The Chinese Version of the Compensatory ADHD Behaviors Scale (CABS): A Study on Reliability, Validity, and Clinical Utility.

Purpose: With the further development of attention-deficit/hyperactivity disorder (ADHD) research, more and more assessment tools related to ADHD have been used. However, there is still no measurement instrument to evaluate the compensatory behavior of ADHD in China. This study aimed to examine the reliability and validity of the Compensatory ADHD Behaviors Scale (CABS) adapted in Chinese and explore ecological characteristics in adults with ADHD using the CABS. Patients and Methods: Data were collected from a sample of 306 adults (Mage = 26.43 years, SD = 5.32; 46.08% male). The original version CABS was translated into Chinese using the forward and backward translation procedures. Participants completed the CABS and questionnaires assessing ADHD symptoms and executive function. We utilized content validity, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and criterion validity to test the validity. Internal consistency and test-retest reliability were employed to test the reliability. Analysis of variance (ANOVA) was employed to compare ADHD subgroups based on gender, ADHD subtype, comorbidities, and medication status, while controlling for demographic variables as covariates. Results: CABS exhibited good construct validity (two factors: present-oriented and future-oriented), content validity (content validity index: 0.98), internal consistency reliability (Cronbach's alpha coefficient: 0.85 to 0.87) and test-retest reliability (intraclass correlation coefficient: 0.59 to 0.88). The results of CFA showed acceptable fitness for each subscale. CABS demonstrated significant associations with inattention symptoms and plan/organizational abilities. Medicated ADHD individuals scored higher on future-oriented effectiveness subscale of CABS than non-medicated (F = 6.106, p = 0.014). Conclusion: The results indicate that the Chinese CABS exhibited good validity and reliability. It can be considered a valid tool for assessing compensatory behaviors in Chinese adults with ADHD. Further research is needed to explore the connection between medication and compensatory behavior.

Psychometric properties of the Chinese version of the Quick Delay Questionnaire (C-QDQ) and ecological characteristics of reward-delay impulsivity of adults with ADHD.

BACKGROUND: The Quick Delay Questionnaire (QDQ) is a short questionnaire designed to assess delay-related difficulties in adults. This study aimed to examine the reliability and validity of the Chinese version of the QDQ (C-QDQ) in Chinese adults, and explore the ecological characteristics of delay-related impulsivity in Chinese adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Data was collected from 302 adults, including ADHD (n = 209) and healthy controls (HCs) (n = 93). All participants completed the C-QDQ. The convergent validity, internal consistency, retest reliability and confirmatory factor analysis (CFA) of the C-QDQ were analyzed. The correlations between C-QDQ and two laboratory measures of delay-related difficulties and Barratt Impulsiveness Scale-11 (BIS-11), the comparison of C-QDQ scores between ADHD subgroups and HCs were also analyzed. RESULTS: The Cronbach's α of C-QDQ was between 0.83 and 0.89. The intraclass correlation coefficient of C-QDQ was between 0.80 and 0.83. The results of CFA of C-QDQ favoured the original two-factor model (delay aversion and delay discounting). Significant positive associations were found between C-QDQ scores and BIS-11 total score and performance on the laboratory measure of delay-related difficulties. Participants with ADHD had higher C-QDQ scores than HCs, and female ADHD reported higher scores on delay discounting subscale than male. ADHD-combined type (ADHD-C) reported higher scores on delay aversion subscale than ADHD-inattention type (ADHD-I). CONCLUSION: The C-QDQ is a valid and reliable tool to measure delay-related responses that appears to have clinical utility. It can present the delay-related impulsivity of patients with ADHD. Compared to HCs, the level of reward-delay impulsivity was higher in ADHD.

Changes in effective connectivity during the visual-motor integration tasks: a preliminary f-NIRS study.

