ADGRL3 (LPHN3) variants are associated with a refined phenotype of ADHD in the MTA study

Background ADHD is the most common neuropsychiatric condition affecting individuals of all ages. Long-term outcomes of affected individuals and association with severe comorbidities as SUD or conduct disorders are the main concern. Genetic associations have been extensively described. Multiple studies show that intronic variants harbored in the ADGRL3 (LPHN3) gene are associated with ADHD, especially associated with poor outcomes. Methods In this study, we evaluated this association in the Multimodal Treatment Study of children with ADHD (MTA), initiated as a 14-month randomized clinical trial of 579 children diagnosed with DSM-IV ADHD-Combined Type (ADHD-C), that transitioned to a 16-year prospective observational follow-up, and 289 classmates added at the 2-year assessment to serve as a local normative comparison group (LNCG). Diagnostic evaluations at entry were based on the Diagnostic Interview Schedule for Children-Parent (DISC-P), which was repeated at several points over the years. For an add-on genetic study, blood samples were collected from 232 in the MTA group and 139 in the LNCG. Results For the 205 MTA participants, 14.6% retained the DISC-P diagnosis of ADHD-C in adolescence. For 127 LNCG participants, 88.2% remained undiagnosed by the DISC-P. We genotyped 15 polymorphic SNP markers harbored in the ADGRL3 gene, and compared allele frequencies for the 30 cases with continued diagnosis of ADHD-C in adolescence to the other participants. Replication of the association of rs2345039 ADGRL3 variant was observed (P value = 0.004, FDR corrected = 0.03; Odds ratio = 2.25, upper CI 1.28–3.97). Conclusion The detection of susceptibility conferred by ADGRL3 variants in the extreme phenotype of continued diagnosis of ADHD-C from childhood to adolescence provides additional support that the association of ADGRL3 and ADHD is not spurious. Exploring genetic effects in longitudinal cohorts, in which refined, age-dependent phenotypes are documented, is crucial to understand the natural history of ADHD

Psychotic symptoms in ADHD:an analysis of the MTA database

Objective: To assess the prevalence of psychotic symptoms among youths (age 14-25 years) with a childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) combined type. Method: The participants in the Multimodal Treatment Study of Children with ADHD (MTA) and a local normative comparison group (LNCG) were systematically assessed 6, 8, 10, 12, 14, and 16 years after the original enrollment at a mean age of 8.5 years. Trained research assistants administered a psychosis screener, and positive screens were referred to study clinicians to confirm or exclude psychosis. Possible associations between screening positive and alcohol or substance use were assessed. Results: Data were available from 509 MTA participants (88% of the original MTA sample) and 276 LNCG subjects (96% of the original sample), with a mean age of 25.1 and 24.6 years, respectively, at Year 16. Twenty-six MTA subjects (5%, 95% CI: 3, 7) and 11 LNCG (4%, 95% CI: 2, 6) screened positive for at least one psychotic symptom (p=0.60). Most psychotic symptoms were transient. The prevalence of clinician-confirmed psychotic symptoms was 1.1% (95% C.I. 0.2, 2.1) in the MTA and 0.7% (0, 1.7) in the LNCG (p=0.72). Greater cannabis use was reported by those who screened (p<0.05) and were confirmed positive (p<0.01). Conclusions: There was no evidence that ADHD increased the risk for psychotic symptoms. In both the ADHD and normative comparison groups, more frequent cannabis use was associated with greater likelihood of experiencing psychotic symptoms, thus supporting the recommendation that youth should not use cannabis

The Role of Animal Assisted Intervention on Improving Self-Esteem in Children With Attention Deficit/Hyperactivity Disorder

