An investigation of the acute effects of aerobic exercise on executive function and cortical excitability in adolescents with attention deficit hyperactivity disorder (ADHD).

Previous studies have shown that aerobic exercise has beneficial effects on executive function in adolescents with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms could be partially due to aerobic exercise-induced cortical excitability modulation. The aim of this study was to explore the effects of acute aerobic exercise on executive functions and cortical excitability and the association between these phenomena in adolescents with ADHD. The study was conducted using a complete crossover design. Executive functions (inhibitory control, working memory, and planning) and cortical excitability were assessed in twenty-four drug-naïve adolescents with ADHD before and after acute aerobic exercise or a control intervention. Inhibitory control, working memory, and planning improved after acute aerobic exercise in adolescents with ADHD. Moreover, cortical excitability monitored by transcranial magnetic stimulation (TMS) decreased after intervention in this population. Additionally, improvements in inhibitory control and working memory performance were associated with enhanced cortical inhibition. The findings provide indirect preliminary evidence for the assumption that changes in cortical excitability induced by aerobic exercise partially contribute to improvements in executive function in adolescents with ADHD.

Acute aerobic exercise at different intensities modulates inhibitory control and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD).

BACKGROUND: This study aimed to investigate the effects of different aerobic exercise intensities on inhibitory control and cortical excitability in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: The study was conducted in a within-subject design. Twenty-four adults with ADHD completed a stop signal task and received cortical excitability assessment by transcranial magnetic stimulation (TMS) before and after a single session of low-, moderate-, high-intensity aerobic exercise or a control intervention. RESULTS: Acute moderate-, and high-intensity aerobic exercise improved inhibitory control in adults with ADHD. Moreover, the improving effect was similar between moderate-, and high-intensity aerobic exercise conditions. As shown by the brain physiology results, short interval intracortical inhibition was significantly increased following both, moderate- and high-intensity aerobic exercise intervention conditions. Additionally, the alteration of short interval intracortical inhibition and inhibitory control improvement were positively correlated. CONCLUSIONS: The moderate-, and high-intensity aerobic exercise-dependent alterations of cortical excitability in adults with ADHD might partially explain the inhibitory control-improving effects of aerobic exercise in this population.

Factors mediating pre-existing autism diagnosis and later suicidal thoughts and behaviors: A follow-up cohort study.

LAY ABSTRACT: Autistic people are more likely to experience suicidal thoughts and behaviors. The underlying relationships between potential risk factors and suicidal thoughts and behaviors in autistic individuals remain unclear. To understand this, we investigated whether specific factors in childhood/youth explain the effects of pre-existing autism spectrum disorder (ASD) diagnoses on later suicidal thoughts and behaviors in adolescence/adulthood. We assessed internalizing and externalizing problems, bullying experiences, and executive functions (including cognitive flexibility, sustained attention, and spatial working memory) at an average baseline age of 13.4 years and suicidal thoughts and behaviors at an average follow-up age of 19.2 years among 129 autistic and 121 typically developing (TD) individuals. During the follow-up period in adolescence/adulthood, autistic individuals were more likely to report suicidal thoughts than TD individuals. Being bullied partially accounted for the relationship between a pre-existing ASD diagnosis and later-reported higher suicidal thoughts. Contrary to our hypothesis, higher (instead of lower) cognitive flexibility in some autistic young people appeared to partially explain their higher rates of suicidal thoughts compared with typically developing young people. The findings imply that school bullying prevention and tailored intervention programs for autistic people, especially those with higher cognitive flexibility, are warranted to reduce their risks of experiencing suicidal thoughts.

Distinct developmental changes in regional gray matter volume and covariance in individuals with attention-deficit hyperactivity disorder: A longitudinal voxel-based morphometry study.

BACKGROUND: Very few studies have investigated longitudinal clinical cohorts of attention-deficit/hyperactivity disorder (ADHD). Moreover, how baseline brain changes could affect the development of ADHD symptoms later in life remains elusive. Therefore, we aimed to fill this gap by exploring brain and clinical changes in youth with ADHD using a longitudinal design. METHODS: This prospective study consisted of 74 children and adolescents with ADHD and 50 age-, sex-, intelligence-matched typically developing controls (TDC), evaluated at baseline (aged 7-19 years) and re-evaluated 5.3 years later (a mean follow-up latency). We applied voxel-based morphometry to characterize brain structures, followed by both mass-univariate and multivariate structural covariance statistics to identify brain regions with significant diagnosis-by-time interactions from late childhood/adolescence to early adulthood. We used the cross-lagged panel model to investigate the longitudinal association between structural brain metrics and core ADHD symptoms. RESULTS: The mass-univariate statistic revealed significant diagnosis-by-time interactions in the right striatum and the sixth lobule of the cerebellum. This was expressed by increased striatal and decreased cerebellar volume in ADHD, while TDC showed inverse volume changes over time. The multivariate method showed significant diagnosis-by-time interactions in a structural covariance network consisting of the regions involved in the functional sensory-motor and default-mode networks. Higher baseline right striatal and cerebellar volumes were associated with elevated ADHD symptoms at follow-up. CONCLUSIONS: Our findings suggest a temporal association between the divergent development of striatal and cerebellar regions and dynamical ADHD phenotypic expression through young adulthood. These results highlight a potential brain marker of future outcomes.