BACKGROUND: Visual-motor integration (VMI) is an essential skill in daily life. The present study aimed to use functional near-infrared spectroscopy (fNIRS) technology to explore the effective connectivity (EC) changes among brain regions during VMI activities of varying difficulty levels. METHODS: A total of 17 healthy participants were recruited for the study. Continuous Performance Test (CPT), Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), and Beery VMI test were used to evaluate attention performance, executive function, and VMI performance. Granger causality analysis was performed for the VMI task data to obtain the EC matrix for all participants. One-way ANOVA analysis was used to identify VMI load-dependent EC values among different task difficulty levels from brain network and channel perspectives, and partial correlation analysis was used to explore the relationship between VMI load-dependent EC values and behavioral performance. RESULTS: We found that the EC values of dorsal attention network (DAN) → default mode network (DMN), DAN → ventral attention network (VAN), DAN → frontoparietal network (FPN), and DAN → somatomotor network (SMN) in the complex condition were higher than those in the simple and moderate conditions. Further channel analyses indicated that the EC values of the right superior parietal lobule (SPL) → right superior frontal gyrus (SFG), right middle occipital gyrus (MOG) → left SFG, and right MOG → right postcentral gyrus (PCG) in the complex condition were higher than those in the simple and moderate conditions. Subsequent partial correlation analysis revealed that the EC values from DAN to DMN, VAN, and SMN were positively correlated with executive function and VMI performance. Furthermore, the EC values of right MOG → left SFG and right MOG → right PCG were positively correlated with attention performance. CONCLUSIONS: The DAN is actively involved during the VMI task and thus may play a critical role in VMI processes, in which two key brain regions (right SPL, right MOG) may contribute to the EC changes in response to increasing VMI load. Meanwhile, bilateral SFG and right PCG may also be closely related to the VMI performance.

One-year follow-up of the effectiveness and mediators of cognitive behavioural therapy among adults with attention-deficit/hyperactivity disorder: secondary outcomes of a randomised controlled trial.

BACKGROUND: The long-term effectiveness of cognitive behavioural therapy (CBT) in medicated attention-deficit/hyperactivity disorder (ADHD) adults with residual symptoms needs to be verified across multiple dimensions, especially with respect to maladaptive cognitions and psychological quality of life (QoL). An exploration of the mechanisms underlying the additive benefits of CBT on QoL in clinical samples may be helpful for a better understanding of the CBT conceptual model and how CBT works in medicated ADHD. METHODS: We conducted a secondary analysis of a randomised controlled trial including 98 medicated ADHD adults with residual symptoms who were randomly allocated to the CBT combined with medication (CBT + M) group or the medication (M)-only group. Outcomes included ADHD-core symptoms (ADHD Rating Scale), depression symptoms (Self-rating Depression Scale), maladaptive cognitions (Automatic Thoughts Questionnaire and Dysfunctional Attitude Scale), and psychological QoL (World Health Organization Quality of Life-Brief Version-psychological domain). Mixed linear models (MLMs) were used to analyse the long-term effectiveness at one-year follow-up, and structural equation modeling (SEM) was performed to explore the potential mechanisms of CBT on psychological QoL. RESULTS: ADHD patients in the CBT + M group outperformed the M-only group in reduction of ADHD core symptoms (d = 0.491), depression symptoms (d = 0.570), a trend of reduction of maladaptive cognitions (d = 0.387 and 0.395, respectively), and improvement of psychological QoL (d = - 0.433). The changes in above dimensions correlated with each other (r = 0.201 ~ 0.636). The influence of CBT on QoL was mediated through the following four pathways: 1) changes in ADHD core symptoms; 2) changes in depressive symptoms; 3) changes in depressive symptoms and then maladaptive cognitions; and 4) changes firstly in depressive symptoms, maladaptive cognitions, and then ADHD core symptoms. CONCLUSIONS: The long-term effectiveness of CBT in medicated ADHD adults with residual symptoms was further confirmed. The CBT conceptual model was verified in clinical samples, which would be helpful for a deeper understanding of how CBT works for a better psychological QoL outcome. TRIAL REGISTRATION: ChiCTR1900021705 (2019-03-05).

