Is prenatal exposure to triptans associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring?This population-based cohort study of 10 167 children found no associations between prenatal exposure to triptans and ADHD diagnosis or ADHD symptoms among offspring.These findings suggest that there is no increased risk of ADHD in offspring associated with prenatal exposure to triptans. Triptans are commonly used in the treatment of migraine. Prenatal exposure to triptans may be associated with adverse fetal neurodevelopment; however, there is limited information about the long-term safety of triptan use during pregnancy.To examine the association between maternal use of triptans during pregnancy and diagnosis and symptoms of attention-deficit/hyperactivity disorder (ADHD) among offspring.This study used data from the Norwegian Mother, Father and Child Cohort Study (recruitment 1999-2008), linked to national health registries. Live-born singleton children born to women with migraine before or during pregnancy were included. Two analytic samples were defined: one to assess ADHD diagnosis and one to assess ADHD symptoms. Data were analyzed from May 1 to November 30, 2021.Maternal self-report of triptan use during pregnancy. Exposed children were compared with 2 groups of unexposed children whose mothers reported migraine (1) during pregnancy and (2) before pregnancy only.An ADHD diagnosis was defined as diagnosis of hyperkinetic disorder or receipt of dispensed ADHD medication. Symptoms of ADHD at 5 years were measured by the Conners’ Parent Rating Scale, where a higher score indicates more symptoms of ADHD. Cox proportional hazards regression models and generalized linear models with inverse probability weights were used to estimate weighted hazard ratios (HRs) and standardized mean differences, respectively, with 95% CIs.The ADHD diagnosis sample comprised 10 167 children , and the ADHD symptoms sample comprised 4367 children . Children were followed up for a mean (SD) of 10.6 (2.2) years. Children with prenatal triptan exposure had no increased risk of ADHD diagnosis compared with unexposed children whose mothers had migraine during pregnancy  and compared with unexposed children whose mothers had migraine only before pregnancy . There were no differences in ADHD symptom scores between exposed and unexposed children.The findings of this study suggest that there is no increased risk of ADHD among offspring associated with prenatal exposure to triptans. This cohort study uses data from the Norwegian Mother, Father and Child Cohort Study to examine the association between maternal use of triptans during pregnancy and diagnosis and symptoms of attention-deficit/hyperactivity disorder (ADHD) among offspring. Prevalence estimates of triptan use during pregnancy among women with migraine vary between 9% and 25%.5 Many women with migraine discontinue use of triptans during pregnancy or switch to acetaminophen,7 which is in line with treatment recommendations.8 However, a substantial proportion of these women report high pain intensity.6 Moreover, untreated maternal migraine has been associated with several pregnancy complications.9Triptans are the most commonly used prescription medications for acute treatment of migraine, which is a chronic neurologic disorder characterized by moderate to severe headache in combination with other symptoms.10 Some studies found increased neurodevelopmental problems in exposed offspring compared with migraine controls, mainly among younger children.12 These associations have not been observed for preschool-aged children.13 Previous studies have mainly used parent-reported outcomes, and there is a need for research on diagnoses of neurodevelopmental problems, such as attention-deficit/hyperactivity disorder (ADHD). Attention-deficit/hyperactivity disorder is one of the most common behavioral disorders in childhood, with a worldwide prevalence of 5%.14Studies of prenatal exposure to triptans during pregnancy have not found an association with increased risks of malformations.15The aim of this study was to investigate the association between prenatal exposure to triptans and ADHD among offspring. Specifically, we aimed to investigate both ADHD diagnosis and ADHD symptoms; the latter was investigated so that we could identify children with problems who do not meet the diagnostic criteria.16 All pregnant women who could speak Norwegian were invited to participate in the study from 1999 to 2008, and for 41% of the pregnancies the women provided written consent to participate.17 The cohort includes 114 500 children, 95 200 mothers, and 75 200 fathers. An overview of all questionnaires in MoBa can be found at the Norwegian Institute of Public Health webpage.18 The present study used information from questionnaire 1 , Q3 , Q4 (sent out 6 months post partum), and Q5y (sent out when the child was 5 years old); Q2 was a questionnaire about nutrition and was not included in the study. This study was based on data file version 9, released for research in November 2015 and approved by the Regional Committees for Medical and Health Research Ethics, region South-East. The establishment of MoBa and initial data collection were based on a license from the Norwegian Data Protection Agency and approval from the Regional Committees for Medical and Health Research Ethics. The MoBa cohort is currently regulated by the Norwegian Health Registry Act. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline was followed.This study used data from the Norwegian Mother, Father and Child Cohort Study (MoBa), linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry (NPR), and the Norwegian Prescription Database using the mother’s personal identification number. eFigure 1 in the 19 The NPR contains information about diagnoses and procedures in specialist health care for individual patients from 2008.20 Diagnoses are recorded according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10).21 The Norwegian Prescription Database contains information about all prescriptions dispensed to individual patients from pharmacies in Norway starting from 2004.22 Dispensed medications are coded according to the Anatomical Therapeutic Chemical (ATC) classification system.23The Medical Birth Registry of Norway is a national health registry containing information about all births in Norway since 1967, including stillbirths and elective abortions after week 12 of pregnancy.A flowchart of the study sample selection is presented in the 23 Additional information about exposure is included in the eMethods in the Women could report use of medications during pregnancy under specific indications in 2 prenatal questionnaires (Q1 and Q3) and 1 postpartum questionnaire (Q4), including migraine (Q1), migraine or headache (Q3), and headache or other pains (Q4). Because triptans are used specifically for migraine, we included triptans reported under any indication in the questionnaires. Use of triptans was coded according to the ATC classification system (code N02CC).26 Age at time of ADHD was defined as the age at the first instance of either a recorded diagnosis of hyperkinetic disorder (ICD-10 code F90) in the NPR between 2008 and 2015 or a filled prescription of ADHD medication in the Norwegian Prescription Database  from 2004 to 2016. Children with no event were censored at the end of follow-up. For these children, we did not have the exact age at time of censoring, so their age was estimated by subtracting the birth year from the year that follow-up ended (2016). The term ADHD diagnosis used in the rest of the article refers to either a recorded diagnosis or a dispensed medication.We used both diagnosis and dispensed medication to identify children with ADHD, as has been done in previous studies.28 in Q5y. The selected items are in the areas of inattention and hyperactivity or impulsivity 30 in Q1. Satisfaction with life was measured by the 5 items of the Satisfaction With Life Scale31 in Q1. Migraine is associated with disability and reduced quality of life,33 and a previous study reported reduced life satisfaction among patients with migraine compared with healthy controls.34Covariates were identified through use of directed acyclic graphs  and by weighting unexposed children by the probability of being unexposed divided by their conditional probability of being unexposed. Estimates derived from models including IPTWs are referred to as weighted estimates. We used 95% CIs to describe the precision of our estimates, corresponding to an α of .05 for a 2-sided test.Data were analyzed from May 1 to November 30, 2021. We estimated propensity scores and calculated stabilized inverse probability of treatment weights (IPTWs) to estimate the average treatment effect.For ADHD diagnosis, Cox proportional hazards regression models with robust SEs were used to estimate crude and weighted hazard ratios (HRs) with 95% CIs. Children were followed up from birth until the first instance of ADHD (diagnosis or dispensed medication) occurring after 3 years of age or censored at the end of follow-up. Year of birth was included in the regression models. Some children died (n = 28) or emigrated (n = 105) during the follow-up period, but we do not know the dates of death or emigration. These children were therefore censored at the time of their most recent appearance in any of the registries or at the end of 2016 if they did not appear in any of the registries. We assessed the proportional hazard assumption by visually examining the hazard curves.38 Generalized linear models with robust SEs were used to estimate crude and weighted mean differences in CPRS-R(S) z scores with 95% CIs.For ADHD symptoms, we estimated censoring weights in addition to treatment weights to account for loss to follow-up because only 43.0% of mothers (4367 of 10 167) returned Q5y and completed the CPRS-R(S). The probability of being uncensored was estimated using logistic regression. Only variables with complete information were included in the censoring model. Stabilized inverse probability of censoring weights (IPCWs) were estimated and multiplied with IPTWs, resulting in a combined weight in which participants in the 5-year sample were upweighted to represent participants who were lost to follow-up.39 with 30 imputations was used to impute missing values in covariates, under the assumption of missing at random. Additional information about the imputation procedure can be found in the eMethods in the 40 was used in all analyses.Multiple imputation by chained equations41 . We also compared results based on trimmed and untrimmed weights. To examine potential exposure misclassification, we applied probabilistic bias analysis with different scenarios for sensitivity and specificity  may have more symptoms of ADHD, we restricted the analysis of ADHD symptoms to children with no missing items. To assess the robustness of our models, we included different model specifications of the IPTWs, including models with prematurity and low birth weight , models without paternal and child factors, and models with maternal ADHD symptoms, measured by the Adult ADHD Self-Report ScaleMothers were classified as having migraine before or during pregnancy in 11.2% of the pregnancies (10 167 of 90 683). Of the women with migraine during pregnancy, 86.8% (4188 of 4823) also reported migraine before pregnancy. The ADHD diagnosis sample consisted of 10 167 children (5231 boys [51.5%]) born to 8412 mothers  with migraine before or during pregnancy. The ADHD symptoms sample consisted of 4367 children (2191 boys [50.2%]) born to 3855 mothers  with migraine before or during pregnancy. In the ADHD diagnosis sample, 832 children (8.2%) were exposed