Attention Deficit/Hyperactivity Disorder (ADHD), the most ubiquitous mental health problem in children, has been associated with poor self-esteem. Psychosocial interventions have aimed to improve self-esteem among this group, with the aim of reducing the development of comorbid depression and anxiety. The present study implemented a randomized control design to examine the possibility of Animal Assisted Interventions (AAI) as a viable approach to improving self-esteem among children with ADHD. Children's self-esteem across multiple domains as measured by the Self-Perception Profile for Children was evaluated (n = 80, ages 7–9, 71% male). To test the hypothesis that AAI improves self-esteem, stratified Wilcoxon Signed-Rank Tests (SAS NPAR1WAY procedure) were used to compare pre- to post-treatment ratings. Analyses indicated that scores of children's self-perceptions in the domains of behavioral conduct, social, and scholastic competence, were significantly increased from baseline to post-treatment in the AAI group (z = 2.320, p = .021, z = 2.631, p = .008, and z = 2.541, p = .011, respectively), whereas pre-post-treatment differences in self-perceptions were not found for the children in the control group without AAI. Findings suggest that AAI is a viable strategy for improving ratings of self-perceived self-esteem in children with ADHD

Phase synchronization of oxygenation waves in the frontal areas of children with attention-deficit hyperactivity disorder detected by optical diffusion spectroscopy correlates with medication

The beneficial effects of pharmacotherapy on children with attention-deficit hyperactivity disorder (ADHD) are well documented. We use near-infrared spectroscopy (NIRS) methodology to determine reorganization of brain neurovascular properties following the medication treatment. Twenty-six children with ADHD (ages six through 12) participated in a modified laboratory school protocol to monitor treatment response with lisdexamfetamine dimesylate (LDX; Vyvanse®, Shire US Inc.). All children refrained from taking medication for at least two weeks (washout period). To detect neurovascular reorganization, we measured changes in synchronization of oxy ([Formula: see text]) and deoxy (HHb) hemoglobin waves between the two frontal lobes. Participants without medication displayed average baseline [Formula: see text] phase difference at about [Formula: see text]. and HHb differences at about 240-deg.. This phase synchronization index changed after pharmacological intervention. Medication induced an average phase changes of [Formula: see text] after first medication to 280-deg. and after medication optimization to 242-deg.. Instead first medication changed of the average HHb phase difference at 186-deg. and then after medication optimization to 120-deg. In agreement with findings of White et al., and Varela et al., we associated the phase synchronization differences of brain hemodynamics in children with ADHD with lobe specific hemodynamic reorganization of [Formula: see text]- and HHB oscillations following medication status

Phase synchronization of oxygenation waves in the frontal areas of children with attention-deficit hyperactivity disorder detected by optical diffusion spectroscopy correlates with medication.

The beneficial effects of pharmacotherapy on children with attention-deficit hyperactivity disorder (ADHD) are well documented. We use near-infrared spectroscopy (NIRS) methodology to determine reorganization of brain neurovascular properties following the medication treatment. Twenty-six children with ADHD (ages six through 12) participated in a modified laboratory school protocol to monitor treatment response with lisdexamfetamine dimesylate (LDX; Vyvanse®, Shire US Inc.). All children refrained from taking medication for at least two weeks (washout period). To detect neurovascular reorganization, we measured changes in synchronization of oxy (HbO2) and deoxy (HHb) hemoglobin waves between the two frontal lobes. Participants without medication displayed average baseline HbO2 phase difference at about -7-deg. and HHb differences at about 240-deg.. This phase synchronization index changed after pharmacological intervention. Medication induced an average phase changes of HbO2 after first medication to 280-deg. and after medication optimization to 242-deg.. Instead first medication changed of the average HHb phase difference at 186-deg. and then after medication optimization to 120-deg. In agreement with findings of White et al., and Varela et al., we associated the phase synchronization differences of brain hemodynamics in children with ADHD with lobe specific hemodynamic reorganization of HbO2- and HHB oscillations following medication status

Observation of human-animal interaction for research (OHAIRE) behavior coding in a randomized control trial of children with attention-deficit hyperactivity disorder (ADHD) and a canine-assisted intervention.