The Clinical Manifestation, Executive Dysfunction, and Caregiver Strain in Subthreshold Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Subthreshold attention-deficit/hyperactivity disorder (ADHD) has been suggested to be a "morbid condition" which also needs medical attention. METHODS: The present study recruited 89 children with subthreshold ADHD (sADHD), 115 children with diagnosed ADHD (cADHD), and 79 healthy controls (HC) to explore the clinical manifestation, executive functions (EFs) of sADHD, and the caregiver strain. The clinical manifestation was evaluated through clinical interviews and parent-reports. Executive functions were assessed both experimentally and ecologically. Caregiver strain was measured by a parent-reported questionnaire. RESULTS: For the clinical manifestation, both sADHD and cADHD indicated impairments when compared with HC. The comorbidities and the scaled symptoms indicated that the externalizing behaviors were relatively less serious in sADHD than cADHD, whereas the internalizing behaviors between two groups were comparable. For ecological EFs, sADHD scored between cADHD and HC in inhibition and working memory. For experimental EFs, sADHD was comparable to cADHD in inhibition, shifting, and was worse than cADHD in verbal working memory. For the caregiver strain, all scores of sADHD were between that in cADHD and that in HC. CONCLUSION: Our present findings supported the suggestion of subthreshold ADHD as "morbid condition," which should be treated with caution in clinical practice, especially for the internalizing behaviors and some key components of EFs.

Polymorphism of Estrogen Receptor Genes and Its Interactions With Neurodevelopmental Genes in Attention Deficit Hyperactivity Disorder Among Chinese Han Descent.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder with significant gender differences. The sexual dimorphism of ADHD may be associated with estrogen acting through estrogen receptors (ESR). This study investigates the impact of ESR gene polymorphism and its interactions with neurodevelopmental genes on ADHD susceptibility. METHODS: The study compared genotyping data of single nucleotide polymorphisms in ESR1 and ESR2 in 1,035 ADHD cases and 962 controls. The gene-gene interactions between ESR genes and three neurodevelopmental genes (brain-derived neurotrophic factor [BDNF], synaptosomal-associated protein of 25 kDa gene [SNAP25], and cadherin-13 [CDH13]) in ADHD were investigated using generalized multifactor dimensionality reduction and verified by logistic regression analysis. RESULTS: The G allele of rs960070/ESR2 (empirical p=0.0076) and the A allele of rs8017441/ESR2 (empirical p=0.0426) were found significantly higher in ADHD cases than in the controls but not in male or female subgroups. Though no difference was found in all subjects or females, the A allele of rs9340817/ESR1 (empirical p=0.0344) was found significantly higher in ADHD cases than controls in males. We also found genetic interaction models between ESR2 gene, neurodevelopmental genes and ADHD susceptibility in males (ESR2 rs960070/BDNF rs6265/BDNF rs2049046/SNAP25 rs362987/CDH13 rs6565113) and females (ESR2 rs960070/BDNF rs6265/BDNF rs2049046) separately, though it was negative in overall subjects. CONCLUSION: The ESR gene polymorphism associates with ADHD among Chinese Han children, with interactions between ESR genes and neurodevelopmental genes potentially influencing the susceptibility of ADHD.

Bidirectional associations between maladaptive cognitions and emotional symptoms, and their mediating role on the quality of life in adults with ADHD: a mediation model.

Background/objectives: Adults with attention-deficit/hyperactivity disorder (ADHD) have more maladaptive cognitions, emotional problems and a poorer quality of life (QoL). A verification of the psychological model in clinical samples is needed for a better understanding of the mechanisms of ADHD diagnosis on QoL via maladaptive cognitions, emotional symptoms, and their interactions. Methods: 299 ADHD participants and 122 healthy controls were recruited. ADHD core symptoms, maladaptive cognitions, emotional symptoms and psychological QoL were rated. Pearson's correlation and structural equation modeling were analyzed to explore the relationship and influence of ADHD diagnosis on QoL. Results: More maladaptive cognitions, emotional symptoms, and poorer QoL were found in the ADHD group, and the dysfunctional attitudes were on par between ADHD with or without medication (p = 0.368). Moderate to strong correlations were found between emotional symptoms, maladaptive cognitions and QoL, and ADHD core symptoms presented correlations among the above scores (r = 0.157 ~ 0.416, p < 0.01) in ADHD participants. The influence of ADHD diagnosis on QoL was mediated through maladaptive cognitions, emotional symptoms, and their bidirectional interactions (p < 0.05), especially those with stable medication. Conclusion: Our study is the first to verify the psychological model in adults with ADHD in China. The findings determined the direct influence of ADHD diagnosis on QoL and the indirect influence through maladaptive cognitions, emotional symptoms, and their interactions, emphasizing the importance of interventions for emotional symptoms and maladaptive cognitions for ADHD patients both with or without medication for a better QoL outcome.

