The underlying neuropsychological and neural correlates of the impaired Chinese reading skills in children with attention deficit hyperactivity disorder.

Impaired basic academic skills (e.g., word recognition) are common in children with Attention Deficit Hyperactivity Disorder (ADHD). The underlying neuropsychological and neural correlates of impaired Chinese reading skills in children with ADHD have not been substantially explored. Three hundred and two children with ADHD (all medication-naïve) and 105 healthy controls underwent the Chinese language skill assessment, and 175 also underwent fMRI scans (84 ADHD and 91 controls). Between-group and mediation analyses were applied to explore the interrelationships of the diagnosis of ADHD, cognitive dysfunction, and impaired reading skills. Five ADHD-related brain functional networks, including the default mode network (DMN) and the dorsal attention network (DAN), were built using predefined regions of interest. Voxel-based group-wise comparisons were performed. The ADHD group performed worse than the control group in word-level reading ability tests, with lower scores in Chinese character recognition (CR) and word chains (WS) (all P < 0.05). With full-scale IQ and sustained attention in the mediation model, the direct effect of ADHD status on the CR score became insignificant (P = 0.066). The underlying neural correlates for the orthographic knowledge (OT) and CR differed between the ADHD and the control group. The ADHD group tended to recruit more DMN regions to maintain their reading performance, while the control group seemed to utilize more DAN regions. Children with ADHD generally presented impaired word-level reading skills, which might be caused by impaired sustained attention and lower IQ. According to the brain functional results, we infer that ADHD children might utilize a different strategy to maintain their orthographic knowledge and character recognition performance.

Altered Intrinsic Brain Spontaneous Activities in Children With Autism Spectrum Disorder Comorbid ADHD.

OBJECTIVE: The study involved 17 children with Autism Spectrum Disorder (ASD), 21 with ADHD, 30 with both (ASD + ADHD), and 28 typically developing children (TD). METHODS: The amplitude of low-frequency fluctuations (ALFF) was measured as a regional brain function index. Intrinsic functional connectivity (iFC) was also analyzed using the region of interest (ROI) identified in ALFF analysis. Statistical analysis was done via one-way ANCOVA, Gaussian random field (GRF) theory, and post-hoc pair-wise comparisons. RESULTS: The ASD + ADHD group showed increased ALFF in the left middle frontal gyrus (MFG.L) compared to the TD group. In terms of global brain function, the ASD group displayed underconnectivity in specific regions compared to the ASD + ADHD and TD groups. CONCLUSION: The findings contribute to understanding the neural mechanisms underlying ASD + ADHD.

RBFOX1 and Working Memory: From Genome to Transcriptome Revealed Posttranscriptional Mechanism Separate From Attention-Deficit/Hyperactivity Disorder.

Background: Many psychiatric disorders share a working memory (WM) impairment phenotype, yet the genetic causes remain unclear. Here, we generated genetic profiles of WM deficits using attention-deficit/hyperactivity disorder samples and validated the results in zebrafish models. Methods: We used 2 relatively large attention-deficit/hyperactivity disorder cohorts, 799 and 776 cases, respectively. WM impairment was assessed using the Rey Complex Figure Test. First, association analyses were conducted at single-variant, gene-based, and gene-set levels. Deeper insights into the biological mechanism were gained from further functional exploration by bioinformatic analyses and zebrafish models. Results: Genomic analyses identified and replicated a locus with rs75885813 as the index single nucleotide polymorphism showing significant association with WM defects but not with attention-deficit/hyperactivity disorder. Functional feature exploration found that these single nucleotide polymorphisms may regulate the expression level of RBFOX1 through chromatin interaction. Further pathway enrichment analysis of potential associated single nucleotide polymorphisms revealed the involvement of posttranscription regulation that affects messenger RNA stability and/or alternative splicing. Zebrafish with functionally knocked down or genome-edited rbfox1 exhibited WM impairment but no hyperactivity. Transcriptome profiling of rbfox1-defective zebrafish indicated that alternative exon usages of snap25a might partially lead to reduced WM learning of larval zebrafish. Conclusions: The locus with rs75885813 in RBFOX1 was identified as associated with WM. Rbfox1 regulates synaptic and long-term potentiation-related gene snap25a to adjust WM at the posttranscriptional level.

Ocular and neural genes jointly regulate the visuospatial working memory in ADHD children.