to triptans during pregnancy. In the ADHD symptoms sample, 401 children (9.2%) were exposed to triptans during pregnancy. Characteristics of the samples are presented in The mean (SD) age at time of diagnosis was 8.6 (2.1) years , and children were followed up for a mean (SD) of 10.6 (2.2) years . In total, 377 of 10 167 (3.7%) children received a diagnosis of ADHD. Prenatal exposure to triptans was not associated with an increased risk of ADHD compared with unexposed children whose mothers had migraine during pregnancy  and compared with unexposed children whose mothers had migraine only before pregnancy  . The hazz score 2 or more SDs from the mean, which is considered to indicate clinically relevant problems.43 Children with ADHD had a mean (SD) CPRS-R(S) score at 5 years of 2.0 (0.8)  or between triptan-exposed children and triptan-unexposed children whose mothers had migraines only before pregnancy  (The mean (SD) CPRS-R(S) score was 1.39 (0.4) , and 5.5% of the children (241 of 4367) had a to 0.07) .Probabilistic bias analysis of nondifferential exposure misclassification showed that specificity would have to be unrealistically low to change our conclusion. In realistic scenarios, bias due to nondifferential exposure misclassification could have biased our results by 2% toward the null .15 Moreover, we used modern methods to account for potential biases from loss to follow-up, confounding, and missing data.This study has some strengths, including the prospective design and long follow-up time in MoBa, with access to detailed information about potential confounders of the association between prenatal triptan exposure and childhood ADHD. In addition, we were able to assess both ADHD diagnosis and symptoms. Including the symptom perspective is important because an additional 5% of children beyond those with a diagnosis of ADHD did not meet the full diagnostic criteria but still had symptoms of ADHD according to a review of neurodevelopment outcome measures.47 Potential misclassification also applies to the outcomes. Attention-deficit/hyperactivity disorder symptoms were reported by parents and might be associated with maternal migraine and childhood ADHD. However, the mean symptom scores corresponded well with ADHD diagnosis, given that they were measured at the mean age of 5 years and 9 years, respectively, and we observed similar results. The validity of ADHD diagnosis in the NPR has not been established, but a study from Denmark found a positive predictive value of 0.87 for ADHD diagnoses in children registered in the Danish Psychiatric Central Research Registry.48This study also has some limitations. First, misclassification of exposure may have affected the results. We expect any misclassification to be nondifferential with bias toward the null, which could have led to not detecting an actual increased risk of ADHD. If a woman reported use of multiple migraine medications and indicated use both before and during pregnancy in Q1, we assumed that she was exposed to all the reported migraine medications before and during pregnancy, even though that might not have been the case. In Q4, triptan exposure was reported retrospectively 6 months after birth, and there was no specific migraine indication mentioned in this questionnaire. Reporting of late pregnancy exposure could therefore be subject to poor recall. However, the probabilistic bias analysis showed that the specificity would have had to be very low to change our conclusion. We did not have information about dosage, and dose-dependent effects cannot be ruled out. Another limitation is that migraine was self-reported. However, according to a previous study, self-reported migraine was confirmed in 82% of pregnant women.49 This finding affects the generalizability of our results and could affect the association between prenatal exposures and childhood ADHD, according to a previous study.50 Even though we used IPCW to address loss to follow-up as recommended, there could be additional factors associated with dropout not included in the censoring model, such as migraine and ADHD. In addition, we were not able to include educational level as a factor when the IPCWs were combined with IPTWs estimated from imputed data, which is a limitation, because educational level has been found to be an important factor associated with participation in MoBa.50Second, there could be bias from self-selection and loss to follow-up in MoBa. The participation rate was 41%, and participants were less likely to be young mothers and more likely to be married or cohabiting, have a high educational level, and have a healthier lifestyle during pregnancy compared with the general population.52 A recent study using quantitative genetic modeling concluded that the association between migraines and ADHD was almost completely explained by genetic factors.53 We included 2 comparison groups with expected different migraine severity, finding no systematic differences between the groups. Moreover, we tried to account for migraine severity by using satisfaction with life as a proxy. However, this measure is not specific to migraines and may not reflect differences in migraine severity, although the unexposed groups had slightly higher mean scores than the exposed group.Third, although we took several measures to address bias from confounding by indication, this could have affected our results. Migraine severity is likely to be an important confounder; women using triptans during pregnancy are likely to have more severe migraines than women not using triptans, and migraines are heritable and associated with ADHD in children.Fourth, we had too few exposed children to be able to investigate triptan exposure by trimester or to examine specific triptans. For the same reason, we cannot rule out small effects.This cohort study found no association between prenatal triptan exposure and ADHD diagnosis or ADHD symptoms at 5 years of age. This study adds to the growing literature on the safety of triptan use during pregnancy and expands it to an important neurobehavioral outcome.


The primary goal of the present research was to examine whether therelationships that social support demonstrates with both anxiety anddepression varied between adults with and without ADD/ADHD in a Canadiansample.N ≥ 16,354). Presence of social support, diagnosisof generalized anxiety disorder (GAD), and experience of major depressiveepisodes (MDEs) were estimated in the self-report ADD/ADHD and non-ADD/ADHDgroups.Data were obtained from the 2012 Canadian Community Health Survey–MentalHealth (Although social support was negatively associated with having GAD orexperiencing an MDE, and self-report ADD/ADHD was positively associated withthese outcomes. Presence of self-report ADD/ADHD did not significantlymodify the relationships between social support and GAD or MDE.Social support may be a protective factor against symptoms of anxiety anddepression in the general Canadian population, for adults with and withoutADHD. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental psychiatricdisorder defined by impaired levels of inattention and hyperactivity–impulsivity .ResearcThe purpose of the present research was to determine how social support and ADHD predictrates of anxiety and depression in Canadians, and to compare the associations thatsocial support demonstrates with anxiety and depression in ADHD and non-ADHDpopulations.Historically, ADHD was considered a diagnosis of childhood, with the disorder beingthought to resolve during adolescence or early adulthood . HoweverADHD is associated with negative outcomes across academic, social, neuropsychological,and affective domains . Adults Humans have a profound need to connect with others to gain a sense of belonging, andto manage their behaviors around establishing and maintaining social connections. Social Adults with ADHD are variably effective in modulating how they interact with others,which in turn can have a detrimental effect on their relationships with family,friends, and colleagues . As a reAlthough anxiety disorders, depressive disorders, and ADHD are distinct classes ofdisorders with different developmental trajectories across the lifespan, thesedisorders have high rates of comorbidity and share common symptom presentations. ApproxiThe magnitude of increase in generalized anxiety disorder diagnoses among individualswith ADHD is larger than among those without ADHD: the population-wide prevalence ofan anxiety disorder among individuals with ADHD being approximately 47% ,compareIn addition to the comorbid relationship between ADHD and anxiety, ADHD anddepression are also highly comorbid. One Canadian study suggested that 31% of adultswith ADHD reported a comorbid diagnosis of a major depressive disorder, compared to12.5% of their non-ADHD peers . Adults Individuals with comorbid ADHD and anxiety and/or depression experience a lowerquality of life than those who have only anxiety or depression .Given tThere is little known regarding the role of social support as a protective factor onanxiety and depression among Canadian adults with a diagnosis of ADHD. Therefore,the present research had two goals: to determine how social support and ADHD predictrates of anxiety and depression in Canadians, and to determine whether therelationships that social support demonstrates with anxiety and depression arecontingent on whether an individual has ADHD. It was hypothesized that:H1: Based on previous research  component , 2014. Tn = 2,024) were not included in the current study. Toallow for comparison with other prevalence studies . Additionally, CCHS-MHrespondents must have answered all questions related to the covariates andpredictors, as well as provided a valid response to at least one of the twooutcomes. The minimum sample size for the current study wasN = 16,354, which represented 20,427,374 Canadians , sex, region , decile for householdincome (measured continuously from 1 to 10), education level , marital status , and race .trongly disagree) to 4(Strongly agree), and responses are summed to createthe continuous scale. Possible scores range from 10 to 40, with greaterscores indicating greater social support. The SPS-10 was found to bereliable in the current study (Cronbach’s α = .93).Perceived social support was measured using respondents’ scores on the SocialProvisions Scale, a 10-item scale validated by CCHS-MH respondents were asked about whether they had been diagnosed with anymental health conditions that had persisted for, or were expected to persistfor, 6 months or longer. In one question, respondents were asked, “Do youhave attention deficit disorder?” which was used in the current study toclassify whether they did or did not have ADHD. Responses were recoded as 0(No) or 1 (Yes) in the current study. To build the interaction term, thisvariable was multiplied by the social support measure .The 2012 CCHS-MH contained items from the World Health Organization’sComposite International Diagnostic Interview (WHO-CIDI), a standardizedinstrument used for the assessment of mental health disorders and conditionsbased on the definitions and criteria of the Diagnostic and StatisticalManual of Mental Disorders (DSM-IV). Several questions from the WHO-CIDIpertained to episodes of generalized anxiety disorder (GAD) in the previous12 months. Experiencing GAD was defined as worrying about several differentthings or having diffuse worries  in the past 12 months. This definition was used toassess whether respondents met the criteria for experiencing GAD in the yearprior to completing the CCHS-MH survey: responses were recoded as 0 (No) or1 (Yes) in the current study.Several of the questions from the WHO-CIDI from the