Roles of obesity in mediating the causal effect of attention-deficit/hyperactivity disorder on diabetes.

AIMS: Previous observational studies have reported potential associations among attention-deficit/hyperactivity disorder (ADHD), obesity, and diabetes (including type 1 and type 2 diabetes mellitus [T1DM/T2DM]). However, whether the association between ADHD and diabetes is mediated by obesity is unknown. METHODS: With two-sample Mendelian randomization, we analysed the causal effect of ADHD on T1DM and T2DM and six obesity-related traits [including body mass index, waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), body fat percentage and basal metabolic rate] and the causal effect of these obesity-related traits on T1DM/T2DM. Finally, with multivariable Mendelian randomization, we explored and quantified the possible mediation effects of obesity-related traits on the causal effect of ADHD on T1DM/T2DM. RESULTS: Our results showed that ADHD increased the risk of T2DM by 14% [odds ratio (OR) = 1.140, 95% confidence interval (CI) = 1.005-1.293] but with no evidence of an effect on T1DM (OR = 0.916, 95% CI = 0.735-1.141, P = 0.433.). In addition, ADHD had a 6.1% increased causal effect on high WC (OR = 1.061, 95% CI = 1.024-1.099, P = 0.001) and an 8.2% increased causal effect on high WHR (OR = 1.082, 95% CI = 1.035-1.131, P = 0.001). In addition, a causal effect of genetically predicted high WC (OR = 1.870, 95% CI = 1.594-2.192, P < 0.001) on a higher risk of T2DM was found. In further analysis, WC mediated approximately 26.75% (95% CI = 24.20%-29.30%) of the causal association between ADHD and T2DM. CONCLUSIONS: WC mediates a substantial proportion of the causal effect of ADHD on the risk of T2DM, which indicated that the risk of T2DM induced by ADHD could be indirectly reduced by controlling WC as a main risk factor.

Different executive function impairments in medication-naïve children with attention-deficit/hyperactivity disorder comorbid with oppositional defiant disorder and conduct disorder.

The impairment of executive functions (EFs) in attention-deficit/hyperactivity disorder (ADHD) might vary from one individual to another, indicating high heterogeneity. Comorbidity may contribute to this heterogeneity. Disruptive behavior disorders (DBD), including oppositional defiant disorder (ODD) and conduct disorder (CD), is the most common comorbidity in ADHD. Although many studies suggest that ADHD with CD (ADHDCD+) and ADHD with ODD (ADHDODD+) should be treated differently, little research has attempted to separate these two disorders when studying the EFs and brain imaging of ADHD with DBD (ADHDDBD+). Thus, based on our ongoing research in ADHD, we have now recruited a large sample size of medication-naïve children to obtain estimates of neurocognitive function and functional brain networks. We found no EF impairment in ADHDCD+ patients compared with healthy controls (HCs). Correlation analysis showed that more severe CD symptoms were associated with better EFs. The mediation analysis revealed that the relationship between CD symptoms and inhibition function was mediated by the functional connectivity (FC) of SMN(L) - DMN(R) in the younger group. The study suggested that ADHDCD+ and ADHDODD+ are different in their EF impairment. The comorbidity of CD may not worsen the impairments and might even improve EF performance within ADHD individuals.

Relationships between sensory integration and the core symptoms of attention-deficit/hyperactivity disorder: the mediating effect of executive function.

Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by executive function deficits and functional alterations in sensory integration. The present study aimed to investigate the relationship between ADHD core symptoms, executive function, and sensory integration in children with ADHD. A total of 228 children with ADHD were recruited for our study. The Sensory Organization Test (SOT) and Child Sensory Integration Scale (CSIS) evaluated the sensory integration ability from lab-based and scaled-based perspectives, respectively. Three core components of executive functions (inhibition, working memory, and set-shifting) were assessed using both lab-based tests and the relevant factors from the behavior rating inventory of executive function (BRIEF). Partial correlation analysis was performed to explore the correlation of sensory integration with EF and ADHD core symptoms. Based on the observed significant correlation, bootstrap analyses were further conducted to explore the potential mediating effect of EF on the relationship between sensory integration and ADHD core symptoms. ADHD symptoms and EF were significantly correlated with CSIS scores; no factors were significantly correlated with SOT performance. In detail, the vestibular-balance score was negatively correlated with both inattention and hyperactivity/impulsivity symptoms, while the hyper-sensory and proprioception scores were negatively correlated with only inattention symptoms. For the scaled-based EF, vestibular-balance was negatively correlated with inhibition and working memory, and the hyper-sensory score was negatively correlated with shift factor. No correlation was found for the lab-based EF tests. The subsequent mediation analysis found that inhibition partially mediated the relationship between vestibular balance and hyperactivity/impulsivity symptoms. Working memory completely mediated the relationship between vestibular-balance, hyper-sensory, proprioception, and inattention symptoms. These results were well validated in an independent sample. Our present findings demonstrated that the functional alteration in basic sensory integration might be associated with impairments of executive functions and then lead to the behavioral expression of ADHD. The present findings might provide a new perspective to understand the occurrence of ADHD symptoms and potential precise intervention methods.

