The present study aimed to compare the differences in positive screening rates of attention deficit hyperactivity disorder (ADHD) symptoms between parents and teachers in the same sample of primary school students. Concurrently, parental awareness and information sources of ADHD were investigated, and possible relevant factors affecting parental awareness and their influence on positive screening rate of ADHD were analyzed.A cross-sectional study was conducted in Changchun, China, between September 2020 and January 2021. Parents of 1,118 primary school students and 24 head teachers were recruited in the survey. Data were collected through a structured self-administered questionnaire. It consisted of socio-demographic characteristics, ADHD symptom screening questionnaire, parental awareness, and information sources of ADHD.Among the 1,118 primary school students, 30 (2.7%) and 60 (5.4%) students were positive for Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) screening in the parent version and teacher version, respectively. Parents had lower positive screening rates for ADHD symptoms than teachers. Relationship with children , bachelor degree or above of parents , children’s sex , and age , children’s grade , information sources of ADHD  were the factors related to the parental awareness of ADHD.Parents and teachers of primary school students recognize ADHD symptoms differently. The positive screening rate of ADHD among teachers was significantly higher than that of parents. Relationship with children, educational level of parents, children’s sex, age, and grade, and information sources of ADHD are the relevant factors affecting parental awareness of ADHD. More efforts should be made to disseminate ADHD knowledge through mass media, and medical staff. Fathers, parents with low educational level, and parents of grade 2 and 3 pupils should be encouraged to acquire more knowledge on ADHD to improve the early recognition rate of ADHD symptoms.http://www.chictr.org.cn/showproj.aspx?proj=54 072], identifier [ChiCTR2000033388].[ Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by persistent and pervasive problems with inattention, hyperactivity, and impulsivity . ADHD usThe global estimate of ADHD prevalence is 7.2% in children and 2.5% in adults . A meta-The diagnosis and treatment of ADHD require close cooperation among doctors, teachers, and parents. The evaluation of children’s behavior by teachers and parents directly affects doctors’ judgment of children’s symptoms. Early identification of ADHD symptoms by parents and teachers can shorten the time from symptom onset to diagnosis of ADHD, contributing to early intervention and thus improving prognosis . HoweverThese inconsistencies may be related to the differences in the knowledge, understanding, and awareness of ADHD between parents and teachers. Particularly, parents’ insufficient awareness of ADHD makes it difficult for children to complete the entire assessment and treatment process at an early stage. Lack of awareness of ADHD leads to delay in recognizing ADHD and seeking appropriate treatment, which will lead to greater psychosocial problems . TherefoIn view of the problem and importance of early detection for effective treatment, this study aimed to assess and compare the differences in positive screening rates for ADHD symptoms between parents and teachers in the same sample of primary school students. Additionally, different from previous studies, parental awareness and information sources of ADHD were also investigated, and possible relevant factors affecting parental awareness and their influence on positive screening rate of ADHD were analyzed. Based on the differences in the assessment of ADHD symptoms by parents and teachers mentioned in the literature above, and the possibility that a lack of awareness of ADHD may lead to delayed diagnosis and treatment, we propose the following hypothesis: (A) Parents and teachers have different rates of positive screening for ADHD, and teachers have a higher rate of positive screening for ADHD. (B) Parental awareness of ADHD is influenced by education level and information sources of ADHD. (C) The higher the parental awareness of ADHD, the higher the positive screening rate of ADHD.This study will provide evidence for early screening and diagnosis of ADHD, provide a reference for pediatricians to make a comprehensive clinical judgment and provide important details for future ADHD-related training programs.This study was a cross-sectional study and formed part of a nationwide survey of ADHD in primary schools of urban areas in China through the “Take Care of the Mental Health of the Youth” project. The study was conducted in two key and non-key primary schools in Changchun, China, between September 2020 and January 2021. The study protocol (2020-352) was reviewed and approved by the Research Ethics Committee of The First Hospital of Jilin University . This study is registered in the Chinese Clinical Trial Registry (ChiCTR2000033388).Firstly, Changchun is a provincial capital city with a population of more than 10 million, located in northeast China. It is also one of the 13 cities in the multi-center survey of primary school ADHD in urban areas of China .Secondly, a stratified two-stage cluster sampling technique was used. First, primary schools in the city zone provided by the Youth Digest Magazine were stratified by type of school into key and non-key schools. Thereafter, two key and non-key primary schools were selected through random sampling, keeping the principle of voluntary participations, which was to say, if the randomly selected schools were not willing to participate in the study, then the voluntary schools would be included automatically. In the random selection, we put all the alternative schools in order and assigned sequence labels. We used the computer to write a random number generation program math.random. Each time we selected a sample, we used this program to randomly generate two numbers as a basis for selection. Subsequently, one class was randomly selected from each grade in each school, and 24 classes were selected in the study. Similarly, we sorted the classes for each grade and assigned sequence labels. Then we used the random number generation function to randomly generate one number each time to ensure the randomness of sample selection. The head teachers of the selected classes, and the parents of the classes eventually participated in the study.The sample size of primary school students in this center was 1,118, which met the requirements of the national sample size calculation for each center: In the multi-center survey of ADHD primary school in urban areas in China, a sample size of 4,136 was required to detect ADHD with a positive rate of 7.2% and a 95% confidence interval (CI) of 1.6%. We assumed a 70% response rate. The sample size should be increased by half due to the group sampling method in this study. Therefore, 8,863 participants were required for the multi-center study. In order to increase the representativeness of the data, four schools were selected from each of the 13 cities. As a result, six classes were selected from each school, and a total of 312 classes were selected nationwide. In China, primary schools have at least 30 students in each class, so the final sample size is at least 9,360. The sample size of each center should be more than 720 cases.The inclusion criteria included (1) acceptance and consent by parents and head teachers to participate in the study and (2) particularly for head teachers, a duration of at least 1 month as a head teacher for a class. If parents did not live with the child or were not proficient in Chinese, they were excluded from the study. Ultimately, 1,118 primary school students, their parents, and 24 head teachers were enrolled in the study.The data were collected using a structured self-administered questionnaire adapted from different literature. It consisted of socio-demographic characteristics, ADHD symptom screening questionnaire, parental awareness of ADHD, and information sources of ADHD.The parents provided information on their relationship with children, age, time spent with the child each week, level of education, household per capita monthly income level, and child’s grade. The head teachers provided information on their age, sex, and years of teaching experience, title of their technical post, training on ADHD, and experience of teaching a child with ADHD.The Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) was used in this study to screen ADHD symptoms. SNAP-IV is an unstructured questionnaire on behavior completed by a child’s parent and teacher . It consParents and head teachers completed the parent and teacher versions of the SNAP-IV rating scale, respectively, for each child. Thereafter, the positive screening rate of both versions of the SNAP-IV scale were calculated. A positive screening on the SNAP-IV Rating scale  was defiThis part of the questionnaire was used to assess the parental awareness of ADHD . These items were compiled based on a review of the literature .Each item was rated on a two-point  or was graded according to the degree of ADHD knowledge, with a rating of 0 denoting “not at all,” 1 denoting “just a little,” 2 denoting “quite a bit,” and 3 denoting “very much.” The total score was 47 points; a higher score indicated a better parental awareness of ADHD. The content reliability and validity of this part was approved by expert child and adolescent psychiatrists.These questions assessed potential sources of information on ADHD, such as medical staff, family member, relative, friend, school teachers, mass media programs about ADHD, internet, books or articles about ADHD, and leaflets about ADHD. Only two options were available as answers to these questions: yes and no.Two specific questionnaires were developed for this study: