and/or hyperactivity/impulsivity. Although Emotional Dysregulation (ED) is not current criteria for ADHD, several clinical, imaging and genetic studies have been suggesting its inclusion. ED seems to impair social and occupational capacities, leading to poor quality life. In this regard, managing this situation is fundamental.

ED in ADHD review and its management, including pharmacological and nonpharmacological approaches.

Non-systematic review through literature using databases as Pubmed and UpToDate. Keywords used: Attention-Deficit/Hyperactivity Disorder, Emotional Dysregulation, management, pharmacotherapy.

Literature refers to ADHD drugs, such as psychostimulants and atomoxetine, as the first line managing ED. However, some studies demonstrated that ADHD drugs have lower efficacy while treating emotional symptoms, when compared to attention or hyperactivity/impulsivity symptom control. Other medications, such as antidepressants or mood stabilizers, are not considered due to low efficacy and side effects (such as irritability or suicidality behaviour worsening). Regarding non pharmacological approaches, there have been results with cognitive behavioral treatment, and management techniques for anger, frustration and communication skills.

Although the majority of studies demonstrate psychostimulants and atomoxetine role, there is an important lack of information regarding management of ADHD emotional dysregulation. It is a multifactorial condition, and, as such, non pharmacological and pharmacological management are needed to address this issue. More research is necessary, in order to improve patients’ quality of life.

No significant relationships.

Executive function (EF) deficits are often associated with Autism Spectrum Disorder (ASD), even in the absence of Attention Deficit Hyperactivity Disorder (ADHD) diagnosis. To date, no approved medication treatments exist for EF deficits associated with ASD.

To assess the efficacy of transcranial photobiomodulation (tPBM) on EF in adults with ASD.

Adults (18-59) with high-functioning (HF)-ASD received twice a week tPBM for 8 weeks in an open-label single group design. ASD and EF deficits were assessed by clinician-rated Clinical Global Impression Scale and patient-rated scales of Behavior Rating Inventory of Executive Function-Adult (BRIEF-A).

Eleven participants were enrolled. Ten participants completed the study. Nine participants who completed the study had comorbid ADHD diagnosis. All 10 participants were included in efficacy analyses of EF deficits. Statistically significant improvements in executive function deficits were found in BRIEF-A total score and in subdomains of Inhibition, Emotional Control, Planning and Organization, Organization of Materials, Behavioral Regulation, Metacognitive Index and Global Executive Control. All participants were found to have mild to moderate improvement in their ADHD symptom severity per clinician rated CGIs. Statistically significant improvements in ADHD symptoms were noted in self-rated scales. No adverse events required changes in tPBM protocol.

tPBM is a safe and feasible treatment approach that has the potential to treat core features of ASD. Further research is necessary and warranted.

This work is funded by Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder and the MGH Pediatric Psychopharmacology Council Fund.

Despite a well-established link between childhood traumatic brain injury (TBI) and elevated secondary attention-deficit/hyperactivity disorder (s-ADHD) symptomology, the neurostructural correlates of these symptoms are largely unknown. Based on the influential ‘triple-network model’ of ADHD, this prospective longitudinal investigation aimed to (i) assess the effect of childhood TBI on brain morphometry of higher-order cognitive networks proposed to play a key role in ADHD pathophysiology, including the default-mode network (DMN), salience network (SN) and central executive network (CEN); and (ii) assess the independent prognostic value of DMN, SN and CEN morphometry in predicting s-ADHD symptom severity after childhood TBI.

The study sample comprised 155 participants, including 112 children with medically confirmed mild-severe TBI ascertained from consecutive hospital admissions, and 43 typically developing (TD) children matched for age, sex and socio-economic status. High-resolution structural brain magnetic resonance imaging (MRI) sequences were acquired sub-acutely in a subset of 103 children with TBI and 34 TD children. Parents completed well-validated measures of ADHD symptom severity at 12-months post injury.

Relative to TD children and those with milder levels of TBI severity (mild, complicated mild, moderate), children with severe TBI showed altered brain morphometry within large-scale, higher-order cognitive networks, including significantly diminished grey matter volumes within the DMN, SN and CEN. When compared with the TD group, the TBI group showed significantly higher ADHD symptomatology and higher rates of clinically elevated symptoms. In multivariable models adjusted for other well-established risk factors, altered DMN morphometry independently predicted higher s-ADHD symptomatology at 12-months post-injury, whilst SN and CEN morphometry were not significant independent predictors.

Our prospective study findings suggest that neurostructural alterations within higher-order cognitive circuitry may represent a prospective risk factor for s-ADHD symptomatology at 12-months post-injury in children with TBI. High-resolution structural brain MRI has potential to provide early prognostic biomarkers that may help early identification of high-risk children with TBI who are likely to benefit from early surveillance and preventive measures to optimise long-term neuropsychiatric outcomes.

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and phonic tics. It is at least three times more common in males compared with females; however, the clinical phenomenology between sexes has not been fully examined. We aimed to contrast the clinical features between males and females with TS and chronic tic disorder.

We studied 201 consecutive patients fulfilling the diagnostic criteria for TS, persistent (or chronic) motor and vocal tic disorder and provisional tic disorder that were considered within the TS spectrum disorder. We performed blinded evaluations of video-recordings and retrospectively reviewed the clinical charts of all patients.

Age ranges between 4 and 65 years. Males represented 77.6% of patients in the cohort. Overall, no differences were observed in the frequency, distribution and complexity of tics between sexes, except for a higher frequency of attention-deficit/hyperactivity disorder (ADHD) (P = .003) among males. Patients younger than 18-years old, in addition to a higher frequency of ADHD (P = .026), males had a statistically higher frequency of complex motor tics (P = .049) and earlier age at onset (P = .072) than females in the multivariate regression analysis. However, these differences were lost in patients older than 18 years, due to increased complexity of tics in females with aging.

A sexual dimorphism was observed between patients with TS mainly before age of 18 years, suggesting an earlier onset of some types of tics and ADHD in males compared to females.