OBJECTIVE: Working memory (WM) deficits have frequently been linked to attention deficit hyperactivity disorder (ADHD). Despite previous studies suggested its high heritability, its genetic basis, especially in ADHD, remains unclear. The current study aimed to comprehensively explore the genetic basis of visual-spatial working memory (VSWM) in ADHD using wide-ranging genetic analyses. METHODS: The current study recruited a cohort consisted of 802 ADHD individuals, all met DSM-IV ADHD diagnostic criteria. VSWM was assessed by Rey-Osterrieth complex figure test (RCFT), which is a widely used psychological test include four memory indexes: detail delayed (DD), structure delayed (SD), structure immediate (SI), detail immediate (DI). Genetic analyses were conducted at the single nucleotide polymorphism (SNP), gene, pathway, polygenic and protein network levels. Polygenic Risk Scores (PRS) were based on summary statistics of various psychiatric disorders, including ADHD, autism spectrum disorder (ASD), major depressive disorder (MDD), schizophrenia (SCZ), obsessive compulsive disorders (OCD), and substance use disorder (SUD). RESULTS: Analyses at the single-marker level did not yield significant results (5E-08). However, the potential signals with P values less than E-05 and their mapped genes suggested the regulation of VSWM involved both ocular and neural system related genes, moreover, ADHD-related genes were also involved. The gene-based analysis found RAB11FIP1, whose encoded protein modulates several neurodevelopment processes and visual system, as significantly associated with DD scores (P = 1.96E-06, Padj = 0.036). Candidate pathway enrichment analyses (N = 53) found that forebrain neuron fate commitment significantly enriched in DD (P = 4.78E-04, Padj = 0.025), and dopamine transport enriched in SD (P = 5.90E-04, Padj = 0.031). We also observed a significant negative relationship between DD scores and ADHD PRS scores (P = 0.0025, Empirical P = 0.048). CONCLUSIONS: Our results emphasized the joint contribution of ocular and neural genes in regulating VSWM. The study reveals a shared genetic basis between ADHD and VSWM, with GWAS indicating the involvement of ADHD-related genes in VSWM. Additionally, the PRS analysis identifies a significant relationship between ADHD-PRS and DD scores. Overall, our findings shed light on the genetic basis of VSWM deficits in ADHD, and may have important implications for future research and clinical practice.

Cerebral blood flow characteristics of drug-naïve attention-deficit/hyperactivity disorder with social impairment: Evidence for region-symptom specificity.

Background: Social deficits are among the most important functional impairments in attention-deficit/hyperactivity disorder (ADHD). However, the relationship between social impairment and ADHD core symptoms as well as the underlying cerebral blood flow (CBF) characteristics remain unclear. Methods: A total of 62 ADHD subjects with social deficits (ADHD + SD), 100 ADHD subjects without social deficits (ADHD-SD) and 81 age-matched typically developing controls (TDC) were enrolled. We first examined the correlation between the Social Responsiveness Scale (SRS-1) and ADHD core symptoms (inattention, hyperactivity, and impulsion) and then explored categorical and dimensional ADHD-related regional CBF by arterial spin labeling (ASL). For the categorical analysis, a voxel-based comparison of CBF maps between the ADHD + SD, ADHD-SD, and TDC groups was performed. For the dimensional analysis, the whole-brain voxel-wise correlation between CBF and ADHD symptoms (inattention, hyperactivity/impulsivity, and total scores) was evaluated in three groups. Finally, correlations between the SRS-1 and ADHD-related regional CBF were investigated. We applied Gaussian random field (GRF) for the correction of multiple comparisons in imaging results (voxel-level P < 0.01, and cluster-level P < 0.05). Results: The clinical characteristics analysis showed that social deficits positively correlated with ADHD core symptoms, especially in social communication and autistic mannerisms domains. In the categorical analysis, we found that CBF in the left middle/inferior temporal gyrus in ADHD groups was higher than TDCs and was negatively correlated with the social motivation scores. Moreover, in dimensional analysis, we found that CBF in the left middle frontal gyrus was negatively correlated with the inattention scores, SRS total scores and autistic mannerisms scores in ADHD + SD subjects. Conclusion: The present study shows that inattention, hyperactivity, and impulsivity may be responsible for the occurrence of social deficits in ADHD, with autistic traits being another significant contributing factor. Additionally, CBF in the left middle/inferior temporal gyrus and the left middle frontal gyrus might represent the corresponding physiological mechanisms underlying social deficits in ADHD.