CCHS-MH dataset alsopertained to having experienced a major depressive episode (MDE) in theprevious 12 months. An MDE was defined as a period of two or more weeks inthe past 12 months in which an individual reported experiencing one of thethree following categories of symptoms: feeling sad, empty, or depressed;losing interest in most things; or feeling discouraged about how things weregoing in their life. This definition was used to assess whether respondentsmet the criteria for experiencing an MDE in the year prior to completing theCCHS-MH survey: responses were recoded as 0 (No) or 1 (Yes) in the currentstudy.All data analysis was performed using Stata version 15 and all figures were madewith Microsoft PowerPoint. A series of hierarchical binary logistic regressionanalyses were employed to examine the associations that ADHD, social support,and their respective interactions demonstrated with either GAD or MDE. Allanalyses were weighted with a person-level weight provided by Statistics Canada,meaning that estimates from the current study could be applied to Canadians whowere between 20 and 64 years old and who were included in the sampling frame.Although logistic regression does not have an assumption of homoscedasticity,because of the non-simple random sampling approach of the CCHS-MH, HC1corrections were applied for each coefficient estimate. Finally, tests formulticollinearity revealed no substantive issues and analyses proceeded asplanned. Each model progressed in the same fashion, with two unique models beingcreated for each of the two mental health outcomes:Block 1: An outcome (GAD or MDE) was regressed onto covariates .Block 2: Social support was added to the model.Block 3: ADHD was added to the model.Block 4: The interaction term  was added to themodel.F(20) = 6.03,p < .001. In Block 2, social support was entered, andwas negatively associated with experiencing GAD in the previous year,F(1) = 116.28, p < .001. Every one-unitchange in the SPS-10 score was associated with a decreased likelihood of havingexperienced anxiety, OR = 0.86, 95% CI . At thisstage, differences were examined between respondents with the lowest score onthe SPS-10  and those with the highest score : onaverage, respondents with the lowest recorded level of social support reported a49.6% probability of experiencing GAD, compared to a 1.1% probability of GADreported by respondents with the highest recorded level of social support. In Block 3, ADHD was entered into the model,F(1) = 38.97, p < .001, and waspositively associated with GAD, with a large effect size,OR = 4.72, 95% CI . To examine if the associationbetween social support and experiencing GAD differed across individuals with andwithout ADHD, the interaction term (ADHD × SPS10) was entered in Block 4, thoughwas not statistically significant, F(1) = 0.68,p = .411. See Covariates were entered in Block 1, F(20) = 11.54, p < .001. In Block 2, socialsupport was entered and was negatively associated with experiencing an MDE inthe previous year, F(1) = 160.47, p < .001.Every one-unit increase in the SPS-10 was associated with a decrease in theprobability of experiencing depression, OR = 0.86, 95% CI. Differences were again examined between respondents with thelowest score on the SPS-10 and those with the highest score: on average,respondents with the lowest recorded level of social support reported a 62.9%probability of experiencing an MDE, compared to the 2.0% probability of MDEreported by respondents with the highest recorded level of social support. In Block 3, ADHD was entered,F(1) = 31.55, p < .001, and waspositively associated with experiencing an MDE, and with a medium effect size,OR = 3.29, 95% CI . To examine if theassociation between social support and experiencing an MDE differed acrossindividuals with and without ADHD, the interaction term between social supportand ADHD was entered in Block 4, though was not statistically significant,F(1) = 0.26, p = .612. See In Block 1, depression was regressed onto covariates,The purpose of the present research was to determine how social support and ADHDpredicted rates of anxiety and depression among Canadian adults, and to alsodetermine whether the relationship that social support had with anxiety anddepression was contingent on whether an individual has ADHD. These researchquestions were examined using CCHS-MH data. Demographic covariates were included inthe analyses to ensure that the observed effects were not accounted for by otherrelated constructs and that the observed relationships between social support,anxiety or depression, and ADD/ADHD were present with the inclusion of thesecovariates. Consistent with the literature, we observed that higher scores forsocial support were associated with lower scores for anxiety and depression , and thaThe present study assessed whether social support was associated withexperiencing GAD in the previous year. Results suggested that social supportacted as a protective factor, as greater social support was associated with adecreased likelihood of experiencing anxiety, which was supported by a 49.1%probability of experiencing GAD among those reporting low levels of socialsupport, compared to a 1.1% probability of experiencing GAD among those withhigh levels of social support. This finding is consistent with prior researchthat has indicated a relationship between perceived social support and anxiety.Results also indicated that problem anxiety was positively associated with aself-reported diagnosis of ADD/ADHD, which was consistent with the literature. In the In addition to anxiety, the present study also assessed whether social supportwas associated with experiencing a MDE in the previous year. Consistent with theliterature , resultsResults also highlighted that problem depression was positively associated with aself-reported diagnosis of ADD/ADHD, which was consistent with the literature. In the The findings of the present research show that increased levels of social supportplay a significant role in reducing the risk of experiencing anxiety anddepression, and that ADHD is a risk factor for anxiety and depression. However,the results also suggest that the relationships that social support demonstrateswith anxiety and with depression are not contingent on having an ADHD diagnosis.Therefore, these findings suggest that social support may act as a protectivefactor by reducing levels of anxiety and depression, regardless of whether aperson has been diagnosed with ADHD. This point is subtle but important – thesalutary role that social support has with both GAD and MDE is not restricted towhether an individual has an ADHD diagnosis.There are several limitations to the current study. First, ADD/ADHD was assessedusing self-report data: not all CCHS-MH respondents may have had the opportunityto be diagnosed by a health professional. Therefore, without a diagnosticinterview from the respondents, and without access to their medical files, itwas not possible to confirm the accuracy of respondents’ self-reports. This lackof verification of ADD/ADHD diagnosis may have also affected the strength of theassociations between self-reported ADD/ADHD and GAD or MDE as reported in thecurrent study. Second, there was no information available in the CCHS-MH data toidentify whether participants had received any form of treatment for ADD/ADHD:without treatment information, the researchers could not determine whethertreatment mitigated the relationships between ADD/ADHD and GAD and/or MDE.Third, information regarding subtypes of ADD/ADHD was not assessed, but may havebeen relevant, given that previous studies have found differences in patterns ofanxiety and depression between subtypes . Fourth,Although the aforementioned limitations present some degree of ambiguity ininterpreting the results, it is important to note the strengths of the currentstudy, namely its nationally representative sample of Canadians. Althoughresearchers excluded some groups from the analyses, the retained sample stilloffers a high degree of external validity that was only possible because theCCHS-MH database was accessible. Within this database, Canadians from everyprovince between the age of 20 and 64 were selected in a representativefashion.Future research would benefit from using a more comprehensive measure of ADD/ADHDthat includes classification of symptoms and presentations, rather than relyingon a self-reported diagnosis. Further, to address some of the limitations of thecurrent study, future research should include additional comorbid mental healthdisorders as covariates in the data analyses, and should focus on adolescent andsenior age groups. Another avenue for future research could include examiningthe role of negative social interactions in the relationships that an ADHDdiagnosis demonstrates with anxiety and with depression among an adultpopulation. Social problems are a common feature among children with ADHD , but theThe current study investigated the relationships between anxiety or depression andsocial support in both the (self-report) ADD/ADHD population and the non-ADD/ADHDpopulation within a Canadian context. Despite the limitations of the presentresearch, the findings suggest that social support can act as a protective factoragainst anxiety and depression, although there was no significant difference in theeffect of social support on mental health outcomes between the ADD/ADHD andnon-ADD/ADHD groups.Although it is not possible to “cure” ADHD, it is possible to alleviate its symptomsand to perhaps prevent the development of comorbidities such as anxiety anddepression. It has been suggested that the sense of well-being reported byindividuals receiving psychological treatment for ADHD is the result of relievinganhedonia and dysphoria . The posFurther, research has shown that individuals with anxious and depressive disordersrespond more strongly and positively than controls when they encounter positiveevents .The res


Because emotional symptoms are common in attention-deficit/hyperactivity disorder (ADHD) patients and associate with much morbidity, some consider it to be a core feature rather than an associated trait.Assess the possibility that symptoms of emotional dysregulation should be considered as core diagnostic feature of ADHD.It’s a cross sectional study, including 60 children with ADHD and 60 children without ADHD ranging from 6 to 19 years of age (mean age 10.43 years). We defined moderate emotional dysregulation if a child had an aggregate cut-off score of ˃180 on the Anxiety/Depression, Aggression, and Attention scales of the CBCL and severe emotionaldysregulation if a child had an aggregate cut-off score of ˃ 210. This profile was selected because of its conceptual congruence with the clinical concept of emotionaldysregulation.Sixty-three percent of children with ADHD had a severe emotional dysregulation versus 12% of controls (P˂0.001). Emotional dysregulation was associated with elevated rates of hyperactivity and impulsivity : Ninety-six percent of the children with hyperactivity-impulsivity, according to the Conners scale, had emotional dysregulation. With a significant correlation between emotional dysregulation and hyperactivity-impulsivity (p = 0.001). Also all children with attentional disorders exhibited emotional dysregulation and a significant correlation between emotional dysregulation and inattention has been found in both groups (p=0.000).Emotional dysregulation is now known to play a causal role regarding ADHD symptomatology. It should therefore be included in future theoretical models of ADHD, as well as in clinical practice when identifying the major impairments in this diagnostic group and when deciding therapeutic strategies.