one for the parents of 1,118 primary school students enrolled in the study and the other for the 24 head teachers. A link to the questionnaire was sent to the parents through QR codes. Parents provided informed consent digitally, and completed the questionnaire. After obtaining the informed consent of parents, the 24 head teachers completed the teacher version of the SNAP-IV scale for each child in the class and questionnaire on their socio-demographic information. Finally, responses from the questionnaires were recovered through the electronic platform.t-test or a non-parametric Mann–Whitney U-test was used to compare continuous data of both groups. A chi-squared test was conducted to test the variation in the proportion of categorical variables among both groups. Parameters with P < 0.05 in univariable analysis between parents with good and poor awareness of ADHD and suspected correlation variables reported in previous literature were further assessed by multivariable logistic regression to analyze the correlation factors of parental awareness of ADHD. For the samples whose questionnaire content was obviously untrue or 90% of the questionnaire content was not completed, the data will be eliminated during the data analysis. P < 0.05 (two-sided) was considered statistically significant.SPSS v22.0  was used for all analyses. The Kolmogorov–Smirnov test was used to evaluate the normality of the data distribution. Continuous data were presented as mean ± SD, median percentile (P50), P25, or P75, whereas categorical data were presented as frequencies with percentages. According to the distribution of the analyzed variable, an independent-sample n = 1,118) completed the parent version of SNAP-IV, and 24 head teachers also completed the teacher version of SNAP-IV. The socio-demographic characteristics of the parents and students participating in this study are shown in Parents of all enrolled primary school students .Among the 1,118 primary school students, 30 (2.7%) students screened positive on the parent version of SNAP-IV, and 60 (5.4%) students screened positive on the teacher version of SNAP-IV. Parents had lower positive screening rates for ADHD symptoms than teachers  students were screened negative by parents but positive by teachers. Twenty (2.1%) students were screened negative by teachers but positive by their parents; seven (0.6%) students were screened positive by both parents and teachers. The total number of parents and teachers who provided positive screening was 76, and the total positive screening rate was 6.8%.No significant differences were found in the average age, sex, and grade composition between the students in the positive parent screening group and the positive teacher screening group . The SNAP = 0.053). The positive screening rate in the inattention and hyperactivity/impulsivity dimensions in the parent screening group was lower than that in the teacher screening group . This finding indicated that teachers had a higher ability to identify hyperactivity and impulsivity symptoms, although the differences were not statistically significant , 933 parents were divided into good awareness group  and poor awareness group . Parents’ socio-demographic data and ADHD information source of the two groups are listed in P = 0.233), although the difference was not statistically significant.The parents of all 1,118 primary school students participated in the survey of ADHD awareness and information sources of ADHD, but 185 of them were excluded due to incomplete responses to the questionnaires. With the median score of the ADHD awareness questionnaire as cut-off point , educational level of parents at the bachelor’s degree or higher level, sex and age of the child, children’s grade and ADHD information obtained from medical staff, family/relatives/friends, and TV or internet were the relevant factors that were associated with parental awareness level of ADHD .This study elicited three main findings. First, a significant difference existed between teachers and parents in the positive screening rate of ADHD symptoms in primary school students, and the positive screening rate of teachers was significantly higher than that of the parents, this is consistent with our first hypothesis. Second, teachers scored higher on hyperactivity and impulsivity symptoms than parents, and the recognition rate of these symptoms showed an upward trend. Third, relationship with children, educational level of parents, children’s sex, age, grade, and parental information sources about ADHD were the factors related to the parental awareness of ADHD.Children are often unable to reliably report their own behaviors. An ADHD diagnosis requires not only an examination of the child but also interviews with parents and data from teachers about the child’s behavior at school . TherefoKnowledge of ADHD has a positive correlation with perception of ADHD . TherefoIn addition, consistent with Interestingly, parents of girls were more aware of ADHD than parents of boys, and no study has reported similar findings. This finding seems to be contrary to conventional understanding. Compared with boys with ADHD, girls with ADHD are less likely to be referred for clinical assessments due to a lower prevalence of externalizing symptoms . HoweverAdditionally, this study revealed that the higher the proportion of ADHD information obtained from medical staff, family or friends, TV or internet, the higher the awareness of ADHD. This finding reveals that these are the main sources for parents to acquire knowledge on ADHD. Comparable results were reported by This study had some limitations. First, we only compared the positive screening rate of ADHD between parents and teachers, and did not make further diagnosis of ADHD for children with positive screening. Second, since only few head teachers participated in the study, the influence of the differences in awareness of ADHD between parents and teachers on the positive screening rate was not compared. Third, although the content reliability of the parent ADHD awareness questionnaire was endorsed by child and adolescent psychiatrists, its reliability was not verified in our sample. Fourth, sampling was only performed in the urban area of Changchun, and no investigation was conducted on ADHD of rural children, which limited the generalizability of the current findings. Future studies should expand the study population to include children in rural areas. Fifth, this study was a cross-sectional survey; therefore, causal relations could not be established. Likewise, if subsequent training had been provided, another survey could have been conducted to assess the change in knowledge on ADHD. Therefore, future psychoeducational programs on ADHD with much more advanced approaches are still needed.Recognition of ADHD symptoms among parents and teachers of primary school students differed. The positive screening rate of ADHD among teachers was significantly higher than that of parents. Teachers have higher rates of recognition of hyperactivity and impulsivity symptoms. Relationship with children, educational level of parents, children’s sex, age, and grade, and information sources of ADHD were the relevant factors affecting parental awareness of ADHD. More effort should be made to disseminate ADHD knowledge through mass media, and medical staff. Fathers, parents with low educational level, and parents of primary school students in grade 2 and 3 should be encouraged to actively acquire knowledge on ADHD to hopefully improve the early recognition rate of ADHD symptoms.The original contributions presented in this study are included in this article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Research Ethics Committee of The First Hospital of Jilin University. Written informed consent to participate in this study was provided by the participants or their legal guardian/next of kin.F-YJ and H-HL designed the work. H-HL collected and analyzed the data, and drafted the manuscript. T-TW, H-YD, and Y-QL collected the data and revised the manuscript. F-YJ contributed to the concept of this study and revised the manuscript. All authors contributed to the article and approved the submitted version.


Attention deficit hyperactivity (ADHD) disorder is a common childhood neurodevelopmental disorder, and Methylphenidate (MPH) is a first-line therapeutic option for treating ADHD.However, how brain complexity and entropy changes with methylphenidate treatment the clinical implications of possible changes in entropy and the clinical implications of possible changes in entropy have yet to be studied.This study aimed to reveal how the MPH treatment affects the complexity in the brain of children with ADHD by entropy-based qEEG analysis. In addition, the presence of the relationship between possible neurophysiological changes to be detected with clinical variables and how they are two other important questions of this study to be answered.During eyes-open resting, EEG signals were recorded from 25 boys with ADHD-combined type before MPH administration and at the end of the 1st month of the treatment. Approximate entropy (ApEn), sample entropy (SampEn), permutation entropy (PermEn) were used to analyse.A statistically significant decrease in entropy level was found with MPH treatment in the F4 channel according to approximate entropy (ApEn) and sample entropy (SampEn) analysis (p<0.05). In addition, according to permutation entropy (PermEn) analysis, the decrease in entropy with MPH treatment in the regions indicated by F3, F4, P4, T3, T6, and O2 channels was found to be statistically significant (p <0.05).This is the first study to investigate how MPH treatment affects the complexity in the brain of children with ADHD. Entropy-based qEEG analysis may be a new method that can be used in diagnostic, clinical and prognostic predictions in ADHD.No significant relationships.