Treatment-resistant depression in children and adolescents.

Major depressive disorder (MDD) in children and adolescents is a significant health problem, causing profound impairments in social, academic, and family functioning and substantial morbidity and mortality. Up to 15% of children and adolescents suffer from MDD, and a proportion, around 30 to 40% of them, failed to respond to initial selective serotonin reuptake inhibitor (SSRI) treatment. The only evidence-based recommendation is medication switching to another SSRI and augmentation with cognitive behavioral therapy. Newly developing treatment, including ketamine, transcranial magnetic stimulation, psychotherapy other than cognitive behavioral therapy, and combined pharmacotherapy with other interventions, requires further longitudinal controlled trials regarding efficacy and safety in this vulnerable population.

Psychometric properties of the Mandarin version of the autism diagnostic observation Schedule-Generic.

BACKGROUND/PURPOSE: The diagnosis of autism spectrum disorder (ASD), involving multiple components of clinical assessments, is challenging. The Autism Diagnostic Observation Schedule-Generic (ADOS-G), one of the standardized and validated instruments for ASD diagnostic evaluation, has been widely used in many countries. With the preparation of the Mandarin version of the ADOS-G (Mandarin-ADOS-G), this study aims to examine its psychometric properties, including reliability and validity. METHODS: The sample included 554 individuals clinically diagnosed with ASD (477 males, 86.1%) and 50 typically developing (TD) individuals (29 males, 58.0%) who were assessed with different modules of the Mandarin-ADOS-G between 4.1 and 34.0 years old with a mean age of 13.0 years (Module 1, n = 40; Module 2, n = 46; Module 3, n = 275; Module 4, n = 243). We evaluated the inter-rater reliability, test-retest reliability, internal consistency, and concurrent validity with the Chinese Autism Diagnostic Interview-Revised (ADI-R) and Social Responsiveness Scale (SRS) caregiver-report and self-report forms. The discriminative validity of Mandarin-ADOS-G was also examined. RESULTS: The Mandarin-ADOS-G demonstrated good inter-rater reliability (agreement of ADOS classification 0.91), good test-retest reliability (intraclass correlations 0.55-0.73), and low to high good internal consistency (Cronbach's alpha 0.27-0.86). The concurrent validity showed significant correlations with ADI-R (Pearson correlations 0.22-0.37) and the SRS caregiver-report form (Pearson correlations 0.15-0.23). Moreover, all Mandarin-ADOS-G domains successfully differentiated autistic individuals from TD individuals (all p-values <0.001). CONCLUSION: The Mandarin-ADOS-G is a reliable and valid instrument for assisting the diagnosis of ASD in the Mandarin-speaking population.

White matter microstructural and morphometric alterations in autism: implications for intellectual capabilities.

BACKGROUND: Neuroimage literature of autism spectrum disorder (ASD) has a moderate-to-high risk of bias, partially because those combined with intellectual impairment (II) and/or minimally verbal (MV) status are generally ignored. We aimed to provide more comprehensive insights into white matter alterations of ASD, inclusive of individuals with II (ASD-II-Only) or MV expression (ASD-MV). METHODS: Sixty-five participants with ASD (ASD-Whole; 16.6 ± 5.9 years; comprising 34 intellectually able youth, ASD-IA, and 31 intellectually impaired youth, ASD-II, including 24 ASD-II-Only plus 7 ASD-MV) and 38 demographic-matched typically developing controls (TDC; 17.3 ± 5.6 years) were scanned in accelerated diffusion-weighted MRI. Fixel-based analysis was undertaken to investigate the categorical differences in fiber density (FD), fiber cross section (FC), and a combined index (FDC), and brain symptom/cognition associations. RESULTS: ASD-Whole had reduced FD in the anterior and posterior corpus callosum and left cerebellum Crus I, and smaller FDC in right cerebellum Crus II, compared to TDC. ASD-IA, relative to TDC, had no significant discrepancies, while ASD-II showed almost identical alterations to those from ASD-Whole vs. TDC. ASD-II-Only had greater FD/FDC in the isthmus splenium of callosum than ASD-MV. Autistic severity negatively correlated with FC in right Crus I. Nonverbal full-scale IQ positively correlated with FC/FDC in cerebellum VI. FD/FDC of the right dorsolateral prefrontal cortex showed a diagnosis-by-executive function interaction. LIMITATIONS: We could not preclude the potential effects of age and sex from the ASD cohort, although statistical tests suggested that these factors were not influential. Our results could be confounded by variable psychiatric comorbidities and psychotropic medication uses in our ASD participants recruited from outpatient clinics, which is nevertheless closer to a real-world presentation of ASD. The outcomes related to ASD-MV were considered preliminaries due to the small sample size within this subgroup. Finally, our study design did not include intellectual impairment-only participants without ASD to disentangle the mixture of autistic and intellectual symptoms. CONCLUSIONS: ASD-associated white matter alterations appear driven by individuals with II and potentially further by MV. Results suggest that changes in the corpus callosum and cerebellum are key for psychopathology and cognition associated with ASD. Our work highlights an essential to include understudied subpopulations on the spectrum in research.