Secale cereale L.). FISH analysis using these sequences as probes indicated that the signals of 1R1, 3R1, 4R1, 4R2, 5R1, 5R2, 6R1, 6R2, and 7R1 were located in the centromeric regions of rye 1R, 3R, 4R, 4R, 5R, 5R, 6R, 6R, and 7R chromosomes, respectively. In addition, for each of the centromeric single-copy sequences, high sequence similarity was observed among different Secale species. Combined with rye genomic sequence, single-copy FISH analysis indicated that the 1BL.1RS translocations in wheat cultivar CN17 and wheat line 20T363-4 contained the centromeric segment of 1R chromosome from 349,498,361 to 349,501,266 bp, and the 1BL.1RS translocations in the other two wheat cultivars did not contain this segment. The nine sequences are useful in determining the centromere location on rye chromosomes, and they have the potential to disclose the accurate structural differences of centromeres among the wheat-rye centric fusion translocation chromosomes; therefore, more centromeric single-copy sequences are needed.Single-copy FISH analysis is a useful tool to physically locate a given sequence on chromosome. Centromeric single-copy sequences can be used to locate the position of centromere and disclose the subtle differences among different centromeres. Nine centromeric single-copy sequences 1R1, 3R1, 4R1, 4R2, 5R1, 5R2, 6R2, 6R3, and 7R1 were cloned from Kustro ( Cucumis anguria and cucumber [Cytogenetic methods, such as genomic in situ hybridization (GISH) and fluorescence in situ hybridization (FISH) have been widely used to study the genome structure and evolution of plant . Among tcucumber . Moreovecucumber ,7,8,9,10cucumber ,4,7,8; hcucumber ,12,13,14cucumber . These rcucumber ,17,18. Rcucumber . To studSecale sylvestre and Secale strictum, and Primer-4R1 and Primer-7R1 amplified their target sequences from Secale strictum . The individual rye chromosome was judged by the signal pattern of the probe Oligo-pSc119.2-1. It can be noted that all the FISH signals of the nine probes were only located in the centromeric regions of their corresponding chromosomes  and two wild rye  was observed [Rapid evolution of centromeric repetitive sequences resulted in the centromere paradox . In mostobserved . These robserved . In addiobserved . In thisWheat-rye 1BL.1RS translocation was formed by the centric fusion of the short arm of rye chromosome 1R and the long arm of wheat 1B chromosome. The centromere of 1BL.1RS translocation is a good model for studying the structure and function of centromere due to its hybrid character. The structure and function of the centromere of wheat-rye 1BL.1RS translocation have already been studied ,18,24,25Secale sylvestre Host and Secale strictum (C. Presl) C. Presl (PI 531829), and six cultivated rye  including Kustro (PI 392065), Weining, Qinling, Wugong, Jingzhou, and Petkus (PI 330965), and three wheat-rye 1BL.1RS translocation cultivars AiKang 58 (AK58), Predgornia, and Chuannong 17 (CN17), and a 1BL.1RS line 20T363-4 were used in this study. PI 531829, PI 392065, and PI 330965 were kindly provided by the American Germplasm Resources Information Network (GRIN). The AK58 and Predgornia were kindly provided by Crop Research Institute, Sichuan Academy of Agricultural Sciences, China. The other materials were from our laboratory. The 1BL.1RS translocation cultivars Predgornia, CN17, and AK58 have been reported [Triticum aestivum L.) Mianyang11 × rye  Kustro [Two wild rye reported ,27,28. Tl PI 5318, and sixhttp://mcgb.uestc.edu.cn/b2dsc, accessed on 6 May 2021) [The cereal centromeric sequence CCS1  and rye ay 2021) .Secale sylvestre or Secale strictum. The PCR reaction mixture  contained 200 ng of template DNA, 3 μL of each primer with concentration of 10 μmol/L, and 42 μL 1.1 × T3 Super PCR Mix . PCR amplification was performed in a Coyote Bio PCR System  using the following program: Pre-denaturation at 98 °C for 2 min, followed by 35 cycles of denaturation at 98 °C for 10 s, annealing at 55 to 60 °C depending on each primer for 10 s, extension at 72 °C for 1 min, and final extension at 72 °C for 2 min. The amplified products were electrophoresed in a 1.5% agarose gel in 1 × TAE buffer. The target sequences were cloned into TSINGKE pClone007 vector  and sequenced by the Tsingke Biotechnology Co., Ltd. . The cloned sequences were deposited in the GenBank Database. The similarity of these sequences were analyzed using DNAMAN .Nine primer pairs were designed according to the candidate single-copy sequences from the rye Weining using Primer 3 software (version 4.0) . Some prSingle-copy FISH analysis was used to locate the single-copy sequences on rye chromosomes. The preparation of root-tip metaphase chromosomes was carried out according to the method described by Han et al. . The proND-FISH experiments were performed as described by Fu et al. . The oliIn this study, nine centromere-specific single-copy sequences of rye were found. These sequences are useful in determining the centromere location on rye chromosomes. In addition, they have the potential to disclose the accurate structural differences of centromeres among the wheat-rye centric fusion translocation chromosomes; therefore, more centromeric single-copy sequences are needed.


Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that exhibits unique neurological and behavioral characteristics. Those with ADHD often have noted impairments in motor performance and coordination, including during tasks that require force modulation. The present study provides insight into the role of altered neural processing and SMI in response to a motor learning paradigm requiring force modulation and proprioception, that previous literature has suggested to be altered in those with ADHD, which can also inform our understanding of the neurophysiology underlying sensorimotor integration (SMI) in the general population.n = 15) and neurotypical controls (n = 15) performed a novel force-matching task, where participants used their right-thumb to match a trace template that varied from 2–12% of their Abductor Pollicis Brevis maximum voluntary contraction. This motor task was completed in pre, acquisition, and post blocks. Participants also completed a retention test 24 h later. Median nerve somatosensory-evoked potentials (SEPs) were collected pre and post motor acquisition. SEPs were stimulated at two frequencies, 2.47 Hz and 4.98 Hz, and 1,000 sweeps were recorded using 64-electrode electroencephalography (EEG) at 2,048 Hz. SEP amplitude changes were normalized to each participant’s baseline values for that peak.Adults with ADHD , with improvements maintained at retention . The ADHD group had a decreased N18 post-acquisition (0.87 ± 0.48), while the control N18 increased (1.91 ± 1.43). The N30 increased in both groups, with a small increase in the ADHD group (1.03 ± 0.21) and a more pronounced increase in controls (1.15 ± 0.27).Unique neural differences between groups were found after the acquisition of a novel force-matching motor paradigm, particularly relating to the N18 peak. The N18 differences suggest that those with ADHD have reduced olivary-cerebellar-M1 inhibition when learning a novel motor task dependent on force-modulation, potentially due to difficulties integrating the afferent feedback necessary to perform the task. The results of this work provide evidence that young adults with ADHD have altered proprioceptive processing when learning a novel motor task when compared to neurotypical controls. Attention-Deficit/Hyperactivity Disorder (ADHD) is described as a neurodevelopmental disorder. The hallmark characteristics associated with ADHD are behavioral signs, such as hyperactivity, impulsivity, and inattention . These nWhile ADHD is defined by behavioral alterations, there are neurological characteristics that are important to note, and that are relevant to the current research. Those with ADHD tend to have reduced cerebral gray matter diffuse throughout the cortex . With anThe cerebellum is fundamental to the processes underlying motor learning and SMI, including playing a fundamental role in how individuals utilize feedback to refine and control motor output . As noteDespite the above advances in the understanding of how the structure of the cerebellum may be altered, it is unclear how these neural characteristics will affect processes related to motor learning and performance in adults with ADHD. Utilizing techniques such as somatosensory evoked potentials (SEPs) can provide insight on the level of neural activity within cortical and subcortical structures in response to a novel motor task. SEPs are a non-invasive neurophysiological technique that allow for the assessment of neural structures via stimulation of a peripheral nerve, and are named based on their polarity and latency . For insAlthough limited literature has addressed motor performance, at either a behavioral or neurophysiological level in adults with ADHD, those with ADHD generally experience difficulties in tasks that require motor coordination and performance . As noteWith respect to motor control, optimal performance is associated with reduced variability . TherefoMany tasks require our ability to modulate force to elicit effective performance. Force modulation depends on proprioception via sensory feedback from several sensory structures, including muscle spindles, golgi tendon organs, Pacinian corpuscles, and the cutaneous receptors of the digits . ExampleProprioception is defined as ones’ ability to use their senses to understand where their limbs and body are in space and includes the processing of somatosensory input . AlteratNeurotypical children reach peak cortical thickness by the age of 7.5 years old, whereas children with ADHD reach this milestone by approximately 10.5 years old . These mThe purpose of the current work was to assess whether young adults with ADHD exhibit alterations in neural processes related to learning a novel force-matching task (FMT). Utilizing both behavioral and neural variables allows for a multifaceted approach to form an enhanced understanding of motor learning in those with ADHD. The research question that this work aims to address is, do young adults with ADHD experience alterations to motor acquisition and learning when performing a task dependant on force modulation and proprioception? The primary neurophysiological and behavioral variables assessed were short-latency SEP peaks and performance via percent error at each phase of the motor acquisition paradigm. Specific hypotheses include: (1) those with ADHD will exhibit alterations to SEP peaks when compared to neurotypical controls, likely in peaks related to cortico-cerebellar processing; (2) those