The clinical, neuropsychological, and brain functional characteristics of the ADHD restrictive inattentive presentation.

Objectives: There is an ongoing debate about the restrictive inattentive (RI) presentation of attention deficit hyperactivity disorder (ADHD). The current study aimed to systematically investigate the clinical, neuropsychological, and brain functional characteristics of children with ADHD restrictive inattentive presentation. Methods: A clinical sample of 789 children with or without ADHD participated in the current study and finished clinical interviews, questionnaires, and neuropsychological tests. Those individuals with a diagnosis of ADHD were further divided into three subgroups according to the presentation of inattentive and/or hyperactive/impulsive symptoms, the ADHD-RI, the ADHD-I (inattentive), and the ADHD-C (combined) groups. Between-group comparisons were carried out on each clinical and neuropsychological measure using ANCOVA, with age and sex as covariates. Bonferroni corrections were applied to correct for multiple comparisons. Two hundred twenty-seven of the subjects also went through resting-state functional magnetic resonance imaging scans. Five ADHD-related brain functional networks, including the default mode network (DMN), the dorsal attention network (DAN), the ventral attention network, the executive control network, and the salience network, were built using predefined regions of interest (ROIs). Voxel-based group-wise comparisons were performed. Results: Compared with healthy controls, all ADHD groups presented more clinical problems and weaker cognitive function. Among the ADHD groups, the ADHD-C group had the most clinical problems, especially delinquent and aggressive behaviors. Regarding cognitive function, the ADHD-RI group displayed the most impaired sustained attention, and the ADHD-C group had the worst response inhibition function. In terms of brain functional connectivity (FC), reduced FC in the DMN was identified in the ADHD-C and the ADHD-I groups but not the ADHD-RI group, compared to the healthy controls. Subjects with ADHD-I also presented decreased FC in the DAN in contrast to the control group. The ADHD-RI displayed marginally significantly lower FC in the salience network compared to the ADHD-I and the control groups. Conclusion: The ADHD-RI group is distinguishable from the ADHD-I and the ADHD-C groups. It is characterized by fewer externalizing behaviors, worse sustained attention, and better response inhibition function. The absence of abnormally high hyperactive/impulsive symptoms in ADHD-RI might be related to less impaired brain function in DMN, but potentially more impairment in the salience network.

The shared white matter developmental trajectory anomalies of attention-deficit/hyperactivity disorder and autism spectrum disorders: A meta-analysis of diffusion tensor imaging studies.

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) show common brain area abnormalities, which may contribute to the high shared co-occurrence symptoms and comorbidity of the two disorders. However, neuroanatomic anomalies in neurodevelopmental disorders may change over the course of development, and the developmental variation of these two disorders is unclear. Our study conducted a systematic literature search of PubMed, Web of Science, and EMBASE databases to identify disorder-shared abnormalities of white matter (WM) from childhood to adulthood in ADHD and ASD. 28 ADHD and 23 ASD datasets were included in this meta-analysis and were analysed by AES-SDM to detect differences in fractional anisotropy in patients compared to typically developing individuals. Our main findings reveal the variable WM developmental trajectories in ADHD and ASD respectively, and the two disorders showed overlapping corpus callosum tract abnormalities in their development from children to adults. Furthermore, the overlapping abnormalities of the corpus callosum tract increased with age, which may be related to their gradually increasing shared symptoms and comorbidity in these two disorders.

Behavioral and brain functional characteristics of children with Attention-Deficit/Hyperactivity disorder and anxiety trait.