Mental health correlates and potential childhood predictors for the wish to be of the opposite sex in young autistic adults.

LAY ABSTRACT: Autistic people/people with autism spectrum disorder are more likely to experience gender dysphoria. However, the possible longitudinal predictors and underlying mechanisms of this co-occurrence are unclear. To fill this knowledge gap, we assessed 88 people with autism spectrum disorder and 42 typically developing individuals at their average ages of 13.0 (baseline, childhood/adolescence) and 20.2 years old (follow-up, adulthood). At follow-up, their endorsement on the item "I wish I was the opposite sex" was used to evaluate gender dysphoric symptoms. We compared mental health symptoms between adults with and without this item endorsement at the follow-up assessment. We explored parent-reported family and autism characteristics-related predictors in childhood/adolescence to this item endorsement in adulthood. We found that more autistic adults reported the wish to be of the opposite sex than did typically developing individuals. Autistic adults who endorsed this item experienced more mental health challenges, more school bullying and cyberbullying, more suicidal ideation, and worse quality of life. Moreover, parent-reported lower family support and more stereotyped/repetitive behaviors during childhood/adolescence predicted the self-reported wish to be of the opposite sex in adulthood in autistic individuals. More attention and support should be provided to autistic people regarding gender development and related mental health and quality of life impact, especially during the transition period to young adulthood.

Heart Rate Variability Reactivity to Food Image Stimuli is Associated with Body Mass Index.

Appetitive control is driven by the hedonic response to food and affected by several factors. Heart rate variability (HRV) signals have been used to index autonomic activity and arousal levels towards visual stimuli. The current research aimed to examine the influence of body mass index (BMI), disordered eating behaviors, and sex on the HRV reactivity to food in a nonclinical sample. Thirty-eight healthy male and sixty-one healthy female participants completed questionnaires assessing disordered eating symptoms. HRV was recorded when the participants received visual stimuli of high-calorie food, neutral and negative emotional signals. Generalized estimating equation models were used to investigate the associations between HRV, BMI, disordered eating behaviors, and sex across the three stimulus types. Male participants demonstrated a higher ratio of low-frequency power to high-frequency power (LF/HF) than females across all the stimulus types. An increase in LF/HF reactivity to food signals was observed in all the study subjects. The moderation effect of BMI on LF/HF in response to food signals was also observed. Our study suggests that body weight may play a role in the interaction between sympathetic activity and food stimuli; however, how the interaction between sympathetic activity and food stimuli contributes to diet control warrants further investigation.

Regional brain volume predicts response to methylphenidate treatment in individuals with ADHD.

BACKGROUND: Despite the effectiveness of methylphenidate for treating ADHD, up to 30% of individuals with ADHD show poor responses to methylphenidate. Neuroimaging biomarkers to predict medication responses remain elusive. This study characterized neuroanatomical features that differentiated between clinically good and poor methylphenidate responders with ADHD. METHODS: Using a naturalistic observation design selected from a larger cohort, we included 79 drug-naive individuals (aged 6-42 years) with ADHD without major psychiatric comorbidity, who had acceptable baseline structural MRI data quality. Based on a retrospective chart review, we defined responders by individuals' responses to at least one-month treatment with methylphenidate. A nonparametric mass-univariate voxel-based morphometric analysis was used to compare regional gray matter volume differences between good and poor responders. A multivariate pattern recognition based on the support vector machine was further implemented to identify neuroanatomical indicators to predict an individual's response. RESULTS: 63 and 16 individuals were classified in the good and poor responder group, respectively. Using the small-volume correction procedure based on the hypothesis-driven striatal and default-mode network masks, poor responders had smaller regional volumes of the left putamen as well as larger precuneus volumes compared to good responders at baseline. The machine learning approach identified that volumetric information among these two regions alongside the left frontoparietal regions, occipital lobes, and posterior/inferior cerebellum could predict clinical responses to methylphenidate in individuals with ADHD. CONCLUSION: Our results suggest regional striatal and precuneus gray matter volumes play a critical role in mediating treatment responses in individuals with ADHD.