with ADHD and neurotypical controls will show performance improvements post-acquisition, and based on previous literature, those with ADHD will likely have reduced improvements at retention measures when compared to controls.Written informed consent was obtained prior to the start of data collection. This study was approved by the Ontario Tech University Research Ethics Board . This study was carried out according to the ethical standards set out by the Declaration of Helsinki statutes governing research on human subjects.f = 0.4), an alpha of p = 0.05, and a power (1-β) of 0.95 (β set at 0.05 to minimize the chance of a type II error), a sample size of 12 participants per group is needed for a pre-post experimental design  and one group of neurotypical controls . Participants completed several pre-screening questionnaires to ensure they met the inclusion criteria, including being between the ages of 18-35 years old, right-hand dominant, the absence of any other known neurological conditions, or history of injury such as concussions. Handedness was confirmed using the Edinburgh Handedness Inventory (EHI) self-report questionnaire.GPOWER statistical software indicated that for a large effect size . This was used to assess symptoms associated with ADHD in both groups. The ASRS consists of 18 questions, divided into part A and part B, these questions are in line with the ADHD diagnostic criteria set out in the DSM-IV . Each ofData collection sessions occurred over two days. All participants attended two sessions, the second being 24-48 h after the first. The first session included EEG and SEP collections, where participants completed the motor task in phases, beginning with the pre-acquisition phase and finishing with the post-acquisition phase of the force-matching task (FMT). On day one, participants completed the informed consent documents, giving both written and verbal informed consent prior to the commencement of the session. This was followed by the setup of the EEG and SEPs. Baseline SEPs measurements were then recorded, including both 2.47 Hz and 4.98 Hz stimulation frequencies. Following baseline SEPs, participants completed the novel force-matching task (FMT) in blocks of pre-acquisition (4-blocks), acquisition (12-blocks), and post-acquisition (4-blocks) as depicted in Participants were instructed to complete a novel motor task that required them to modulate the force from their right thumb in order to accurately match a waveform trace that varied in force, based upon a percentage of their individual maximal voluntary contraction (MVC) of the Abductor Pollicis Brevis (APB) muscle. Individual MVCs were determined by asking participants to apply as much force as possible onto the 50 kg force transducer, using their right thumb, while limiting any forearm, elbow, or shoulder integration . MVCs were calculated based on the average of three trials. During the force-matching task (FMT), each trace was presented on a computer monitor positioned in front of the participant. The force transducer was stabilized on a height-adjustable table to the right of the seated participant and table height was adjusted to a comfortable height for each participant.The task was created and presented with a custom LABVIEW software program . To match the traces in the program, participants had to use their right thumb to push against a force transducer with a 50 kg load cell. The trace that participants were to match as accurately as possible was a continuous trace of white dots with two red error bars acting as a guide. The error bars were placed 0.05% above and below the dotted force trace. Throughout the duration of the task, participants were presented with augmented visual feedback in the form of a yellow solid line, representative of the force they were exerting against the transducer. This provided a visual depiction of how accurately they matched the intended trace. The traces varied between 2 and 12% of each participants Abductor Pollicis Brevis (APB) MVC , with isWhen completing the task, participants were seated in a standard stationary work chair with feet flat on the floor. Their right arm and hand were pronated and resting on the table, with their right thumb to the left of the force transducer. Their forearm was strapped to the table using two Velcro straps. This was to limit the involvement of the shoulder and elbow in the task, assisting in ensuring participants were limited to using their right thumb. The task was completed in the following order: pre/baseline (4-blocks of traces), acquisition (12-blocks of traces), and post (4-blocks of traces), 24-48 h later participants returned to the lab and completed the retention (4-blocks of traces) test. Each block consisted of three to five trials, and each trial was 20 s long. Blocks, which were a series of three to five trials, were presented in a randomized order for each participant, to ensure that there was not an order effect on performance and learning.As it pertains to peripheral SEPs, recording electrodes were placed according to the International Federation of Clinical Neurophysiologists (IFCN) guidelines . SurfaceThe following SEP peaks were identified and the amplitude was recorded and analyzed at baseline and post motor acquisition. Each participant’s “post” measurement was normalized to their baseline value, allowing for an assessment of proportional change in SEP peak amplitudes following motor acquisition. The peripheral N9 and the spinal N11 and N13 were each recorded using Signal4 Software , and the following peaks were recorded using a Waveguard™ whole-head high-density 64-electrode EEG cap , including the far-field N18 (P14–N18 complex), the parietal N20 (P14–N20 complex), and P25 (N20–P25 complex), the frontal N24 (P22–N24 complex), and the frontal N30 (P22–N30 complex). Each of these SEP peaks are reflective of activity within specific neural generators .SEPs were stimulated at two different sampling frequencies, this was to allow for the clear identification of the N24 SEP peak. The 2.47 Hz frequency was used to clearly identify the N30 peak, whereas the faster stimulating frequency at 4.98 Hz results in the attenuation of the N30 SEP peak, allowing for a clear identification of the N24 peak . The sloMedian nerve SEPs were elicited via stimulation of the median nerve over the right wrist, just proximal to the distal crease of the wrist. Stimulation intensity was set at motor-threshold of the Abductor Pollicis Brevis (APB) muscle for each participant, which was observed as the lowest possible intensity where a 1 cm visible thumb twitch occurred. This motor response occurred as a result of the electrical stimulation of the median nerve, as the median nerve is a mixed-nerve. This ensured that the 1a afferents were being stimulated, which will result in the short-latency SEP peaks, due to their projection to the cerebral cortex . For the® .A Waveguard™ 64-electrode whole-head EEG cap  was used to record central SEP peaks, including the N18, N20, P25, N24, and N30. The Waveguard™ cap was connected to a TMSi REFA-8 amplifier with 64 EEG channels, four bipolar channels, and four auxiliary channels. The collection was run through asaLab™ (Netherlands), and collections were recorded at a sampling frequency of 2048 Hz . SEP anaA custom LabVIEW™ program was used to filter and analyze the force data. A 0.5 s moving average window was applied to the data for smoothing of the force signal . VariablTo calculate percent error, the following equation was used:.The SEPs signals were amplified  and filtered  on a laboratory computer . PeripheAll SEP peaks were measured from the preceding trough/peak to the following peak/trough of interest. The change in amplitude in units of μV was recorded at baseline and at post measures. SEPs peak amplitude changes were then normalized to that peak’s baseline value for each participant. This allows for an assessment of proportional change for each SEP peak. Latency in units of ms for each peak was also recorded to ensure peaks were consistently identified for each participant.To confidently say that SEP changes are not a result of peripheral changes, it is necessary to determine that the afferent input between pre and post measures was stable, to ensure any changes in central SEP peaks were a result of neural adaptations from learning and not a by-product of postural alterations, for example. This was done by ensuring stability of the N9 SEP peak over the brachial plexus/Erb’s point. The N9 had to remain stable pre-post to use the data set. Therefore, the N9 SEP peak had to be within ± 20% pre-post to include that participant’s neurophysiological data . All N9 Whole-head EEG was used to record and analyze central SEP peaks, including the N18, N20, P25, N24, and N30. Data was cleaned and any artifacts, including eyeblinks, were removed prior to running analyses. Artifacts which were a result of muscle activity and ocular activity were removed using ASA software, excluding signals that were ± 100 μV. EEG data was filtered using a band-pass filter with a low cut-off of 0.2 Hz and a high cut-off of 1,000 Hz, slope steepness was set at 24 dB/octave . Data wap ≤ 0.05 for all analyses . Effect sizes are reported using partial eta squared (η2), with a small effect as 0.01, medium as 0.06, and a large effect as 0.14  and between subject factor of group (ADHD and control) as measures was performed on both the mean percent error and the force variability (SD). This was performed on both the absolute and normalized data, as the absolute data can show differences in absolute motor performance, whereas the normalized data can show performance improvements relative to baseline as a result of learning. Behavioral data was normally distributed, with the exception of the absolute “pre” scores for both groups. Therefore, log transformations were performed on the absolute performance scores to correct for this violation of normality.p-value from the smallest value to the largest value, which is done for all SEP peaks. These values are then compared to the Benjamini-Hochberg critical value  as the repeated measure and group (ADHD and control) defined as the between subject factor for each SEP peak. All SEP peak data was normally distributed. Furthermore, the Benjamini-Hochberg test was performed to correct for multiple comparisons that are independent from one another for short-latency cortical SEP peaks . Differeal value . A giventerature . HoweverSupplementary data can be found in 2,28 = 61.645; p < 0.0001; partial η2 = 0.688) for the normalized performance scores. This shows that both groups (ADHD and control) improved from baseline to post-measures (ADHD: 0.850 ± 0.093 