The British Association for Psychopharmacology course on child and adolescentpsychopharmacology has been run for more than 20 years and is currently a verypopular course, attracting around 140 delegates/year from across the UnitedKingdom and abroad. As Faculty of recent sessions of the course, we haveselected the most common questions we have been asked in recent years andprovided evidence-based and/or expert-informed answers. We have included 27questions and answers related to attention-deficit/hyperactivity disorder,anxiety and depressive disorders, autism spectrum disorder, bipolar disorder,eating disorders, epilepsy , obsessive-compulsive disorder, personality disorders,psychotic spectrum disorders, and tics/Tourette syndrome in children and youngpeople. We hope that this article will be helpful for prescribers in their dailyclinical practice and we look forward to further, high-level evidence informingthe answers to these and other questions in child and adolescentpsychopharmacology. Accordingly, we haveindicated the mode of action when we first mention a medication. For ease ofreading, we have however used the former, traditional terminology in the remainingparts of the text.Since 2001, the British Association for Psychopharmacology (BAP) has run a course on child and adolescent psychopharmacology, that has becomemore and more popular over the years and has attracted prescribers (around 140/year)from across the United Kingdom and abroad. As Faculty of the recent sessions of thecourse, we have reported here the most frequent practical questions that we havebeen asked by the delegates, and our answers. In general, the questions were relatedto aspects/topics for which there is not a solid evidence base yet. Therefore, ouranswers reflect the available evidence alongside our clinical expertise and expertopinion. We have grouped the questions and answers by disorder to which they refer,in alphabetical order. In writing this article we have adhered to theNeuroscience-based Nomenclature (NbN), a version of which (NbN C&A) is availablealso for child and adolescent psychopharmacology . The NbNand the BNF recommended dose is 70 mg/day.The maximum recommended doses of psychostimulants  for the treatment of attention-deficit/ hyperactivity disorder (ADHD)in guidelines or formularies may be higher than the maximum licensed doses byregulatory agencies such the Food and Drug Administration (FDA) or the EuropeanAgency. More specifically, the maximum licensed dose of methylphenidate forchildren  is 60 mg/day, while the British National formulary (BNF)  recommenMany prescribers will use doses above the maximum licensed ones. Some of themwill also use doses beyond the maximum recommended in guidelines/formularies.Currently, there is no solid, meta-analytic evidence to inform if, and to whatextent, doses beyond the recommended ones are safe and bring additionalefficacy/effectiveness. Some experts agree that, while it should not be astandard, routine practice, using doses beyond the maximum recommended onescould be considered when the patient has presented with a partial response,there is only some degree of improvement at the maximum recommended dose,tolerability is good, and the aim is to optimise the response .This coFollowing poor response to two psychostimulants , some clinicians wouldconsider second- or third-line approved compounds, unlicensed medications forADHD, or combinations of different agents. However, a number of factors shouldbe assessed before switching to alternative medications or using polypharmacy.Indeed, it should be highlighted that the majority of patients with ADHD respondto one or both classes of psychostimulants, when used properly. A comparativereview of randoOnly after all these aspects have been assessed, the prescriber should consider:(1) second-line medications ; (2) augmenting agents (guanfacine or clonidine XR); (3)other agents, under specialistic advice/supervision, for which RCTs providepreliminary evidence of efficacy  .The evidence on the effectiveness of psychostimulants in marijuana users and thetolerability of the combination psychostimulants–marijuana is limited. In a RCTof OROS-methylphenidate and cognitive behavioural therapy (CBT) in youths withsubstance use disorder (in the majority of the cases (66%), marijuana), therewere no significant differences, in terms of efficacy, between participantsassigned to OROS-methylphenidate plus CBT and those in the placebo plus CBT,when considering the primary outcome (scores on the ADHD-RS completed by theclinicians), even though ADHD-RS scores rated by parents were significantlylower in adolescents treated with OROS-MPH + CBT compared to those in theplacebo + CBT arm at 8 and 16 weeks. The tolerability of OROS-methylphenidatewas not substantially different compared to what it would be expected withOROS-methylphenidate alone . AnotherIt should be noted that a subgroup of youths who use marijuana also tend tomisuse other illicit substances, which may further impact on the tolerability ofpsychostimulants. Therefore, prescribers should comprehensively screen for theuse of a variety of illicit drugs.National Institute for health and Care Excellence (NICE) guidelines currentlyrecommend CBT as a first-line treatment for moderate-to-severe depression,fluoxetine, a selective serotonin reuptake inhibitor (SSRI), as a first-lineantidepressant and, if that is not effective, sertraline or citalopram . There iThe first thing to do when a patient is treatment-resistant is to revisit theformulation and diagnosis. Is this really depression, or does the pattern ofsymptoms since you started seeing the patient suggest a personality disorder asa more appropriate diagnosis? Are there any social factors that have not beenaddressed?Then review whether the patient has indeed had all the treatments to which theyappear to be ‘resistant’. Did they stop fluoxetine after a few days of mild sideeffects and would they be prepared to try again? Did they have a good number ofsessions of evidence-based psychological therapy from a fully trained andsupervised therapist? If they stopped after a few sessions, was this due to aproblem in the therapy or the therapist and would they consider trying adifferent therapist?l-thyroxine  lithium. It is alsoimportant to discuss marketing authorisation regulations for potentialantidepressants in your own country . If you are unsure, it is important to discuss cases with yourconsultant peers and to document this.While the majority of adolescents given an SSRI have mild, transient sideeffects, a small number of patients have rarer and more dangerous side effects,including suicidal thoughts , homicidThere is then the question of whether another SSRI should be used. There is nopublished evidence regarding this. However, in consensus discussions, severalpsychiatrists have tried the patient on a second SSRI and this has not led tothe same side effect. It is likely the patient will have increased risk of, forexample, suicidality on a second SSRI compared to a patient who has never had anSSRI, but it could be worth trying, especially in more severe depression whichitself carries significant suicide risk. As always, it is important to discusspotential benefits and risks with patients and families and make decisionsjointly. It is essential to document these discussions. It is also especiallyimportant to follow these patients up regularly when starting a second SSRI andhave a clear plan in place for what is to be done if these side effects recur.If unsure, discuss the case with consultant peers and document this.It is also important to take into account the pharmacological profile of thefirst and second SSRI. Among the SSRIs, sertraline and citalopram/escitalopramhave significantly higher 5-HT specificity than fluoxetine. So, if