The current study aimed to explore the behavioral, daily-life executive functional, and brain functional connectivity patterns in children with attention-deficit/hyperactivity disorder (ADHD) and anxiety. A total of 246 children with non-comorbid ADHD and 91 healthy controls (HCs) participated in the current study, among whom 175 subjects went through resting-state functional magnetic resonance imaging (fMRI) scans. The ADHD participants were divided into two subgroups: ADHD with a high level of anxiety (ADHD + ANX) and ADHD with a low level of anxiety (ADHD-ANX). The Child Behavior Checklist (CBCL) and the Behavior Rating Inventory of Executive Function (BRIEF) were used to capture the behavioral and daily-life executive functional characteristics. Independent component analysis with dual regression models was applied to the fMRI data. All statistical models were estimated with age and sex as covariates. Compared with the ADHD-ANX group, the ADHD + ANX group showed more withdrawn, somatic, social, thought, attention, delinquent, and aggressive problems (all corrected p < 0.05). The ADHD + ANX group also displayed more impaired emotional control and working memory than the ADHD-ANX (all corrected p < 0.05). The ADHD-ANX group, but not the ADHD + ANX group, showed elevated functional connectivity within the default mode network compared with the HC group. The mean function connectivity within the default mode network significantly mediated the correlation between anxiety level and attention problems. In sum, anxiety in children with ADHD was associated with more social, emotional, and behavioral problems, more impaired daily-life executive function, and altered brain function. Our work provides important information on the heterogeneity of ADHD.

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.

Reliability and validity of the Chinese version of the kiddie-schedule for affective disorders and schizophrenia-present and lifetime version DSM-5 (K-SADS-PL-C DSM-5).

BACKGROUND: As the Diagnostic and Statistical Manual of Mental Disorders fifth version (DSM-5) was published, the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL) was modified to adapt the new version (K-SADS-PL DSM-5). We translated it to Chinese (K-SADS-PL-C DSM-5) and described its reliability and validity. METHODS: A total of 154 groups of 6 to 18-year-old children and their guardians were included. Trained interviewers interviewed subjects using the K-SADS-PL-C DSM-5. Interrater reliability was assessed by audio recording. Parent-reported scales, like child behavior checklist (CBCL), the Chinese version of Swan-son Nolan and Pelham, version IV scale-parent form (SNAP-IV), social responsiveness scale (SRS-1), and children-reported scales like depression self-rating scale for children (DSRSC) and the screen for child anxiety related emotional disorders (SCARED) were used to examine the validity of depressive disorder, ADHD, ASD, and ODD. RESULTS: The K-SADS-PL-C DSM-5 had fair to excellent interrater (0.537-1.000) and test-retest (0.468-0.885) reliability of affective disorder and neurodevelopment disorder. The convergent validity of affective disorder and neurodevelopment disorder was good, and their divergent validity was acceptable. LIMITATIONS: i) Clinical questionnaires were insensitive in classifying disorders and had limitations in derived diagnoses. ii) Samples only came from clinical environment, iii) covered limited disease species, and iv) were small. CONCLUSION: The K-SADS-PL-C DSM-5 can support reliable and valid diagnoses for children with affect, neurodevelopmental, and behavioral disorders in China.

Shared and Unique Effects of Long-Term Administration of Methylphenidate and Atomoxetine on Degree Centrality in Medication-Naïve Children With Attention-Deficit/Hyperactive Disorder.

BACKGROUND: Although methylphenidate (MPH) and atomoxetine (ATX) can improve clinical symptoms and functional impairments in attention deficit/hyperactive disorder (ADHD), the underlying psychopharmacological mechanisms have not been clearly elucidated. Therefore, we aimed to explore the shared and unique neurologic basis of these 2 medications in alleviating the clinical symptoms and functional impairments observed in ADHD. METHODS: Sixty-seven ADHD and 44 age-matched children with typical development were included and underwent resting-state functional magnetic resonance imaging scans at baseline. Then patients were assigned to MPH, ATX, or untreated subgroups, based on the patients' and their parents' choice, for a 12-week follow-up and underwent a second functional magnetic resonance imaging scan. The treatment effect on degree centrality (DC) was identified and correlated with clinical symptoms and functional impairments in the ADHD group. RESULTS: Both MPH and ATX normalized the DC value in extensive brain regions mainly involving fronto-cingulo-parieto-cerebellum circuits. However, ATX showed limited significant effects on the cerebellum compared with ADHD at baseline. The improvements in clinical symptoms were correlated with increased DC in the right inferior temporal gyrus in both MPH and ATX subgroups but showed opposite effects. The alleviation of functional impairments in the school/learning domain negatively correlated with decreased DC in the bilateral cerebellum after MPH treatment, and the family functional domain positively correlated with decreased DC in the cerebellum and negatively correlated with decreased DC in the postcentral gyrus after ATX treatment. CONCLUSIONS: Both MPH and ATX can normalize abnormal brain functions that mainly involve the fronto-cingulo-parieto-cerebellum circuit in ADHD. Furthermore, the 2 medications showed shared and unique effects on brain functions to alleviate clinical symptoms and functional impairment.