vs. control: 0.848 ± 0.103) and at retention compared to baseline (ADHD: 0.816 ± 0.114 vs. control: 0.825 ± 0.110). Post-hoc tests showed that pre-scores were significantly different than retention and post, while retention and post were not significantly different from one another. An effect of group was not present . Absolute mean scores: Absolute performance scores can be seen in 2,26 = 33.759; p < 0.0001; partial η2 = 0.650) for absolute performance scores. This illustrates that both groups (ADHD vs. control) improved from baseline (ADHD: 0.757 ± 0.184 vs. control: 0.696 ± 0.158) to post-measures (ADHD: 0.633 ± 0.107 vs. control: 0.578 ± 0.068) and from baseline to retention (ADHD: 0.601 ± 0.068 vs. control: 0.560 ± 0.052). Post-hoc tests showed that pre-scores were significantly different than retention and post, while retention and post were not significantly different from one another. An effect of group (ADHD vs. control) was not reached .Normalized performance scores can be seen in 2,28 = 46.446; p < 0.0001; partial η2 = 0.624) for the normalized force variability. This shows that both groups (ADHD and control) became less variable from baseline to post-measures (ADHD: 0.90 ± 0.077 vs. control: 0.89 ± 0.093) and at retention compared to baseline (ADHD: 0.85 ± 0.091 vs. control: 0.89 ± 0.093). Post-hoc tests showed that variability at pre-measures were significantly different than retention and post, while retention and post were not significantly different from one another. An effect of group was not present . Absolute variability: Absolute variability can be seen in 2,26 = 42.168; p < 0.0001; partial η2 = 0.601) for absolute variability. This illustrates that both groups (ADHD vs. control) had less variable force output from baseline (ADHD: 0.1.32 ± 0.23 vs. control: 1.22 ± 0.19) to post-measures (ADHD: 1.17 ± 0.15 vs. control: 1.07 ± 0.089) and from baseline to retention (ADHD: 1.11 ± 0.12 vs. control: 1.07 ± 0.093). Post-hoc tests showed that variability at pre-measures were significantly different than retention and post, while retention and post were not significantly different from one another. An effect of group (ADHD vs. control) was not reached , although a medium effect size was present.Normalized force variability data can be seen in 1,28 = 0.015; p = 0.903; partial η2 = 0.001) or group present . Therefore, all participants data is included in the SEP peak analysis. SEP peak data can be seen below in All participant’s SEP data was included, as the inclusion criteria of the N9 SEP peak was always met. Specifically, the N9 was recorded over the ipsilateral brachial plexus, and when comparing pre-post measures, the N9 differed by no more than ± 20% from baseline measures . This as1,28 = 3.523; p = 0.071; partial η2 = 0.112) or group were present , although a medium effect size was reached for time.No effect of time  or group were present .No effect of time , although it approached significance and a medium effect size was evident. A significant effect of group  and a time x group interaction were present . The N18 decreased in those with ADHD (0.87 ± 0.48) and increased in controls (1.91 ± 1.43).A main effect of time was not present  or group were present .No effect of time  or group were present , although a medium effect size was present when comparing between groups.No effect of time  or group were present .No effect of time  was present. The N30 increased in both groups . A main effect of group or a time by group interaction were not present . Representative traces of SEP peaks where effects were present can be seen in A significant effect of time  in a manner that differs from those in neurotypical controls. The specific SEP peaks that changed as a result of the novel force-matching task (FMT) were the N18 and the N30. The N18 SEP peak, which reflects activity within cortico-cerebellar networks, increased in the control group, yet decreased in ADHD group. In contrast, the N30 SEP peak increased in both those with and without ADHD, suggesting similar changes in each group. Additionally, both groups exhibited improvements in performance at post and retention measures, suggesting that they did indeed learn throughout the acquisition phase of the paradigm. When assessing absolute performance measures, those in the ADHD group appeared to exhibit greater error at all phases of the paradigm, when compared to controls, although this did not reach statistical significance a medium effect size was present, and may be an important topic of inquiry in the future. Therefore, the normalized performance scores suggest that both those with and without ADHD learned to a similar extent, as seen by similar proportional improvement , although absolute values may suggest reduced overall performance in those with ADHD when compared to neurotypical controls. Overall, the opposite direction of change in the N18 SEP peak neural marker following acquisition of the force-matching task, coupled with the lack of group differences in the performance of the task, suggests that adults with ADHD did learn the force task, but did so using a different pattern of neural processing.One way to infer if motor learning has occurred can be via changes in performance over time, such as improvement in accuracy or reduced variability after the acquisition of a novel skill . ThroughSEPs offer a non-invasive technique to assess cortical and sub-cortical processing between groups and in response to various tasks. Each SEP peak is reflective of activity within a specific neural structure . Due to The results from the current study showed that those with ADHD exhibited different neural processing after learning the novel force-matching task (FMT) than did controls. This difference was evident for the N18 SEP peak, where those in the ADHD group exhibited a reduction in the N18 peak amplitude after performing the motor acquisition paradigm and controls exhibited an increase in peak amplitude. This is the first study to utilize a motor acquisition task highly dependent on proprioception and force modulation in those with ADHD, in conjunction with a neural measure to assess cortical and subcortical processing. The current work is in line with previous research utilizing similar methodology in controls, which saw as an increase in the N18 SEP peak in controls after acquisition of a novel force-matching task (FMT) . The N18The cerebellum is a neural structure that plays a fundamental role in the process of learning. Particularly, the cerebellum has increased activity during the initial stages of learning . ConsequPrevious work, utilizing a 20 min repetitive typing task, found an decrease in the N18 in controls, which was suggestive of a reduction in a filtering effect prior to cortical processing during the early stages of learning . The resThe current study noted an increase in the N30 in both groups after completing the novel force-matching task (FMT). Previous work has found that motor acquisition paradigms result in an increase in the N30 SEP peak amplitude . Recent The increase in the N30 in both groups suggests increased activity in brain regions heavily involved in SMI. Therefore, the demands of the novel force-matching task (FMT) resulted in similar activation patterns in these brain regions in those both with and without ADHD. Although of relevance, a main effect of group was absent when assessing the N30, a medium effect size does suggest that there may be differences in the N30 between groups. For instance, the control group saw a mean increase in the N30 by 15% at post measures, whereas those in the ADHD group exhibited a modest mean increase of 3%. This suggests that there may be inherent differences in SMI processes in those with ADHD when completing a proprioceptive dominant motor acquisition task, such as the one utilized in the current study. Specifically, an attenuated increase in the N30 when compared to neurotypical controls. If this is the case, it may be a result of altered neural structure and function in those with ADHD, such as those in prefrontal cortical regions , affectiAlthough pre-screening did include assessing for the presence of any known neurological conditions, DCD was not directly a part of that screening. This could pose a potential limitation, as recent work has suggested motor difficulties typically associated with the ADHD phenotype may be related to a co-occurring deficit in motor abilities . The ADHThis present work is the first to assess the neural mechanisms involved in force-dependent motor learning, heavily reliant on proprioception, in young adults with ADHD. The current technique involved the assessment of short-latency SEPs and behavioral improvements via performance accuracy. Those in the ADHD group exhibited a significantly reduced N18 SEP peak when compared to neurotypical controls whose N18 increased post-motor acquisition, suggesting reduced olivary-cerebellar-M1 inhibitory activity in the ADHD group, in response to the novel motor task. This may reflect an increased reliance on proprioceptive feedback via a reduction in the filtering effect in order to perform the task, potentially as a result of difficulty in the processing and integration of the force and proprioceptive input in association with the visual feedback presented. Behaviorally this may be related to the trend for increased absolute error in the ADHD group. However, both groups showed equivalent improvement in absolute and relative performance, thus task learning did occur to a similar degree in both groups. There was also a similar increase in the N30 peak, contrasted by the opposite adaptation of the N18 peak. In the future, utilizing forms of neural assessment that provide an improved form of spatial acuity, such as those offered by source localization techniques, or fMRI if feasible, could prove beneficial in improving our comprehension of how those with ADHD learn novel motor tasks, particularly those that require a high level of force modulation acuity. Overall, this present work suggests that adults with ADHD exhibit different neural processing related to learning a force-dependent motor paradigm.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ontario Tech University Research Ethics Board. The patients/participants provided their written informed consent to participate in this study.HM, BM, UA, and PY conception and design of research. HM and UA performed the experiments. HM analyzed the data and drafted the manuscript. HM, BM, PY, and UA interpreted the results. HM, BM, PY, and CG edited and revised the manuscripts and approved the final version of the manuscript. All authors contributed to the article and approved the submitted version.