Different functional alteration in attention-deficit/hyperactivity disorder across developmental age groups: A meta-analysis and an independent validation of resting-state functional connectivity studies.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a highly complex and heterogeneous disorder. Abnormal brain connectivity in ADHD might be influenced by developmental ages which might lead to the lacking of significant spatial convergence across studies. However, the developmental patterns and mechanisms of ADHD brain connectivity remain to be fully uncovered. METHODS: In the present study, we searched PubMed, Scopus, Web of Science, and Embase for seed-based whole-brain resting-state functional connectivity studies of ADHD published through October 12th, 2020. The seeds meeting inclusion criteria were categorized into the cortex group and subcortex group, as previous studies suggested that the cortex and subcortex have different temporal patterns of development. Activation likelihood estimation meta-analysis was performed to investigate the abnormal connectivity in different age groups (all-age group, younger: <12 years, older: ≥12 years). Moreover, significant convergence of reported foci was used as seeds for validation with our independent dataset. RESULTS: As with previous studies, scarce results were found in the all-age group. However, we found that the younger group consistently exhibited hyper-connectivity between different parts of the cortex and left middle frontal gyrus, and hypo-connectivity between different parts of the cortex and left putamen/pallidus/amygdala. Whereas, the older group (mainly for adults) showed hyper-connectivity between the cortex and right precuneus/sub-gyral/cingulate gyrus. Besides, the abnormal cortico-cortical and cortico-subcortical functional connectivity in children, and the abnormal cortico-cortical functional connectivity in adults were verified in our independent dataset. CONCLUSION: Our study emphasizes the importance of developmental age effects on the study of brain networks in ADHD. Further, we proposed that cortico-cortical and cortico-subcortical connectivity might play an important role in the pathophysiology of children with ADHD, while abnormal cortico-cortical connections were more important for adults with ADHD. This work provided a potential new insight to understand the neurodevelopmental mechanisms and possible clinical application of ADHD.

Network analysis of 18 attention-deficit/hyperactivity disorder symptoms suggests the importance of "Distracted" and "Fidget" as central symptoms: Invariance across age, gender, and subtype presentations.

The network theory of mental disorders conceptualizes psychiatric symptoms as networks of symptoms that causally interact with each other. Our present study aimed to explore the symptomatic structure in children with attention-deficit/hyperactivity disorder (ADHD) using network analyses. Symptom network based on 18 items of ADHD Rating Scale-IV was evaluated in 4,033 children and adolescents with ADHD. The importance of nodes was evaluated quantitatively by examining centrality indices, including Strength, Betweenness and Closeness, as well as Predictability and Expected Influence (EI). In addition, we compared the network structure across different subgroups, as characterized by ADHD subtypes, gender and age groups to evaluate its invariance. A three-factor-community structure was identified including inattentive, hyperactive and impulsive clusters. For the centrality indices, the nodes of "Distracted" and "Fidget" showed high closeness and betweenness, and represented a bridge linking the inattentive and hyperactive/impulsive domains. "Details" and "Fidget" were the most common endorsed symptoms in inattentive and hyperactive/impulsive domains respectively. On the contrary, the "Listen" item formed a peripheral node showing weak links with all other items within the inattentive cluster, and the "Loss" item as the least central node by all measures of centrality and with low predictability value. The network structure was relatively invariant across gender, age and ADHD subtypes/presentations. The 18 items of ADHD core symptoms appear not equivalent and interchangeable. "Distracted" and "Fidget" should be considered as central, or core, symptoms for further evaluation and intervention. The network-informed differentiation of these symptoms has the potentials to refine the phenotype and reduce heterogeneity.