INTRODUCTION: Diagnosed in about 10% of children in the United States, attention-deficit hyperactivity disorder (ADHD) is characterized by symptoms including inattention, hyperactivity, and impulsivity. Traditional interventions, such as pharmacological and psychological interventions, are often used in conjunction with integrative health options, such as animal-assisted interventions. The objective of this manuscript is to report behavior coding findings from a randomized control trial of children with ADHD. METHODS: As part of a larger randomized control trial focused on the efficacy of combining a canine-assisted intervention (live therapy dog or control stuffed dog) with cognitive behavioral therapy for children with ADHD, the current manuscript focuses on video-captured behavior observations (n = 35 children, approximately 322 minutes of data). Data were extracted and coded using the Observation of Human-Animal Interaction Research (OHAIRE) Coding System. Behavior codes are reported as summary scores for the following domains: animal social interaction and human social interaction (further separated into human-adult social interaction and human-peer social interaction). Repeated measures mixed models analyses were performed using SAS PROC GLIMMIX to evaluate group differences and change across the study period. RESULTS: There were no significant differences in how much children interacted with the live therapy dogs versus control stuffed dogs. With respect to human-to-human social interactions, children showed greater increases over time in human-directed social interactions in the presence of live therapy dogs compared to stuffed dogs (p = .020). Over the course of the 12-week intervention, children increased in interactions with both adults (p = .006) and their peers (p = .014); however, there were more increases over time in adult-directed social interactions in the live animal condition compared to the control stuffed animal condition (p &lt; 0.0001). DISCUSSION &amp; CONCLUSIONS: Findings suggest changes in social interaction when participating in this canine-assisted intervention, specifically greater increases in human-to-human social interactions over time when a live therapy dog is present compared to a control stuffed dog. Children appear to engage relatively equally with both live and stuffed dogs; however, the impact of animals on human socialization differs based on if a live animal is present. Future studies should consider incorporating behavior coding analysis into studies of canine-assisted interventions to identify how human-animal interactions may be moderators or mechanisms for psychosocial outcomes

Utilizing Big Data From Google Trends to Map Population Depression in the United States: Exploratory Infodemiology Study

BackgroundThe epidemiology of mental health disorders has important theoretical and practical implications for health care service and planning. The recent increase in big data storage and subsequent development of analytical tools suggest that mining search databases may yield important trends on mental health, which can be used to support existing population health studies. ObjectiveThis study aimed to map depression search intent in the United States based on internet-based mental health queries. MethodsWeekly data on mental health searches were extracted from Google Trends for an 11-year period (2010-2021) and separated by US state for the following terms: “feeling sad,” “depressed,” “depression,” “empty,” “insomnia,” “fatigue,” “guilty,” “feeling guilty,” and “suicide.” Multivariable regression models were created based on geographic and environmental factors and normalized to the following control terms: “sports,” “news,” “google,” “youtube,” “facebook,” and “netflix.” Heat maps of population depression were generated based on search intent. ResultsDepression search intent grew 67% from January 2010 to March 2021. Depression search intent showed significant seasonal patterns with peak intensity during winter (adjusted P<.001) and early spring months (adjusted P<.001), relative to summer months. Geographic location correlated with depression search intent with states in the Northeast (adjusted P=.01) having higher search intent than states in the South. ConclusionsThe trends extrapolated from Google Trends successfully correlate with known risk factors for depression, such as seasonality and increasing latitude. These findings suggest that Google Trends may be a valid novel epidemiological tool to map depression prevalence in the United States

Assessment of Dosing and Patient Factors on the Efficacy of Warfarin Following Total Joint Replacement.