This paper reports findings regarding patterns of vaccine usage in sheep and goat farms, in 325 sheep flocks and 119 goat herds throughout Greece. The objectives of the study were (a) to describe the patterns of vaccine administration in small ruminant farms and (b) to highlight factors that were associated with vaccinations in the farms. Vaccination against brucellosis was performed in all farms into the study. Among optional vaccinations, anti-clostridial vaccination was most frequently performed (in 97.8% of farms), followed by vaccination against contagious agalactia, (56.5% of farms), pneumonia (41.2%), chlamydial abortion (38.1%), staphylococcal mastitis (36.0%), and paratuberculosis (9.5%). Vaccinations against pneumonia and staphylococcal mastitis were performed more frequently in sheep flocks, whilst vaccinations against paratuberculosis were performed more frequently in goat herds. On average, 2.8 and 2.7 optional vaccinations  were performed in sheep and goat farms, respectively. The increased number of vaccines administered was associated with a higher average milk production in the respective farms. There was an association of vaccination against staphylococcal mastitis with a reduced recovery of staphylococci from the bulk-tank raw milk. In multivariable analyses, significant associations of the administration of the various optional vaccines were seen with 15 variables, 11 related to health management practices and 4 related to the demographic characteristics of farmers; the collaboration with a veterinarian, the daily number of milking sessions, and the period spent daily by the farmer at the farm premises were each associated with the administration of vaccines against three infections. Toxoplasma gondii infection). Thus, knowledge of the patterns of vaccine administration in livestock farms can be employed to ensure that the vaccines are administered properly and that they provide a high protection in the target animals.Vaccinations have had significant beneficial effects on small ruminant health and production and are paramount components of health management programs applied in sheep and goat farms . UsuallyThere is a paucity of relevant information internationally about vaccination programs clinically applied in sheep and goat farms. Most relevant studies have focused on the importance of vaccination against brucellosis ,3,4, a dIn small ruminants, the CORE vaccination is internationally the anti-clostridial infection vaccination . HoweverDairy sheep and goat farming is the leading sector of the agricultural industry in Greece and has a large and important milk production. There are approximately 8.4 million sheep and 3.6 million goats in Greece, which represent 6.5% and 22.0% of the respective animal numbers in Europe. Milk production from these animals in total covers approximately 15% of the entire European milk production from small ruminants [Despite the importance of small ruminant farming for the food production sector in Greece, the patterns of vaccine administration in sheep and goat farms in the country have not been investigated and described. This paper reports findings regarding patterns of vaccine usage in sheep and goat farms, as found in a detailed countrywide investigation carried out in 325 sheep flocks and 119 goat herds around the country. The objectives of the study were (a) to describe the patterns of vaccine administration in sheep and goat farms and (b) to describe factors that were associated with vaccinations in the farms.We performed a cross-sectional study (April 2019–June 2020) in 325 sheep flocks and 119 goat herds. The study expanded in all the 13 administrative regions of Greece . DetailsAt the start of each visit to the farms, the accompanying veterinarians made the introductions. The objectives and the details of the study were presented to and discussed with the farmers by the senior author (G.C.F.), who then introduced the interviewer (author D.T.L.).The interview was performed using a structured detailed questionnaire. In a preliminary study, this questionnaire had been tested for validity of the content . In a prAfter completion of the interview, two milk samples (20 mL each) were collected directly from the bulk-tank of the farm by means of aseptic procedures, with the aim to perform bacteriological examinations in the samples. These were transported to the laboratory by the investigators themselves, in cool conditions (0.0 to 4.0 °C), by car, airplane, and/or boat, according to the locality of each farm.Within 24 h after sample collection, bacteriological techniques were employed for staphylococcal recovery and identification. Each sample was divided in two equal sub-samples, which were processed separately to increase sensitivity of the procedure. Full details of the techniques and procedures employed for bacterial recovery and identification have been described before ,18. DeteBiofilm formation by staphylococcal isolates obtained, was carried out by combining the results of two tests, specifically culture appearance on Congo Red agar plates and results of microplate adhesion test, as presented before by Vasileiou et al. . StaphylData were entered into Microsoft Excel  and analysed using SPSS v. 21 .Brucella melitensis) ), chlamydial abortion, clostridial infections, contagious agalactia, contagious ecthyma, foot-rot, paratuberculosis, pneumonia, staphylococcal mastitis, and Toxoplasma gondii abortion . The specific products administered in each farm and the vaccinations schedules employed were also considered, if provided by farmers. The above infections are important problems and significant causes of deaths and production losses in small ruminant farms and their control and prevention encompasses use of vaccinations. Initially, we performed basic descriptive analyses, and we obtained exact binomial confidence intervals (CIs). Results in sheep and goat farms were analysed and presented separately.Application of vaccinations against the following ten (10) infections in the farms was assessed: brucellosis  that might lead in mortality of newborns was associated with the proportion of lambs or kids that were sold for slaughter compared to the total number born in the farms, by using Pearson’s chi-squared test. The total number of vaccines applied in farms against five infections  that might lead in mortality of adult animals was associated with the annual incidence of mortality of adult animals in the farms, by using analysis of correlation.p < 0.2 in the preceding univariable analyses. Then, progressively, we removed variables from the model by using backward elimination. The likelihood ratio test was performed to assess p-value of each variable; among those found with p > 0.2, the one with the largest p was removed from the model. We repeated this procedure until we could not remove any value from the model, with p > 0.2. The variables included in the final multivariable models constructed for each outcome are detailed in In total, eight outcomes were considered, which referred to optional vaccinations: ‘vaccination against xxxx’, where xxxx = chlamydial abortion, clostridial infections, contagious agalactia, contagious ecthyma, footrot, paratuberculosis, pneumonia, or staphylococcal mastitis. Vaccination against brucellosis was not included, as this was fully regulated by the relevant decrees and official procedures. The variables evaluated for potential associations with the above outcomes are in total number of optional vaccines administered’ was considered. Variables, which were included in at least one of the final multivariable models during assessments of the eight outcomes described hereabove , the vaccine was administered in female animals maintained for replacement.T. gondii was not performed in any farm (0.0%)  farms, followed by vaccination against contagious agalactia, in 251 (56.5%) farms. In contrast, vaccination against abortion caused by m (0.0%) .p = 0.028 and 0.047, respectively). In contrast, vaccinations against paratuberculosis were performed more frequently in goat herds than in sheep flocks: 26.1% versus 3.4% (p < 0.0001). For the other vaccinations, the proportions of sheep and goat farms in which the respective vaccines were administered did not differ significantly (p > 0.15)  .p = 0.53). In 111 (25.0%) farms, at least three, and in 78 (17.6%) at least four different optional vaccinations were performed. In six (1.4%) farms, no optional vaccinations were performed.On average, 2.8 ± 0.1 optional vaccinations were performed in sheep flocks and 2.7 ± 0.1 in goat farms on average (p = 0.026), but not for the frequency of commercial products used against other infections .The specific products that were employed in the optional vaccinations are detailed in n = 416), contagious agalactia (n = 66), and staphylococcal mastitis (n = 134). These vaccines were administered most frequently to pregnant females. The assessment of these results did not show a difference in vaccination schedules applied between sheep and goat farms. Details are in For optional vaccinations, details of vaccination schedules applied in the farms were provided by > 7 farmers for clostridial infections  and goat herds . The increased number of vaccines administered was clearly associated with a higher average yearly milk production in the respective farms (p < 0.0001)  .p < 0.0001), whilst in goat herds, only a tendency for such an association was seen (p = 0.08) (p > 0.75).In sheep flocks, vaccination against contagious agalactia and/or staphylococcal mastitis was clearly associated with higher average milk production ( = 0.08) . For botp = 0.0002) and 101 (50.8%) flocks (p = 0.018), respectively. Of the 34 goat herds in which vaccination against mastitis was applied, they were recovered from bulk-tank milk samples from 13 (38.2%) and 9 (26.5%) herds, respectively, whilst of the 85 unvaccinated herds, they were recovered from samples from 62 (72.9%) (p = 0.0004) and 46 (54.2%) herds (p = 0.006), respectively  and 47 (37.3%) flocks, respectively, whilst of the 199 unvaccinated flocks, they were recovered from samples from 142 (71.4%) (ectively .p < 0.0001). However, no such difference was seen in goat herds: 58.2% (95% Cis: 57.3–59.1%) versus 59.3% (95% Cis: 58.6–60.0%) (p = 0.09) , in sheep farms, there was a clear association between vaccinations performed against those infections and the proportion of newborn lambs that were sold: 66.4% (95% CIs: 66.0–66.8%) in flocks where both vaccines were used versus 65.0% (95% CIs: 64.6–65.4%) in flocks where no vaccination or only one vaccine was used ( = 0.09) .p = 0.0007). However, no such difference was seen in sheep flocks: 5.32% (95% CIs: 5.14–5.50%) versus 5.15% (95% CIs: 4.96–5.37%), respectively (p = 0.23) , in goat farms, there was a clear association between the total number of vaccines administered against those infections and the annual incidence rate of mortality of adult animals: 6.30% (95% CIs: 5.94–6.68%) in herds where up to two vaccines were used versus 5.33% (95% CIs: 4.94–5.75%) in herds where at least three vaccines were used ( = 0.23) .The full results of the univariable analyses performed for the assessment of possible associations of predictors with optional vaccination against chlamydial abortion, clostridial infections, contagious agalactia, contagious ecthyma, foot-rot, paratuberculosis, pneumonia, and staphylococcal mastitis, are in Overall, in the multivariable analyses, we found significance for seven outcomes in relation to sheep flocks and for five outcomes in relation to goat herds. Of the 15 variables that were found cumulatively with a significant association with the totality of the various outcomes assessed (12 in sheep flocks and 10 in goat herds), 11 were related to health management practices performed in the farms and four to the demographic characteristics of farmers . Specifically, the collaboration with a veterinarian, the daily number of milking sessions, and the period spent daily by the farmer at the farm premises were each associated with three outcomes; another six variables  were each associated with two outcomes. The findings of the multivariable analyses are summarized in p = 0.002) (p = 0.019) (p = 0.013) (p = 0.004)   and stap= 0.019) . In goat= 0.013)  and cont= 0.004) . In thes= 0.004) .p < 0.03), whilst in goat herds, only one variable was found with a significance (p = 0.036). The results of the analyses are shown in The full results of the univariable analyses performed for the assessment of possible associations of predictors with the sum of optional vaccinations are in p < 0.01)  .Sheep and goat farming is currently the stronger branch of animal production industry in