sertralinecaused dangerous side effects, it would be better to try the more differentfluoxetine than citalopram as second line.SSRIs are by far the most effective medication for anxiety disorders in children,adolescents and adults . GeneralIf we see a patient with an anxiety disorder who is taking propranolol, we shouldsensitively explain that it is not effective, and offer them an SSRI instead ifthey would like medication. If the child/adolescent has recovered from theanxiety by the time we see them, it is still worth stopping the propranolol asthey may no longer need it. It is also important to educate the GP thatpropranolol is neither safe nor effective for anxiety disorders.One possible exception is children/adolescents with autism spectrum disorder(ASD) and anxiety. Some ASD experts report that children with ASD are much moresensitive to internal somatic stimuli, and if they have pronounced physicalsymptoms of anxiety, reducing these with propranolol may make a big differenceand reduce overall anxiety. However, there is no clear evidence for this, and itis probably more appropriate to try an SSRI first.Repetitive behaviours are a core diagnostic component of ASD and, consequently,commonly observed among individuals with autism of all ages. These behaviourscan take different forms: broadly speaking, while for some they comprise‘functional’ behaviours, such as the pursuit of interests, for others they maybe less purposeful, such as ritualistic and repetitive motor behaviours. Thedecision to treat is fundamentally determined by the degree to which thebehaviour impacts on wellbeing and/or the ability to develop other skills.Treatment of repetitive behaviours will largely be from apsychological/behavioural perspective. In some circumstances, however, these maybe ineffective, or otherwise difficult to implement; in such cases, medicationmay be considered. The Cochrane Review of 2013, which considered the use ofSSRIs in the management of ‘core’ symptoms of ASD, found no evidence to supporttheir use for ritualistic behaviours . A more This notwithstanding, when examining individual studies, there is certainly someevidence to suggest that certain SSRIs , guanfachttps://www.england.nhs.uk/wp-content/uploads/2019/02/STOMP-STAMP-principles.pdf),medication should be discontinued if it does not help, and, among responders,should be monitored and discontinued when appropriate.At the outset it is essential that any trial of medication has (i) a cleartitration schedule and (ii) well-defined outcome measures. It is important tobear in mind that medication may take several months to alleviate symptoms. Inaccordance with the Stopping The Over-Medication of children and young People and Supporting Treatment andAppropriate Medication in Paediatrics (STAMP) frameworks  or aripiprazole – a D2 and 5-HT1A receptor partial agonist (5–10 mg)can be used for this purpose, both having shown efficacy and safety amongautistic individuals at lowerhttps://cks.nice.org.uk/topics/psychosis-schizophrenia/prescribing-information/monitoring/)in relation to risperidone use in children advocates monitoring forhyperprolactinaemia 6 months after starting treatment, and then every 12 months.Collection of blood may not always be possible, in which case the decision tocontinue medication must be made in discussion with the patient and family andclearly documented. Other  antipsychotics may also be used secondline, but less is known about their use in this population. Similarly,benzodiazepines can have both a calming and anxiolytic effect, but there are nodata on their use in this population. There is no evidence that SSRIs areeffective for aggression, and no evidence for the use of mood stabilisingtreatments (unless of course a specific relevant diagnosis of bipolar disorder(BD) has been made). There is also no evidence for using different medicationsin combination.In other situations, the consideration of medication may be raised whenbehavioural therapy has been unsuccessful or only partially successful. It isalways important to consider the reasons for this lack of success, includingrevisiting the possibility of underlying medical causes . As in the acute situation, risperidone oraripiprazole may be introduced, with the expectation that the child is likely toremain on this over a period of 6 months or more. It is important that clinicalmonitoring takes place according to local policy, which in the United Kingdommay vary between NHS Trusts . The FDADeciding on when to discontinue medication is also important, and a decision mustbe taken early in treatment. It may be reasonable to begin discontinuation atthe 6-month point, or sooner for some. However, in reality other factors willinfluence this decision, such as whether or not the child has structure duringthe day (less likely during school holidays) and whether there is additionalsupport available.For some children, behavioural interventions combined with ‘first line’medications such as those suggested above fail to alleviate symptoms. There maybe several reasons for this, and it is crucial at the outset that these areexplored. The diagnostic formulation may have missed an important aetiologicalfactor, or previously identified triggers or perpetuating factors may have beeninadequately managed. For example, an environment with certain characteristics,such as routine, predictability and appropriate level of stimulation, may not bemade available. Or there may be an absence of adequately trained support staffand staff may fail to follow behavioural recommendations. In these circumstancesit is crucial that medication does not become the perceived ‘solution’. It isunethical for the psychiatrist to be expected to medicate where services areunable to meet needs.On the other hand, there will be situations where challenging behaviour continuesdespite attention to all identified aetiological factors. Such situations aremost likely to arise in the context of non-verbal autistic children who areseverely or profoundly cognitively impaired. While it remains important tocontinue to work towards a great understanding of the behaviour’s underpinning,this is often very challenging and medication may thus be considered as a leastrestrictive, best interest option in consultation with decision makers.Additionally, the psychiatrist should discuss treatment-resistant cases withtheir peer group, and consider seeking a second option.Other medications than those already discussed above have much less evidence forefficacy. Other  antipsychotics such as quetiapine – receptorantagonist (D2 and 5-HT2) or olanzapine – D2 and 5-HT2 receptor antagonist – arecertainly reasonable options, although they have not been studied robustly inthis population . ConsequSSRIs do not have a role to play in the management of aggression, and their useshould be limited to the management of mood disorders, anxiety and, in somecircumstances, repetitive and ritualistic behaviours as discussed above.Clozapine-D2, 5-HT2 and NE alpha-2 receptor antagonist are sometimes used tomanage aggressive behaviour in autistic people, but this is based on limitedevidence in adults . There aAs a neurodevelopmental disorder, the features of ADHD are usually present earlyin childhood and often cause functional impairment by the time a child is inprimary school, whereas BD usually presents in teenage years with peak onsetdescribed as between 15 and 19 years . AnotherBD is a disorder of mood characterised by discrete mood episodes. Periods betweenthe mood episodes also described as euthymia are usually characterised by stablepsychosocial functioning. Borderline personality disorder (BPD), also known asemotionally unstable personality disorder (EUPD), is a personality disordercharacterised by a long-term pattern of unstable interpersonal