Comparisons of the clinical outcomes between early- and adult-onset bipolar disorders: A prospective cohort analysis.

BACKGROUND: This study aimed to explore the impact of age-at-onset on clinical outcomes in bipolar-spectrum disorders, including the development of alcohol or substance use disorder, suicidality, and psychiatric hospitalization. METHODS: This population-based study enrolled newly-diagnosed bipolar-spectrum patients, including 4,367 patients with early-onset bipolar disorder (EOBD), 64,787 patients with adult-onset bipolar disorder (AOBD), and the same number of age-controlled comparison subjects without bipolar disorder, from Taiwan's National Health Insurance Research Database. Time-dependent covariate Cox regression models were used to estimate the effect of age-at-onset on clinical outcomes with adjustment for pre-existing psychiatric comorbid conditions and pharmacological treatment patterns. Sensitivity analyses using different definitions of study sample and age cutoffs were conducted. RESULTS: The average follow-up duration was 5.7 years. After adjustment with time-dependent covariates and chronological age, there were no significant differences in the risks for developing new-onset alcohol or substance use disorders and psychiatric hospitalization between EOBD and AOBD patients. Although EOBD patients had a higher risk of hospitalization for suicide and self-harm than did AOBD patients in primary analysis, this finding did not replicated in the sensitivity analyses. LIMITATIONS: The symptom profile and severity of bipolar disorder was not available in the NHIRD; therefore, surrogate indicators of clinical outcome might not be sensitive enough to detect the subtle differences. CONCLUSIONS: EOBD and AOBD patients had similar risks for developing alcohol or substance use disorders. Their risk of psychiatric hospitalization was similar. Whether EOBD patients might have a higher risk of hospitalization for suicide and self-harm warrants further investigations.

The mental health of immigrant mother's offspring in Taiwan: A national epidemiological study.

BACKGROUND/PURPOSE: With globalization, transnational marriages become more and more common in the world. The mental health of the offspring of immigrants is a significant public health issue. The present study aimed to investigate whether children of immigrant mothers demonstrate more emotional and behavioral problems than those of native mothers in Taiwan. METHODS: In a sample of 6242 children in grade 3, grade 5, and grade 7 from a national epidemiological study of child mental disorders, 617 (9.9%) children were born by immigrant mothers (Chinese, Vietnam, Indonesia, and other countries) and 5625 children by Taiwanese parents. The children reported on Achenbach Youth Self-report, and their parents reported about them on the Child Behavior Checklist, Parental Bonding Inventory, and Family APGAR for assessing emotional and behavioral problems, mother's parenting style, and perceived family support. RESULTS: Compared with children of native mothers, children of immigrant mothers reported themselves and were reported by their parents to have more externalizing and internalizing problems. However, after considering the effects of sociodemographics, parenting style, and family function, only significant differences in externalizing problems between children with native or immigrant mothers were found. CONCLUSION: Our findings indicate that right parenting style and family support; may offset emotional and behavioral problems in children of immigrant mothers, and suggest that improving maternal parenting and family function is beneficial to child development, regardless of immigrant or native mothers.

Vertical distribution of source apportioned PM2.5 using particulate-bound elements and polycyclic aromatic hydrocarbons in an urban area.

Receptor models have been widely used for identifying and quantifying source-specific contributions from mixtures of air pollutants. Nonetheless, our knowledge is still limited on how various components of air pollution are vertically distributed and the sources of such pollutants. In this study, we collected 135 samples of PM2.5 (particles with aerodynamic diameter less than or equal to 2.5 µm) from building balconies at three altitudes in the metropolis of Taipei (Taiwan) and analyzed the samples for elements and polycyclic aromatic hydrocarbons that could be used to identify the sources of those pollutants. We used positive matrix factorization (PMF) to identify seven likely sources, including combustion, sulfur-rich aerosol, fresh traffic, industry/Cr-rich, oil combustion/vehicle, dust, and traffic. Although PM2.5 mass differed significantly between low-level and mid-level sites, the largest contributor to PM2.5 mass (sulfur-rich aerosol, 35.2%) showed nonsignificant variation in the vertical distribution. In contrast, oil combustion/vehicle, which exhibited significant difference between mid-level sites and the other two altitudes, might be a determinant in the vertical variation of PM2.5. We also observed negative trends with sampling height for combustion and traffic emissions.