Frequency-specific age-related changes in the amplitude of spontaneous fluctuations in autism.

Background: Autism spectrum disorder is characterized by atypical developmental changes during brain maturation, but regional brain functional changes that occur with age and across different frequency bands are unknown. Therefore, the current study aimed to explore potential age and frequency band-related changes in the regional brain activities in autism. Methods: A total of 65 participants who met the DSM-IV criteria for autistic disorder and 55 typically developed (TD) participants (both age 6-30 years) were recruited in the current study. The two groups were matched in age (t=-1.314, P=0.191) and gender (χ2=2.760, P=0.097). The amplitude of low-frequency fluctuations (ALFF) was employed to explore the effect of development on spontaneous brain activity in individuals with autism and in TD participants across slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), and slow-3 (0.073-0.1 Hz) frequency bands. The diagnosis-by-age interaction effect in the whole brain voxels in autism and TD groups was investigated. Results: Autism individuals showed significantly higher ALFF in the dorsal striatum in childhood (Caudate cluster: t=3.626, P=0.001; Putamen cluster: t=2.839, P=0.007) and remarkably lower ALFF in the dorsal striatum in adulthood (Caudate cluster: t=-2.198, P=0.038; Putamen cluster: t=-2.314, P=0.030) relative to TD, while no significant differences were observed in adolescence (all P>0.05). In addition, abnormal ALFF amplitudes were specific to the slow-4 (0.027-0.073 Hz) frequency band in the clusters above. Conclusions: The current study indicated abnormal development patterns in the spontaneous activity of the dorsal striatum in autism and highlighted the potential role of the slow-4 frequency band in the pathology of autism. Also, the potential brain mechanism of autism was revealed, suggesting that autism-related variations should be investigated in a specific frequency.

ADHD-inattentive versus ADHD-Combined subtypes: A severity continuum or two distinct entities? A comprehensive analysis of clinical, cognitive and neuroimaging data.

The current study aimed to explore the multimodal differences between the inattentive ADHD (ADHD-I) subtype and the combined ADHD (ADHD-C) subtype. A large sample of medication-naïve children with pure ADHD (i.e., without any comorbidity) (145 with ADHD-I, 132 with ADHD-C) and healthy controls (n = 98) were recruited. A battery of multiple scales and cognitive tests were utilized to assess the clinical and cognitive profiles of each individual. In addition, structural and diffusion magnetic resonance imaging (MRI) were acquired for 120 subjects with ADHD and 85 controls. Regional gray matter volume, white matter volume, and diffusion tensors, e.g., axial diffusivity (AD), were compared among the three groups in a whole-brain voxel-wise manner. Compared with healthy controls, both ADHD groups exhibited elevated levels of behavioral and emotional problems. The ADHD-C group had more behavioral problems and emotional liability, as well as less anxiety, than the ADHD-I group. The two ADHD groups were equally impaired in most cognitive domains, with the exception of sustained attention. Compared with healthy controls, the ADHD-C group showed a high gray matter volume (GMV) in the bilateral thalamus and a high white matter volume in the body of the corpus callosum, while the ADHD-I group presented an elevated GMV mainly in the left precentral gyrus and posterior cingulate cortex. Compared with participants with ADHD-C and healthy controls, subjects with ADHD-I showed increased AD in widespread brain regions. Our study has revealed a distinct, interconnected pattern of behavioral, cognitive, and brain structural characteristics in children with different ADHD subtypes.

Developmental brain structural atypicalities in autism: a voxel-based morphometry analysis.