relationships,distorted sense of self and marked affective instability. The affectiveinstability is often triggered by environmental factors and usually lasts hoursto days, unlike the mood episodes in BD which last weeks to months. Otherclinical variables that help distinguish BD from BPD include: response topharmacology in BD, a family history of BD, and the fact that BPD is oftenassociated with significant early life trauma. When in developing individualisedtreatment approach, adopting a dimensional approach in addition to a categoricalapproach, is beneficial particularly when these conditions are co-morbid.Both phenomena can occur quite soon after the initiation of antidepressants. TheInternational Society for Bipolar Disorders Task Force recommends using the term‘treatment-emergent affective switch’ (TEAS) instead of antidepressant-inducedswitch to emphasise association of (hypo-)manic symptoms when treating withantidepressants without implying causality. Different researchers operationalisethe time frame in which TEAS can emerge with In the activation syndrome, symptoms can include impulsivity, insomnia,restlessness, hyperactivity and irritability, while on the other handantidepressant-induced manic switch presents with symptoms of a (hypo-)manicepisode. Mild hypomanic symptoms are much more common than manic switching and it mThere are considerations that relate to the physical complications of eatingdisorders. These include cardiac risks secondary to malnutrition and electrolyteabnormalities secondary to malnutrition or purging. Low weight can causebradycardia and prolong QTc interval, thus increasing the risk of arrythmia, as can Another consideration is patient engagement and adherence with prescribing.Anxiety about, and sensitivity to, side effects need to be addressed directlybefore initiating medication, in particular fear of weight gain secondary toantipsychotics. Patients should be reassured that the small doses ofantipsychotics such as olanzapine typically used will have a minimal impact onappetite, that use of antipsychotics is short term (months rather than years)and that weight can be managed by adherence to meal plans during therapy. Theprimary purpose of prescribing antipsychotic medication in patients withanorexia nervosa is to reduce overwhelming arousal during meal times and notdirectly to cause weight gain.Comorbidities in eating disorders are common – up to 55% of children andadolescents presenting with an eating disorder have a comorbid disorder atpresentation . The comHowever, in some patients, the history clearly suggests that untreated orundiagnosed mental disorder may have preceded onset of the eating disorder andeven that the eating disorder functioned as a ‘solution’ to these feelings ofanxiety or other negative affect. For example, OCD may remerge as anorexianervosa recedes. If a patient is not responding to competently deliveredtreatment as expected, re-evaluation of the diagnosis and formulation andconsideration of additional treatment strategies for comorbidity should beconsidered.Neurodevelopmental disorders are common across mental disorders, and areespecially associated with eating disorders. Studies report between 4 and 52.5%of participants with anorexia nervosa meet suggested clinical cut-off for ASD,with higher proportions in adult that in younger populations . This wiADHD is commonly comorbid in the context of bulimic and binge eating disorder(BED) . IdentifThere are now sufficient high-quality studies to confirm the efficacy ofcannabidiol in treating seizures in both adults and children . The modIn the absence of a history of daytime seizures, the likelihood of undiagnosednocturnal seizures is less. However, there are certain types of epilepsy thatpresent with seizures that occur only or primarily at night.In particular, nocturnal seizures of frontal lobe origin can present in a waythat can be inconsistent with what most people would consider as being typicalof epileptic seizures . NocturnChildren with nocturnal tonic (stiffening) seizures generally have a backgroundhistory of epilepsy. Because they are brief, nocturnal tonic seizures may bedifficult to distinguish from normal nocturnal movements but video EEGmonitoring can be diagnostic. Brief tonic seizures can occur many times in asingle night, sometimes more than 100 times. Such frequent seizures almostcertainly affect daytime alertness and performance.The other nocturnal epilepsy-related phenomenon that is of major importance,although rare, is electrical status epilepticus of slow-wave sleep (ESES),otherwise known as continuous spike-wave of slow-wave sleep . The defwithdepression not taking SSRIs, then those taking SSRIs have a verymuch lower risk of having seizures, as confirmed by the Alper et al. review.Both animal work and the landmark paper by In brief, if someone taking SSRIs for depression has a seizure, the situationshould be discussed fully with the young person/family. It is unlikely that theSSRI will have precipitated the seizure and it is even possible that the SSRImight have some protective benefit against further seizures. The family shouldbe provided with accurate information on which to make a decision. Usually, therecommendation will be to continue with the SSRI, unless there is a clearindication for not doing so. If it is a single seizure with no associatedclinical signs or symptoms that might cause concern, such as, for example, a newabnormality on neurological examination, it is usually not necessary to refer topaediatrician or neurologist. If further seizures occur, full assessment forepilepsy is recommended.Much of the information held in NICE guidance for the initiation of treatment ofOCD are still based on strong evidence . When chIdeally measuring response to treatment with a standardised measure can behelpful to track change. If there is little shift in the core OCD symptoms after3 months at high dosage of an SSRI, cross-titrating to a second SSRI isrecommended. A full 3-month trial, again at high dosing is important. It wouldbe after a second high dose trial that one would consider a trial ofclomipramine or, more commonly, to consider augmentation with low doseantipsychotic medication.Patients who fail to show a good treatment response to SSRI medication mayrespond to the addition of a low dose antipsychotic medication to the SSRItherapy . It is iIn considering this intervention in children and young people, it is importantthat all the typical provisions and considerations be in place for prescribingand monitoring antipsychotics. It is also important to have a sharedunderstanding with the young person and their family about the prospects forimprovement. The data supports the use of low dose antipsychotic augmentation ofan SSRI only. Approximately one-third of treatment-resistant cases of OCD willshow an additional response to adding low dose antipsychotics to the SSRI .It is iWhen treatment for OCD have been suboptimal, children, young people and theirparents often ask for additional switches of medication. This can be animportant moment in clinical practice, to discuss efforts around psychologicaltherapy. Where medications have not brought about the required improvements,young people and their families need to understand that multiple furtherswitches of psychopharmacology are unlikely to be helpful. It can be in thesemoments that one can renegotiate to redouble efforts around CBT for OCD.Personality disorders can and do occur in people under 18 and no diagnosticcriteria say they cannot. Patients can find having an accurate diagnostic labelhelpful; the correct diagnosis helps clinicians to give appropriate treatmentsand the correct diagnosis leads to a more realistic prognosis being given .Making There is no evidence that any medication is effective for