The purpose of this study was to determine the percentage of patients discharged with a subtherapeutic INR &lt;1.8 using our institutions inpatient warfarin dosing nomogram following total joint arthroplasty (TJA). We examined predisposing risk factors for a subtherapeutic discharge (INR &lt;1.8), including increased body weight, age, gender, end stage renal disease (ESRD), smoking, and peri-operative transfusion. Chart review identified 249 patients for study inclusion. Logistic regression (LR) was used to identify associated risk factors for a subtherapeutic INR (&lt;1.8) on day of discharge. The majority of patients (58.6%, 146 of 249) following TJA surgery were found to have a subtherapeutic INR level (INR&lt;1.8) at discharge (mean length of stay 2.6 days). Multivariate LR analysis found that weight greater than 180 lbs. (OR 2.08, CI 1.09, 3.98, P=0.027) was found to increase the odds of a subtherapeutic INR on day of discharge. Our results were not significant for weight 20% beyond ideal body weight, age (&gt;65y), gender, peri-operative transfusion, smoking, ESRD or autoimmune disease. A patient's body weight influences response to warfarin following TJA. An inpatient warfarin dosing nomogram that takes into account a patient's weight should be used to reduce the risk of subtherapeutic INR levels in obese TJA patients

Discrepancies in the Validity of Self-Reported Cigarette Smoking in Adults With and Without ADHD

Objective: Attention-deficit/hyperactivity disorder (ADHD) is associated with an increased smoking prevalence and impairments in executive function, which may negatively affect the validity of self-reported smoking rates. This study compares the utility of self-reported smoking with salivary cotinine in adult smokers and nonsmokers with and without ADHD. Methods: Participants (N = 82) were adult smokers and nonsmokers with and without ADHD (n = 35 ADHD and n = 47 controls) from an observational study. Odds ratios (ORs) for accuracy of self-reported smoking compared to salivary cotinine were calculated using diagnosis (ADHD vs. control), gender, age, education, employment, and number of cigarettes per day as predictors. Post-hoc analysis stratified sensitivity, specificity, and accuracy of self-reported smoking in individuals with ADHD and without ADHD. Results: The initial analysis identified education as a significant independent predictor of odds of accuracy, OR = 6.22, p = .013, after adjusting for diagnosis, gender, age, employment, and cigarettes per day. Post-hoc analysis revealed that sensitivity, specificity, and accuracy of self-reported smoking was 100% for individuals with ADHD who had more than high school education compared to those with high school or less, which was 83.3%, 45.5%, and 65.2%, respectively. Self-reported smoking of control participants with greater than a high school education had a sensitivity of 85.7%, a specificity of 91.7%, and an accuracy of 88.5%. Control participants with a high school or lower education had a sensitivity of 54.6%, a specificity of 90%, and an accuracy of 71.4% for their self-reported smoking. Conclusions: Individuals with ADHD and high school or lower education showed the lowest specificity and accuracy in their self-reported smoking, which may affect documented smoking prevalence rates. This is a secondary analysis of data collected as part of a clinical trial registered as NCT00915798 at www.clinicaltrials.gov

Assessment of Dosing and Patient Factors on the Efficacy of Warfarin Following Total Joint Replacement.

The purpose of this study was to determine the percentage of patients discharged with a subtherapeutic INR &lt;1.8 using our institutions inpatient warfarin dosing nomogram following total joint arthroplasty (TJA). We examined predisposing risk factors for a subtherapeutic discharge (INR &lt;1.8), including increased body weight, age, gender, end stage renal disease (ESRD), smoking, and peri-operative transfusion. Chart review identified 249 patients for study inclusion. Logistic regression (LR) was used to identify associated risk factors for a subtherapeutic INR (&lt;1.8) on day of discharge. The majority of patients (58.6%, 146 of 249) following TJA surgery were found to have a subtherapeutic INR level (INR&lt;1.8) at discharge (mean length of stay 2.6 days). Multivariate LR analysis found that weight greater than 180 lbs. (OR 2.08, CI 1.09, 3.98, P=0.027) was found to increase the odds of a subtherapeutic INR on day of discharge. Our results were not significant for weight 20% beyond ideal body weight, age (&gt;65y), gender, peri-operative transfusion, smoking, ESRD or autoimmune disease. A patient's body weight influences response to warfarin following TJA. An inpatient warfarin dosing nomogram that takes into account a patient's weight should be used to reduce the risk of subtherapeutic INR levels in obese TJA patients