Corrigendum: Genetic predisposition between COVID-19 and four mental illnesses: A bidirectional, two-sample Mendelian randomization study.

[This corrects the article DOI: 10.3389/fpsyt.2021.746276.].

Compensatory mechanism of attention-deficit/hyperactivity disorder recovery in resting state alpha rhythms.

Alpha rhythms in the human electroencephalogram (EEG), oscillating at 8-13 Hz, are located in parieto-occipital cortex and are strongest when awake people close their eyes. It has been suggested that alpha rhythms were related to attention-related functions and mental disorders (e.g., Attention-deficit/hyperactivity disorder (ADHD)). However, many studies have shown inconsistent results on the difference in alpha oscillation between ADHD and control groups. Hence it is essential to verify this difference. In this study, a dataset of EEG recording (128 channel EGI) from 87 healthy controls (HC) and 162 ADHD (141 persisters and 21 remitters) adults in a resting state with their eyes closed was used to address this question and a three-gauss model (summation of baseline and alpha components) was conducted to fit the data. To our surprise, the power of alpha components was not a significant difference among the three groups. Instead, the baseline power of remission and HC group in the alpha band is significantly stronger than that of persister groups. Our results suggest that ADHD recovery may have compensatory mechanisms and many abnormalities in EEG may be due to the influence of behavior rather than the difference in brain signals.

Emotion dysregulation in adults with ADHD: The role of cognitive reappraisal and expressive suppression.

BACKGROUND: Emotion dysregulation (ED) is a common clinical feature of attention-deficit/hyperactivity disorder (ADHD). The present study examined the role of cognitive reappraisal (CR) and expressive suppression (ES) in adults with ADHD. In addition, resting-state fMRI (rs-fMRI) data were analyzed to identify neural substrates of CR/ES-ED relationships. METHODS: A total of 309 adults with ADHD and 163 healthy controls were recruited. ED was assessed using the 'emotional control' (EC) subscale from Behavior Rating Inventory of Executive Function-Adult Version. The Emotion Regulation Questionnaire was used to measure CR and ES. The functional connectivities (FCs) with the amygdala as Region of Interest, were analyzed in a subsample to explore their association with CR, ES and EC, respectively. RESULTS: Higher EC scores (indicative of lesser emotional control), as well as lower CR and higher ES utilization were detected in adults with ADHD compared with healthy controls. CR and ES were both negatively correlated with EC in adults with ADHD. Mediation analysis detected a potential effect of ADHD diagnosis on EC via CR. In addition, a unique significant mediation effect was found between ES-related FC of the right amygdala-prefrontal cortex and ED expression in adults with ADHD, confirming the '↑ES → ↓FCs [amygR-PFC] →↓EC' relationship. LIMITATIONS: Only self-reported scales and rs-fMRI data were included in these analyses. CONCLUSIONS: Our findings provide preliminary evidence that in adults with ADHD, less frequent use of CR accounts for ED expression, while more frequent use of ES may play a unique compensatory role in emotion regulation.

The potential shared brain functional alterations between adults with ADHD and children with ADHD co-occurred with disruptive behaviors.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Many previous studies have shown that the comorbid status of disruptive behaviour disorders (DBD) was a predictor for ADHD persistence into adulthood. However, the brain mechanisms underlying such a relationship remain unclear. Thus, we aim to investigate whether the brain functional alteration in adults with ADHD could also be detected in children with ADHD co-occurring with disruptive behaviours from both quantitative and categorical dimensions. METHODS: A total of 172 children with ADHD (cADHD), 98 adults with ADHD (aADHD), 77 healthy control children (cHC) and 40 healthy control adults (aHC) were recruited. The whole-brain spontaneous fluctuations in brain activity of each participant were recorded using functional near-infrared spectroscopy (fNIRS), and the functional connectivities (FCs) were calculated. We first compared the FC differences between aADHD and aHC. Then, for the regions with significantly abnormal FCs in aADHD, we further compared these features between cADHD and cHC. In addition, the correlation between these FCs and the conduct disorder (CD)/oppositional defiant disorder (ODD) symptoms were analysed in cADHD. Moreover, to render the results readily interpretable, we compared the FC differences among ADHDCD-, subthreshold ADHDCD+ and cHC groups, and among ADHDODD-, ADHDODD+ and cHC groups. Finally, we repeated the above analysis after controlling for other comorbidities and core symptoms to diminish the potential confounding effects. RESULTS: We found that compared with aHC, aADHD showed significantly increased FCs in the VN, DMN, SMN, and DAN. The aforementioned abnormal FCs were also detected in cADHD, however, in an opposite orientation. Notably, these abnormal FCs were positively correlated with CD symptoms. Finally, the subthreshold ADHDCD+ group even exhibited a tendency of adult-like increased FCs compared with the cHC. The results held after controlling for other comorbidities and core symptoms. CONCLUSION: This study provides functional neuroimaging evidence that CD might be a risk factor for ADHD persistence into adulthood. Our work highlights the importance of differentiating ADHDCD+ from ADHD and inspiring further understanding of brain development in ADHD.