Greece, making approximately 18% of the total income of the primary sector income . In overIn this work, we studied the patterns of vaccination programs applied in 444 small ruminant farms (325 sheep flocks and 119 goat herds) during an extensive countrywide investigation. During the study, we also assessed potential associations with health-related procedures and practices and the human resources available on the farms. We included farms from all the administrative regions of Greece into the study, by means of which, situations and conditions prevailing in all areas of the country were considered and thus factors of regional importance did not play a predominant role. As far as we are aware, this was the largest sample size employed ever, as reported in the international literature, to investigate the present topic. Whilst the significance of applying correct vaccinations schemes is widely recognised, there is a paucity of detailed information and, moreover, data regarding the patterns of usage of compulsory vaccines, e.g., against brucellosis, have been mainly published.According to data sourced from the Hellenic Milk Board , the farFurthermore, our approach allowed the inclusion of flocks and herds with farmers genuinely willing to participate in the study and to provide thoughtful and correct answers. A degree of stratification was employed in the selection of farms, as the flocks and herds visited were located in all 13 administrations of the country. Whilst the general limitations of questionnaire surveys applied in this work  , we madeFirst, it is paramount to comment that the compulsory vaccination against brucellosis was reportedly performed in all the farms into the study. In the 10 last years, the Ministry of Rural Development and Food of the country has allocated significant resources for correct implementation of this vaccination in the country, with the aim to minimise cases of the infection in people . As a reWith regard to optional vaccinations, anti-clostridial vaccination, which is the CORE vaccination in small ruminants , was, asOther vaccines used in several of the farms visited over 35% of them) were the vaccines against contagious agalactia, pneumonia, chlamydial abortion, and staphylococcal mastitis. These infections are prevalent clinical problems of small ruminants in Greece ,33,34,35% of themT. gondii infections in small ruminants in Greece and the widespread cases of abortions caused by this pathogen [The significantly higher vaccination rate against paratuberculosis among goat herds than sheep flocks reflects the higher susceptibility of goats than sheep to the causal pathogen ,37. The pathogen ,39, alsopathogen , issues Vaccinations were clearly associated with improved health and production outcomes. First, the total number of vaccines was found to be associated with a higher milk production in the respective farms. This can indicate a direct beneficial effect of the vaccinations in the health of the animals in the farm, by protecting against more infections, which has resulted in a higher milk production. However, it is more likely that it reflects farmers generally more attentive to their business and applying improved management in all its facets, including nutrition, infrastructure , number of daily milkings, breed of animals, characteristics of farmers , etc., as well as vaccinations; hence, the higher milk production is the consequence of the high level of management, part of which is the higher number of vaccinations. Thus, the association between the increased number of vaccinations and the higher milk production is more likely a spurious one, rather than one indicating causation.Mannheimia haemolytica, streptococci, etc.,) [Vaccination against staphylococcal mastitis was found to be associated with the reduced recovery of staphylococci and biofilm-forming staphylococci in the bulk-tank milk. However, in previous studies, no beneficial effects have been found in quality parameters of the milk, specifically, somatic cell counts, total bacterial counts, and chemical composition ,20,41. V, etc.,) ,42, agai, etc.,) ,44. The , etc.,) .Mycoplasma agalactiae is transmitted through the milking machine teatcups during milking [Most of the variables identified with association to the administration of a vaccine are related to factors that facilitate the administration of the vaccines. For example, the increased daily presence of farmers in their business allows more time available for performing essential tasks, among them vaccinations; in another context, in farms where three milking sessions are applied daily, animals are gathered in the milking parlour more frequently and thus can be vaccinated more easily. The management system applied in farms can be related to both the feasibility of administration of vaccines , and also to the increased infectivity of some pathogens .Other variables found to be associated with the vaccinations can refer to various facets of health management in farms. For example, the average age of culling female animals can be related to the value of female animals; an early culling age of ewes does reflect a shorter production life-span of these animals, which thus need to be protected to prevent infections during that period. Moreover, the use of laboratory diagnostic examinations in samples of milk  may indicate the interest of farmers το maximise and monitor milk production in their farms.The regular collaboration with a veterinarian facilitates the design and implementation of health management plans, part of which are the vaccinations . MoreoveThe age of the farmer emerged as the most significant variable for the total number of vaccinations performed. In this respect, it is worth citing that Tauer  reportedThe breed of animals was found to be associated with the administration of some optional vaccines. It has been well-established that the animal breed can play a role in an increased susceptibility or resistance of animals to some infections, for example mastitis ,50, the The study explored the vaccination patterns in small ruminant farms. Vaccinations have contributed to controlling many major infectious diseases, despite the misinformation and the unsubstantiated resistance to their use. The correct implementation of vaccination programs, based on sound scientific principles and full compliance with established regulations and policies, are important for the improvement of the welfare of farm animals. Although most sheep and goat farms function at a low technological level, these species are important livestock animals in the agricultural industry in Greece. Moreover, as the use of vaccines would contribute to decreasing the incidence of the various infections and potentially the use of antibiotics in the farms.In dairy sheep and goats, many of the optional vaccinations scheduled in the farms are carried out during the dry-period, at the end of gestation, because they aim to protect the newborn lambs and kids , as well as the adult animals against mammary infections, given the importance of the mammary glands in those production systems . However, the dry-period in ewes and does is frequently of a short duration, often only up to two-months long; this is a rather short period for accommodating four or five vaccinations with two- to three-week intervals. This, first, creates management problems, as animals are stressed during the last stage of gestation due to the frequent handlings; moreover, it may also raise some concerns regarding the development of efficient immunity after repeated vaccinations. Further work in this area will be valuable and will help the development of effective vaccination schedules in dairy production systems.


Bartonella spp.  and typhus group rickettsiae . Bartonella quintana DNA was detected in 17.1% (14/82) body louse pools and 0.9% (1/114) blood samples. Clinicians should consider vectorborne agents as potential causes of febrile syndromes in this population.Persons experiencing homelessness in São Paulo, Brazil, were seropositive for  Bartonella and Rickettsia, particularly the louseborne pathogens B. quintana and R. prowazekii, are agents of emerging illnesses among persons who are marginalized or experiencing homelessness  by using indirect immunofluorescence assays (IFAs). In addition, we assessed risk factors related to serologic status.Persons experiencing homelessness might be predisposed to vectorborne infections because of increased exposure to ectoparasites  from a day-shelter in the city of São Paulo signed written informed consent forms and participated in this study, which was approved by the National Ethics Committee in Human Research (protocol no. 80099017.3.0000.0102). Persons responded to a questionnaire that, combined with medical and demographic records , we usedBartonella spp. and TGR. We used commercial slides for B. quintana  and in-house slides for B. henselae sequence type 9, B. machadoae 56A, R. typhi Galveston, and R. prowazekii Breinl strains. We found 79/109  persons were seropositive for Bartonella spp. and 40/109  were seropositive for TGR (titers >64). All antibody titers were >128 (B. quintana–positive and 8 TGR-positive samples. An endpoint titer >4-fold higher for a particular Bartonella/Rickettsia spp. antigen than that observed for other Bartonella/Rickettsia spp. antigens was considered the possible antigen involved in a homologous reaction (PAIHR)  persons, R. typhi was the PAIHR in 13/40  persons, and R. prowazekii was the PAIHR in 3/40  persons  for 114 blood samples and guanidine isothiocyanate and phenol/chloroform technique (Bartonella spp. by PCR of citrate synthase (gltA) and β subunit of RNA polymerase (rpoB) genes and for Rickettsia spp. by PCR of rickettsial 17-kDa antigen gene, as previously described  louse pools and 1/114  blood samples were positive for gltA and rpoB but negative for Rickettsia spp.  by BLASTn analysis (https://blast.ncbi.nlm.nih.gov). B. quintana sequences generated in this study were deposited in GenBank (accession nos. ON808843 and ON808844). The person whose blood was PCR-positive for B. quintana was not infested with body lice but demonstrated high levels of IgG against B. quintana  and TGR .Amplicons were purified and sequenced at the University of Texas Medical Branch . The https://www.r-project.org) for all statistical analyses and summarized the final conditional logistic regression model . The final TGR model contained 5 variables of which 3 were associated with higher seropositivity risk, including self-identifying as white , syphilis seropositivity , and homelessness because of unemployment . We detected 5 variables for combined Bartonella spp. and TGR of which 4 variables were associated with seropositivity, including self-identifying as white , monthly change of clothes , homelessness because of family conflicts , and higher total plasma protein .We chose risk factor variables by using unconditional logistic regression models (p<0.25) and conditional logistic regression to determine relationships between putative risk factors and serologic status. We used Bayesian information criteria to assess the goodness-of-fit for the models. We used R software version 4.1.2  was higher in our study than previous reports for persons experiencing homelessness (1.8%–65%)  and Japan   was within the range observed in the United States, Europe, and Colombia (0.54%–56.2%)  might be from a skewed population sampling, our findings should be further investigated. Nonetheless, higher TGR seropositivity was associated with homelessness because of unemployment, duration of homelessness, and syphilis seropositivity, which represent risk factors that reflect vulnerability and socioeconomic conditions. In addition, seropositivity for both Bartonella and TGR was associated with infrequent changes of clothing.Through logistic regression, we showed seropositivity for Bartonella seroreactivity with other variables included in our questionnaire, such as alcoholism, tobacco or intravenous drug use, and homelessness as previously reported (Bartonella and TGR infections (The first limitation of our study is that the small sample size and power for the examined variables might have weakened associations of Bartonella and TGR species. Clinicians should also consider these vectorborne agents as probable etiologic agents of febrile syndromes in this vulnerable population.Our results should alert public health professionals in the city of São Paulo to initiate preemptive measures and active vector control among persons experiencing homelessness and confirm circulation of Bartonella spp. and typhus group rickettsiae among persons experiencing homelessness in São Paulo, Brazil.Additional information for