BACKGROUND: Structural magnetic resonance imaging (sMRI) studies have shown atypicalities in structural brain changes in individuals with autism spectrum disorder (ASD), while a noticeable discrepancy in their results indicates the necessity of conducting further researches. METHODS: The current study investigated the atypical structural brain features of autistic individuals who aged 6-30 years old. A total of 52 autistic individuals and 50 age-, gender-, and intelligence quotient (IQ)-matched typically developing (TD) individuals were included in this study, and were assigned into three based cohorts: childhood (6-12 years old), adolescence (13-18 years old), and adulthood (19-30 years old). Analyses of whole-brain volume and voxel-based morphometry (VBM) on the sMRI data were conducted. RESULTS: No significant difference was found in the volumes of whole-brain, gray matter, and white matter between the autism and TD groups in the three age-based cohorts. For VBM analyses, the volumes of gray matter in the right superior temporal gyrus and right inferior parietal lobule in the autism group (6-12 years old) were smaller than those in the TD group; the gray matter volume in the left inferior parietal lobule in the autism group (13-18 years old) was larger than that in the TD group; the gray matter volume in the right middle occipital gyrus in the autism group (19-30 years old) was larger than that in the TD group, and the gray matter volume in the left posterior cingulate gyrus in the autism group was smaller than that in the TD group. CONCLUSION: Autistic individuals showed different atypical regional gray matter volumetric changes in childhood, adolescence, and adulthood compared to their TD peers, indicating that it is essential to consider developmental stages of the brain when exploring brain structural atypicalities in autism.

Efficacy and tolerability of antidepressant drugs in treatment of depression in children and adolescents: a network meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of antidepressants in treatment of depression disorder in children and adolescents by network meta-analysis. METHODS: Databases of PubMed, Cochrane Library, EMBASE, Web of Science, PsycINFO, CBM, CNKI and Wanfang Data were searched for randomized controlled trials (RCT) related to antidepressants in treatment of children and adolescents with depression from inception to December 2021. Quality assessment and data extraction from the included RCTs were performed. Statistical analyses of efficacy and tolerability were conducted with Stata 15.1 software. Surface under the cumulative ranking (SUCAR) was used to rank the value of the antidepressants. RESULTS: A total of 33 RCTs were included in 32 articles, involving 6949 patients. There are 13 antidepressants used in total, including amitriptyline, vilazodone, fluoxetine, selegiline, paroxetine, imipramine, desipramine, sertraline, nortriptyline, escitalopram, citalopram, venlafaxine and duloxetine. The results of network meta-analysis showed that the efficacy of duloxetine ( OR=1.95, 95% CI: 1.41-2.69), fluoxetine ( OR=1.73, 95% CI: 1.40-2.14), venlafaxine ( OR=1.37, 95% CI: 1.04-1.80) and escitalopram ( OR=1.48, 95% CI: 1.12-1.95) were significantly higher than that of placebos (all P<0.05); the probability cumulative ranks were duloxetine (87.0%), amitriptyline (83.3%), fluoxetine (79.0%), escitalopram (62.7%), etc. The results showed that the intolerability of patients receiving imipramine ( OR=0.15, 95% CI: 0.08-0.27), sertraline ( OR=0.33, 95% CI: 0.16-0.71), venlafaxine ( OR=0.35, 95% CI: 0.17-0.72), duloxetine ( OR=0.35, 95% CI: 0.17-0.73) and paroxetine ( OR=0.52, 95% CI: 0.30-0.88) were significantly higher than that of placebos (all P<0.05), and the probability cumulative ranks were imipramine (95.7%), sertraline (69.6%), venlafaxine (68.6%), duloxetine (68.2%), etc. Conclusion: Among 13 antidepressants, duloxetine, fluoxetine, escitalopram and venlafaxine are significantly better than placebo in terms of efficacy, but duloxetine and venlafaxine are less well tolerated.

Atypicalities in the developmental trajectory of cortico-striatal functional connectivity in autism spectrum disorder.

LAY ABSTRACT: Autism spectrum disorder has long been conceptualized as a disorder of "atypical development of functional brain connectivity (which refers to correlations in activity levels of distant brain regions)." However, most of the research has focused on the connectivity between cortical regions, and much remains unknown about the developmental changes of functional connectivity between subcortical and cortical areas in autism spectrum disorder. We used the technique of resting-state functional magnetic resonance imaging to explore the developmental characteristics of intrinsic functional connectivity (functional brain connectivity when people are asked not to do anything) between subcortical and cortical regions in individuals with and without autism spectrum disorder aged 6-30 years. We focused on one important subcortical structure called striatum, which has roles in motor, cognitive, and affective processes. We found that cortico-striatal intrinsic functional connectivities showed opposite developmental trajectories in autism spectrum disorder and typically developing individuals, with connectivity increasing with age in autism spectrum disorder and decreasing or constant in typically developing individuals. We also found significant negative behavioral correlations between those atypical cortico-striatal intrinsic functional connectivities and autistic symptoms, such as social-communication deficits, and restricted/repetitive behaviors and interests. Taken together, this work highlights that the atypical development of cortico-subcortical functional connectivity might be largely involved in the neuropathological mechanisms of autism spectrum disorder.