Affective-cognitive-behavioral heterogeneity of Attention-Deficit/Hyperactivity Disorder (ADHD): Emotional dysregulation as a sentinel symptom differentiating "ADHD-simplex" and "ADHD-complex" syndromes?

BACKGROUND: Current DSM and ICD classifications of Attention-Deficit/Hyperactivity Disorder (ADHD) exclude emotional dysregulation (ED) in their diagnostic criteria, despite ED symptoms frequently co-occurring in ADHD and likely sharing common neurobiological substrates. In this study, we examined whether consideration of ED symptoms could delineate more informative "ADHD+ED" subphenotypes. METHOD: 4106 children with ADHD were recruited. ED and inattentive (IA) and hyperactive/impulsive (HI) symptoms were profiled using latent class analyses (LCA). The derived latent class (LC) subphenotypes were evaluated and validated in relation to comorbidity patterns, executive functions, and functional impairments. RESULTS: Five LC subphenotypes with ED symptoms were identified: IA/HI + ED profile (LC1); HI + ED profile (LC2); IA + ED profile (LC3); IA/HI profile (LC4); and IA profile (LC5). Cross-validation of the LCA model using support vector machine analysis confirmed 83% accuracy. ED positive (ED+ve) subphenotypes were associated with higher rates of oppositional defiant disorder, mood disorders, anxiety disorders, as well as more severe autistic traits and sluggish cognitive tempo symptoms. Higher rates of ecological executive functioning impairments (BRIEF ratings) were found among ED+ve subphenotypes (though no differences were detected by laboratory-based measures). Functional impairments were also more severe among participants with ED+ve subphenotypes. LIMITATIONS: The data for our LCA were cross-sectional and based primarily on parent ratings. CONCLUSION: Our classification model has parcellated IA, HI, and ED symptoms into novel informative subphenotypes. These classifications provide preliminary evidence that ED symptoms could serve as sentinel features to identify a potential "ADHD-complex" syndrome, which demarcates a more pervasive condition of greater severity, complexity, and impairment.

Genetic Predispositions Between COVID-19 and Three Cardio-Cerebrovascular Diseases.

Aims: This study was aimed to apply a Mendelian randomization design to explore the causal association between coronavirus disease 2019 (COVID-19) and three cardio-cerebrovascular diseases, including atrial fibrillation, ischemic stroke, and coronary artery disease. Methods: Two-sample Mendelian randomization was used to determine the following: 1) the causal effect of COVID-19 on atrial fibrillation (55,114 case participants vs 482,295 control participants), coronary artery disease (34,541 case participants vs 261,984 control participants), and ischemic stroke (34,217 case participants vs 40,611 control participants), which were obtained from the European Bioinformatics Institute, and 2) the causal effect of three cardio-cerebrovascular diseases on COVID-19. The single-nucleotide polymorphisms (SNPs) of COVID-19 were selected from the summary-level genome-wide association study data of COVID-19-hg genome-wide association study (GWAS) meta-analyses (round 5) based on the COVID-19 Host Genetics Initiative for participants with European ancestry. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and Mendelian randomization (MR)-Egger approaches. Results: Genetically predicted hospitalized COVID-19 was suggestively associated with ischemic stroke, with an odds ratio (OR) of 1.049 [95% confidence interval (CI) 1.003-1.098; p = 0.037] in the COVID-19 Host Genetics Initiative GWAS. When excluding the UK Biobank (UKBB) data, our analysis revealed a similar odds ratio of 1.041 (95% CI 1.001-1.082; p = 0.044). Genetically predicted coronary artery disease was associated with critical COVID-19, with an OR of 0.860 (95% CI 0.760-0.973; p = 0.017) in the GWAS meta-analysis and an OR of 0.820 (95% CI 0.722-0.931; p = 0.002) when excluding the UKBB data, separately. Limited evidence of causal associations was observed between critical or hospitalized COVID-19 and other cardio-cerebrovascular diseases included in our study. Conclusion: Our findings provide suggestive evidence about the causal association between hospitalized COVID-19 and an increased risk of ischemic stroke. Besides, other factors potentially contribute to the risk of coronary artery disease in patients with COVID-19, but not genetics.