the core symptoms ofBPD in adults or adolescents. There is limited evidence that medication iseffective for co-morbid mental illness in adults with BPD and no evidence forthis in adolescents. Instead, the mainstay of treatment of BPD  is complex and integrates psychological therapy programmes. Inparticular dialectical behaviour therapy and mentalisation-based treatment havebeen found to be effective in adolescents with BPD although studies were limitedby including mainly girls and only including the subset of patients with BPD whowere happy to be in a treatment trial . Itis aSchizophrenia has a rise in prevalence during adolescence, which is also the timewhen drug consumption rises. Cannabis, particularly high-potency cannabis, is acommon precipitant or contributor to psychosis in young people . Youth eNICE guidelines advise inquiry about the use of alcohol and illicit drugs whenassessing a young person with psychosis and, if present, about particularsubstances and patterns of use . PerformIf diagnostic criteria for schizophrenia are met in an adolescent with asubstance-use disorder, both diagnoses should be made. Integrated care, in whichtreatment for both disorders is provided simultaneously by the same clinician incommunity-based mental health teams, should be provided . There iTreatment-resistant schizophrenia is defined by persistence of significantsymptoms, despite adequate treatment with at least two different antipsychotics,lasting 6 weeks each, and during which there was no appreciable symptomatic orfunctional improvement, as measured by validated rating instruments .It can Before considering that a patient has a treatment-resistant schizophrenia, weneed to investigate possible causes of lack of effectiveness of prescribedtreatments . After rAccording to NICE guidelines, clozapine should be offered to children and youngpeople with treatment-resistant schizophrenia . This reInitiation of clozapine requires a careful balance of the risk/benefit ratio andcommitment to the increased monitoring requirements by patient, family andpsychiatrist. Psychiatrists should adopt a proactive approach on assessment,intervention and reassurance for patients and families, as most side effectswill appear during the first weeks of treatment and could be managed withoutdiscontinuation .Antipsychotics are associated with weight gain and adverse metabolic effects,particularly in children and adolescents, although mechanisms driving theseeffects are still largely unknown . HoweverIn case weight gain is established, treatment options could include switching toa less orexigenic/metabolically adverse antipsychotic, adjunctive behaviouraltreatments and adjunctive pharmacologic interventions. The IMPACT trial ,enrolleAs both methylphenidate and guanfacine are licensed for the treatment of ADHD,both can be helpful and effective treatments for this condition; however, theco-occurrence of tics is unlikely to be treated adequately usingmethylphenidate. While treating ADHD with methylphenidate can have beneficialeffects on associated symptoms that increase tics , there does not appear to be a direct effect ontics.https://fundingawards.nihr.ac.uk/award/NIHR128472) is examiningthis question in a head-to-head comparison of guanfacine versus methylphenidatefor ADHD.The clinical decision whether to switch to guanfacine or to augmentmethylphenidate with guanfacine is based on: (i) the relative severity of ADHDand tic symptoms, (ii) whether methylphenidate is effectively managing the ADHDsymptoms, and (iii) whether methylphenidate appears to be worsening tics. Ifmethylphenidate is already effective in treating ADHD symptoms, but tics worsenand/or require treatment, guanfacine may be added. In cases of mild to moderateADHD symptoms with co-existing tics, and/or if methylphenidate is only partiallyeffective or poorly tolerated, discontinuation of methylphenidate and switchingto guanfacine may be considered. If tics improve with guanfacine alone but ADHDworsens, then methylphenidate may be restarted. In the cases of mild-to-moderateADHD with co-existing tics (where both require treatment) there is an argumentto suggest that guanfacine monotherapy should be considered as the first-linemedication choice rather than methylphenidate. However, there remains clinicaluncertainty about the best treatment choice in these circumstances, and in theUK the current HTA SATURN trial . Therefore, when a combined Tic and OCS presentation is present andobsessive and/or compulsive symptoms are equally problematic, antipsychoticshave often been used alongside SSRI’s. This effect has also been shown to bepresent with aripiprazole, and the partial agonist profile of this medicationmay point to it being more effective on mood and OCS difficulties. One of thepotential side effects of noradrenergic agents is depression .Typically, antipsychotic medications are also more sedating than noradrenergicalternatives. This might, for example, be beneficial to consider in young peoplewho already using sedating medications such as promethazine.Of note, noradrenergic agents are contraindicated in individuals who experiencesevere bradyarrhythmia secondary to second- or third-degree AV block or sicksinus syndrome. Antipsychotic medications are not contraindicated in this typeof patients, although cardiology opinion would be essential before prescribingantipsychotic medication in this client group. Aripiprazole has the leastcardiac side effect profile of the antipsychotic medications especially relatedto QT prolongation.Recommended clonidine therapeutic doses are in the order of 3–5 mcg/kg/day. It isuncommon to use doses beyond 300 mcg daily, due to the sedating and hypotensiveeffects of clonidine. However, some young people may be able to tolerate thecardiac effects of clonidine well and find that the sedation has additionalbenefits to sleep and comorbidities. Therefore, in these children, higher dosesmay be beneficial with regular monitoring of blood pressure and pulse. Asclonidine can also be divided into two or three doses, quite often children whoare sensitive to guanfacine side effects find that a BD or TDS regime ofclonidine suits them better than the once daily dosing of guanfacine.Clonidine is 10 times more potent than guanfacine at alpha-2 presynapticreceptors, whereas guanfacine appears to be more potent at post synapticreceptors, which translates into increased prefrontal activity and impulsecontrol regulation and improvement in behaviour regulation . TherefoGuanfacine weight dosing guidelines indicate 0.05–0.08 mg/kg/day suggesting thata rough equivalency is: Guanfacine 1 mg = Clonidine 100 mcg.If it is clinically acceptable from a tic perspective to reduce and withdrawalclonidine first, before initiating guanfacine, this is likely to be bestpractise, as the side effects will be additive. Reducing clonidine by 25 mgevery 3–5 days is thought to be appropriate to facilitate this reduction.However, it may not be beneficial from a tic/sleep/behaviour perspective toreduce and withdraw clonidine completely before starting guanfacine. In thesecircumstances, cross-tapering is recommended  by reducWe hope that this article will be helpful for prescribers in their daily clinicalpractice. We also hope that in the near future, additional high-quality evidence,applicable at the individual patient, rather than group level, will inform theanswers to these and other important questions, within the framework of a precisionpsychiatry approach .