Identify aberrant white matter microstructure in ASD, ADHD and other neurodevelopmental disorders: A meta-analysis of diffusion tensor imaging studies.

BACKGROUND: Neurodevelopmental disorders (NDDs) usually present overlapping symptoms. Abnormal white matter (WM) microstructure has been found in these disorders. Identification of common and unique neural abnormalities across NDDs could provide further insight into the underlying pathophysiological mechanisms. METHODS: We performed a voxel-based meta-analysis of whole-brain diffusion tensor imaging (DTI) studies in autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and other NDDs. A systematic literature search was conducted through March 2020 to identify studies that compared measures of WM microstructure between patients with NDDs and neurotypical controls. Peak voxel coordinates were meta-analyzed via anisotropic effect size-signed differential mapping (AES-SDM) as well as activation likelihood estimation (ALE). RESULTS: Our final sample included a total of 4137 subjects from 66 studies across five NDDs. Fractional anisotropy (FA) reductions were found in the splenium of the CC in ADHD, and the genu and splenium of CC in ASD. And mean diffusivity (MD) increases were shown in posterior thalamic radiation in ASD. No consistent abnormalities were detected in specific learning disorder, motor disorder or communication disorder. Significant differences between child/adolescent and adult patients were found within the CC across NDDs, reflective of aberrant neurodevelopmental processes in NDDs. CONCLUSIONS: The current study demonstrated atypical WM patterns in ASD, ADHD and other NDDs. Microstructural abnormalities in the splenium of the CC were possibly shared among ASD and ADHD.

Functional abnormality in the sensorimotor system attributed to NRXN1 variants in boys with attention deficit hyperactivity disorder.

Impaired sensorimotor circuits have been suggested in Attention-deficit/hyperactivity disorder (ADHD). NRXN1, highly expressed in cortex and cerebellum, was one of the candidate risk genes for ADHD, while its effects on sensorimotor circuits are unclear. In this content, we aimed to investigate the differential brain effects as functions of the cumulative genetic effects of NRXN1 variants in ADHD and healthy controls (HCs), identifying a potential pathway mapping from NRXN1, sensorimotor circuits, to ADHD. Magnetic resonance imaging, blood samples and clinical assessments were acquired from 53 male ADHD and 46 sex-matched HCs simultaneously. The effects of the cumulative genetic effects of NRXN1 variants valued by poly-variant risk score (PRS), on brain function was measured by resting-state functional connectivity (rs-FC) of cerebrocerebellar circuits. Mediation analyses were conducted to evaluate the association between NRXN1, functional abnormality, and ADHD diagnosis, as well as ADHD symptoms. The results were validated by bootstrapping and 10,000 times permutation tests. The rs-FC analyses demonstrated significant mediation models for ADHD diagnosis, and emphasized the involvement of cerebellum, middle cingulate gyrus and temporal gyrus, which are crucial parts of sensorimotor circuits. The current study suggested NRXN1 conferred risk for ADHD by regulating the function of sensorimotor circuits.

Cortical Morphometric Abnormality and Its Association with Working Memory in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents. The present study investigated the cortical morphology features and their relationship with working memory (WM). METHODS: In the present study, a total of 36 medication naïve children with ADHD (aged from 8 to 15 years) and 36 age- and gendermatched healthy control (HC) children were included. The digit span test was used to evaluate WM. The magnetic resonance imaging (MRI) was used to examine the characteristics of cortical morphology. Firstly, we compared the cortical morphology features between two groups to identify the potential structural alterations of cortical volume, surface, thickness, and curvature in children with ADHD. Then, the correlation between the brain structural abnormalities and WM was further explored in children with ADHD. RESULTS: Compared with the HC children, the children with ADHD showed reduced cortical volumes in the left lateral superior temporal gyrus (STG) (p=6.67×10-6) and left anterior cingulate cortex (ACC) (p=3.88×10-4). In addition, the cortical volume of left lateral STG was positively correlated with WM (r=0.36, p=0.029). CONCLUSION: Though preliminary, these findings suggest that the reduced cortical volumes of left lateral STG may contribute to the pathogenesis of ADHD and correlate with WM in children with ADHD.