Efficacy of cognitive behavioural therapy in medicated adults with attention-deficit/hyperactivity disorder in multiple dimensions: a randomised controlled trial.

The study aimed to evaluate the efficacy of group cognitive behavioural therapy (CBT) in medicated adults with attention-deficit/hyperactivity disorder (ADHD) with a multidimensional evaluation and follow-up to week 36. Ninety-eight adult ADHD were randomly allocated to the CBT combined with medication (CBT + M) group or the medication (M) only group. The primary endpoint was the ADHD-Rating Scale (ADHD-RS). Secondary endpoints included emotional symptoms, self-esteem, automatic thoughts, quality of life (QoL), and executive function (EF). The outcome measures were obtained at baseline (T1), after the 12-week CBT treatment (T2), and at two follow-up time points (week 24, T3, and week 36, T4). Compared to the M-only group, the patients in the CBT + M group showed an overall significantly greater reduction from baseline in ADHD core symptoms (ADHD-RS total score at T3, and inattention subscale at T2 and T3), depression and anxiety symptoms (T2-T4), state anxiety (T2 and T3) and trait anxiety (T2), automatic thoughts questionnaire at T3, and QoL (physical domain, psychological domain, and social domain, most significant at T3 and weakened at T4). These findings further confirmed the efficacy of CBT on multiple dimensions and verified improvements in automatic thinking in adult ADHD. The superiority of the combination treatment mainly manifested in reduced inattention, emotional symptoms, and maladaptive thoughts and improved QoL. Trial registration number ChiCTR1900021705 (March-05-2019).

Genetic Predisposition Between COVID-19 and Four Mental Illnesses: A Bidirectional, Two-Sample Mendelian Randomization Study.

Background: The outbreak of 2019 coronavirus disease (COVID-19) has become a global pandemic. Although it has long been suspected that COVID-19 could contribute to the development of mental illness, and individuals with a pre-existing mental illness may have a higher risk of and poorer outcomes from COVID-19 infection, no evidence has established a causal association between them thus far. Methods: To investigate associations in support of a causal association between the severity of COVID-19 and mental illnesses, we leveraged large-scale genetic summary data from genome-wide association study (GWAS) summary datasets, including attention-deficit/hyperactivity disorder (ADHD) (n = 55,374), schizophrenia (n = 77,096), bipolar disorder (n = 51,710), and depression (n = 173,005), based on a previous observational study. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and MR-Egger approaches and multiple sensitivity analyses assessing horizontal pleiotropy and removing outliers in two different COVID-19 databases. Results: The Mendelian randomization (MR) analysis indicated that ADHD [odds ratio (OR) = 1.297; 95% confidence interval (CI), 1.029-1.634; p = 0.028] increased the risk of hospitalization due to COVID-19. A similar association was obtained in MR sensitivity analyses of the weighted median. In addition, genetically predicted COVID-19 was significantly associated with schizophrenia (OR = 1.043; 95% CI, 1.005-1.082; p = 0.027). Conclusions: Although many studies have reported a causal relationship between COVID-19 and mental illness, our study shows that this increased risk is modest. However, considering the characteristics of ADHD that might further increase the individuals' vulnerability to being infected by COVID-19, the ongoing massive worldwide exposure to COVID-19, and the high burden of schizophrenia, we believe that it is necessary to offer preventative measures to these populations and to provide more evidence in understanding the neurological impact of COVID-19.