Bartonella spp. comprises emergent and re-emergent fastidious Gram-negative bacteria with worldwide distribution. Cats are the main reservoir hosts for Bartonella henselae and dogs represent opportunistic hosts for the bacteria. Even though ticks may also play a role in transmission, their competence as vectors for Bartonella spp. has not been totally understood. Considering only a few studies had a focus on screening Bartonella in animals, humans and ectoparasites in Portugal, this study aimed to address the molecular occurrence of Bartonella sp. in 123 stray cats, 25 stray dogs, 30 humans from Lisbon and 236 questing ticks within the country. Using a qPCR targeting the nuoG gene, it was possible to detect Bartonella sp. DNA on 20.32% of cat samples (25/123). From these positive samples, 13 sequences were characterized as B. henselae, 11 as B. clarridgeiae and 1 presented co-infection with both species. The absolute quantification of nuoGBartonella DNA in sampled cats ranged from 2.78 × 10 to 1.03 × 105 copies/µL. The sampled dogs, humans and ticks were negative. These results showed that B. henselae and B. clarridgeiae are circulating in stray cats from Lisbon. Additional and more extended studies should be conducted to determine the impact of such infections on humans, particularly those in constant and direct contact with cats. Bartonella spp. encompasses small, fastidious, and facultative Gram-negative intracellular bacteria with a global distribution -3′ [® (IDT-Integrated DNA Technologies) encompassing the 83 bp B. henselae-nuoG gene fragment. The number of copies was determined by the following formula: Xg/μL DNA/[fragment length in bp × 660]) × 6.022 × 1023 × plasmid copies/μL.A quantitative PCR targeting a fragment of the NADH ubiquinone oxireductase subunit G (BHQ1]-3′  was carrnuoG-based qPCR gene were afterwards used in two cPCR assays. The citrate synthase gene (gltA) was targeted for amplification of a 767 bp fragment, using the primers 443F: 5′-GCTATFTCTGCATTCTATCA-3′ and 1210-R: 5′-GATCYTCAATCATTTCTTTCCA-3′ [ribC), using the primers BARTON-1: 5′-TAACCGATATTGGTTGTGTTGAAG-3′ and BARTON-2: 5′-TAAAGCTAGAAAGTCTGG CAACATAACG-3′ [gltA cPCR assay and cycling conditions consisted of an initial denaturation at 95 °C for 5 min, 35 cycles consisting of denaturation at 94 °C for 30 s, annealing at 55 °C for 30 s and extension at 72 °C for 1 min, followed by a final extension at 72 °C for 5 min. Ultrapure water was used as a negative control. All assays were conducted in a T100™ Thermal Cycler . PCR products were analyzed by horizontal electrophoresis in 1.5% agarose gel stained with Green Safe Premium (NZYTech). Positive amplicons for both cPCR targeting the genes gltA and ribC were purified using the NZYGelpure kit (NZYTech) and Sanger sequenced at StabVida .Positive samples for the TTCCA-3′ . The 25 TAACG-3′ . ReactioE. coli competent cells (NZYTech) according to standard cloning protocols. Briefly, the purified amplified product was ligated into the plasmid pTZ57R/T. Chemically competent E. coli cells (NZYtech) were transformed, plated in LB agar (NZYtech) and incubated at 37 °C, overnight. Positive colonies were subcultured overnight on 3 mL of LB medium  at 37 °C and under 200 rpm of shaking. Finally, plasmid purification was carried out using the NZY Miniprep kit (NZYtech) following the manufacturer’s recommendations, and 10 µL of purified samples together with 3 µL of M3 forward primer were sent to StabVida , for sequencing. Sequences were manually trimmed and submitted to BLAST [B. henselae gltA, B. clarridgeiae gltA, B. henselae ribC and B. clarridgeiae ribC), and a ClustalW multiple alignment was performed in Bioedit for each group of gene sequences. The number of haplotypes (h) and the haplotype diversity (Hd) was evaluated using the software DNA Sequence Polymorphism (DnaSP) v.6.12.03 [p-distance model with 1000 bootstrap replications. For the phylogenetic trees’ construction, ClustalW multiple alignment was performed in Bioedit for each group of gene sequences (gltA and ribC), including representative sequences for each haplotype obtained in this study, together with other sequences selected from the GenBank (for gltA: Bartonella acomydis (AB444979.1), Bartonella alsatica (AF204273.1), Bartonella birtlesii (AF204272.1), Bartonella vinsonii subp. vinsonii (Z70015.1), Bartonella vinsonii subsp. arupensis (AF214557.1), Bartonella jaculi (AB444975.1), Bartonella rattaustraliani (EU111796.1), Bartonella japonica (AB242289.1), Bartonella coopersplainsensis (EU111803.1), Bartonella quintana (HQ014627.1), Bartonella koehlerae (AF176091.1), Bartonella henselae Human Australia (AJ439406.1), Bartonella henselae (L38987.1), Bartonella henselae Cat Flea Austria (MF374384.1), Bartonella henselae Cat Brazil (MH019304.1), Bartonella henselae Dog Chile (MG252490.1), Bartonella doshiae (AF207827.1), Bartonella rattimassiliensis (AY515124.1), Bartonella queenslandensis (EU111798.1), Bartonella elizabethae (Z70009.1), Bartonella schoenbuchii (AJ278184.1), Bartonella chomelii (AY254308.1), Bartonella capreoli (AF293392.1), Bartonella rochalimae (FN645459.1), Bartonella clarridgeiae Cat flea Chile (KY913636.1), Bartonella clarridgeiae Cat Brazil (MH019302.1), Bartonella clarridgeiae Cat Thailand (KX001761.1), Bartonella clarridgeiae (EU770616.1), Bartonella clarridgeiae strain 73 (FN645454.1), Bartonella baciliformis (DQ452947.1), Bartonella tamiae (DQ395177.1) and Brucella abortus (AE017223.1); and for ribC: Bartonella henselae Cat Brazil (HQ012583.1), Bartonella henselae fleas USA (AY953284.1), Bartonella henselae Cat Brazil (HM588661.1), Bartonella koehlerae (FJ832090.1), Bartonella quintana (AJ236917.1), Bartonella washoensis subsp. cynomysii (DQ825697.1), Bartonella heixiaziensis (KJ361664.1), Bartonella vinsonii subsp. arupensis (AY116631.1), Bartonella vinsonii subsp. vinsonii (AY116636.1), Bartonella vinsonii subsp. berkhoffii (AY116629.1), Bartonella alsatica (AY116630.1), Bartonella fuyuanensis (KJ361648.1), Bartonella doshiae (AY116627.1), Bartonella sp. Bat Kenya (HM363783.1), Bartonella bovis riboflavin synthase France (AY116637.1), Bartonella chomelii (AB290195.1), Bartonella capreoli (AB290194.1), Bartonella schoenbuchensis (AY116628.1), Bartonella bacilliformis (AJ236918.1), Bartonella clarridgeiae Cat China (EU571943.1), Bartonella clarridgeiae (AJ236916.1), Bartonella clarridgeiae Japan (AB292604.1), Bartonella clarridgeiae Cat Brazil (KR092386.1), Bartonella ancashensis (KP720649.1), Candidatus Bartonella ancashi Peru (KC886734.1), Brucella melitensis (CP008750.1)). No criteria regarding host or geographical localization were used to retrieve sequences from GenBank. Likelihood-mapping analyses were performed using the TREE-PUZZLE v5.3 program [Sequences were analyzed and manually cured using Bioedit Sequence Alignment Editor , in ordeto BLAST . Edited .6.12.03 . The hap.6.12.03  was usedlerae AF1091.1, BaBartonella spp. was not detected in ticks, dogs, and humans in the present study, but more studies need to be performed addressing this topic and putting emphasis on Bartonella spp. reservoirs and vectors. Regarding the dogs, surveys among endocarditis afflicted individuals can be carried out and similarly, studies conducted on humans should prioritize immune-compromised groups, as they are more prone to develop infections by Bartonella spp. About 20% of the cats sampled in Lisbon were positive for at least one Bartonella spp. and both B. henselae and B. clarridgeiae were identified in similar percentages. It is hoped that these results could bring attention to Bartonella sp. as an emerging pathogen in cats from Lisbon, and a potential threat for public health. As they are the main reservoir for B. henselae, preventive measurements should be implemented in order to avoid an outbreak of cat scratch disease in Lisbon.Bartonellosis is recognized as an emerging vector-borne disease that constitutes a threat to both animal and human health. Continuous and active surveillance to understand the epidemiological characteristics of bartonellosis is needed worldwide, including in Portugal.


Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric diagnoses among children and adolescents. Depression and general anxiety disorder (GAD) are often co-occurring with ADHD among children and adolescents. Previous studies have found that ADHD, depression and GAD are all strongly correlated with suicidal thoughts and planning.The current study aimed to further explore the association between ADHD, GAD and depressive symptoms as well as their association with suicidal thoughts and planning among adolescents.Adolescents with ADHD diagnosis were involved from child psychiatry outpatient clinics and adolescents without a psychiatric treatment or diagnosis were enrolled from high schools in Hungary. The Mini International Neuropsychiatric Interview for Children and Adolescents was used to evaluate psychiatric symptoms and disorders as well as suicidal thoughts and planning. Regularized psychological networks were used to investigate the associations.Altogether 185 adolescents , 89 with ADHD and 96 without ADHD were enrolled. Depression symptom worthlessness was directly related to suicidal thoughts and planning, CI95 of the logit B between worthlessness and suicidal thought . Both ADHD and anxiety were indirectly related to suicidal thoughts and planning through depression: CI95 of the logit B between being disorganized and feeling worthless is , and CI95 of the logit B between being distressed and feeling worthless is .This study draws the attention of clinicians to the importance of recognizing “worthlessness” for suicide prevention in adolescents with ADHD. Furthermore, the results support previous studies, whereby symptoms of depression and anxiety mediate the relationship between ADHD and suicidal thoughts and planning. These results highlight the importance of ADHD comorbidities with depression and GAD and their effect on suicidal thoughts and planning. Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently diagnosed mental disorders among children and adolescents, with a prevalence of 4–6% , 2. It iRecently, several researchers have focused on adolescents with ADHD and internalizing comorbid psychiatric problems , 9 and dBased on previous research, suicidal thoughts and planning are strongly associated with ADHD , 15–19. Brown et al.  found whIn sum, our previous study, among others, revealed a triple-pathway model between attentive-disruptive disorders and suicidality: the association between the two variables were mediated by affective, psychotic, and anxiety disorders , 9, 21. Based on the previous literature, we established the following hypotheses:Both symptoms of anxiety and depression mediate the relationship between ADHD and suicidal thoughts and planning in adolescence.There is a direct association between the symptoms of ADHD, anxiety and depression with suicidal thoughts and planning.Furthermore, we aimed to identify which symptoms of depression and anxiety are the major contributors to suicidal thoughts and planning in adolescents with ADHD.The entire protocol of the study and the characteristics of the sample have been previously published .The Ethical Committee of the Medical Research Council, Hungary  approved the study. Participants and their parents/caregivers were informed about the study in written and oral forms. All participants and their parents/caregivers gave their oral consent, and participants older than 14 years and all parents/caregivers provided written informed consent.An ADHD and a control group were enrolled. The inclusion criterion for both study groups was to be between the ages 13 and 18 years. A further inclusion criterion for the ADHD group was previous ADHD diagnoses by a clinician and a structured interview (see below). The control group's inclusion criteria were the absence of present or previous psychiatric diagnoses and treatment. The exclusion criterion for both groups was intellectual disability in the medical history. The participants for the ADHD group were from four different child psychiatric outpatient clinics in Hungary, while the control group consisted of three different high schools in Hungary. From the high schools around Baja, Hungary, 132 adolescent and their parents were contacted to participate in the research and at the end 96 adolescents and their parents completed the questionnaires (response rate: 72.73%).Demographic questions were asked of the participants' parents. These questions were developed explicitly for the current research. These included information about the parental education level, the economic activity of the parents, previous psychiatric diagnoses/treatment of family members, and the structure of the family.The modified version of the Mini International Neuropsychiatric Interview for Children and Adolescents (M.I.N.I. Kid) has been used to assess twenty-four psychiatric diagnoses, including ADHD, major depressive episode and GAD , 29. TheStatistical analysis was performed using R . As we had no prior assumptions about the exact paths through which different ADHD, anxiety and depression sub facets as well as suicidal ideation are interconnected, we did not use any models  that predefine independent, mediator and dependent variables. Instead, we opted for regularized psychological networks that are widely used in psychiatry and clinical psychology –38.Models in network psychometrics presume that observed variables have a causal influence on each other. In this perspective, correlations (edges) between variables (nodes) originates from mutual relationship between the symptoms rather than from the presence of latent variables . In thisThe alphanumeric nodes labels in the figures through the article represent questions regarding the symptoms of ADHD, anxiety, depression and suicide behavior as they are listed in the M.I.N.I Kid. In the case of binary variables, Ising models  that areNevertheless, network edges are never zero due to sampling variation, but they can mirror spurious correlations or, in other words, false positives . As multAs a first step, we aimed to map the facets of each mental disorder. To do so, the first author manually categorized the items. Subsequently, unregularized Ising networks were estimated for each disorder that depicts the intercorrelation of the items. Instead of the DSM-5 based two ADHD symptom domains , in the current analyses the ADHD part of the M.I.N.I. Kid was categorized into four specific symptom domains to best understand the relationship of the variables. Based on previous research, intrusive –51, and As a second step, these binary factor variables were used in one large regularized network to map the conditional relationship between the different facets of ADHD, anxiety, depression and suicidal thought and planning. To obtain confidence intervals for the regression coefficients, bootstrapping was used with 1,000 bootstrap samples. Bootstrap results measure how often a given edge was estimated to be non-zero. Due to the regularization, all estimates are biased toward zero; hence, the entire sampling distribution is biased toward zero. It implies that the bootstrapped confidence intervals are not centered on the unbiased parameter value. Therefore, just as previously, if the bootstrapped interval contains zero, it could be that the unbiased one does not. However, if the bootstrapped CI does not overlap with zero, then the unbiased one does not overlap either .After bootstrapping the results, the stability of our network was assessed. To do so, we estimated six network models with different hyperparameters and compared them along three commonly used centrality measures. In a model estimated with an EBIC LASSO, the gamma hyperparameter determines the sparsity of the network: higher values lead to the removal of more weak  edges, while lower values may retain more  correlations. We compared networks along strength, betweenness and closeness. Node strength reflects the sum of absolute edge weight associated with a certain node, betweenness counts how many times a given node is in the shortest path between two other nodes, and closeness calculates the inverse of the sum of distances from a node to all other nodes measuring how close a given node is to all other nodes . All of 2(1) = 37.87, p < 0.0001, Wilcoxon for age differences was: W = 3,885, p = 0.28. The proportion of participants with any suicidal thought was 92.97%.In the present study, the total number of participants with ADHD were 89, and the number of participants in the controls were 96. Regarding gender, 58 females and 127 males participated in the study. The mean age was 14.79, SD = 1.48 and for gender: χp < 0.0001, V = 0.46].We found a significant difference between gender between the two groups, in the ADHD group 92% were males and in the control group 54% were males [Xp < 0.001) and of suicidal thoughts and planning , but not with anxiety . Suicidal thoughts and planning were significantly related to depression , but not to anxiety . Anxiety was significantly associated with only depression .First, four variables were created by summing the items and Spearman correlations were calculated see . The numSecond, unregularized Ising networks were estimated for all four disorders separately to map the factor structure. The network models are shown in After the categorization, items were collapsed based on the facets; distributions are shown in Third, after creating the binary categories, the regulated Ising network model was estimated with one suicidality (thought and planning), three anxiety , four depression , and four ADHD  variables .Although the zero-order correlations with suicidality were significant both for ADHD and depression, based on the network model, only depression was directly related to suicidal thoughts and planning, CI95 of the logit B between worthlessness and suicidal thought . Both ADHD and anxiety were indirectly related to suicidal thought through depression: CI95 of the logit B between being disorganized and feeling worthless is  and CI95 of the logit B between being distressed and feeling worthless is . Hence, although hypothesis 1 is fully supported, hypothesis 2 is only partially supported.To our knowledge, our current study is the first one which investigated the relationship of anxiety, depression, ADHD and suicidal ideation using a causal system perspective, where we identified the symptoms of the disorders and analyzed them using a network approach, following the analysis of Fried and Nesse . FurtherIn line with several previous findings, our first hypothesis was supported , 18, 24,In the current study, we identified worthlessness and disorganized path of depression as the primary contributor to suicidal thoughts and planning. Worthlessness was first recognized in the Diagnostic and Statistical Manual of Mental Disorders 3rd Edition as one of the leading symptoms of depressive disorder . The freOur second hypothesis was only partially supported because we did not find a direct association between ADHD, anxiety and depressive symptoms with suicidal thoughts and planning. However, our results indicated that anxiety is associated with suicidal thoughts and planning but only through the worthlessness symptom of depression. There are few studies which focus on depressive symptoms as the mediator between anxiety and suicidal thoughts and planning among adolescents. Hill et al.  had simiThe current study should be considered with the limitation of being cross-sectional, that is why we are not able to draw a causational relationship between the variables. Another limitation is that we found a low endorsement of suicidal thought and planning in our sample. Also, in the study male subjects dominated in the ADHD group. Finally, a potential selection bias could be present by looking at individuals with ADHD diagnosis in treatment.In conclusion, we would like to highlight that our research supported previous findings since we also found that adolescents with ADHD had an association with suicidal thoughts and planning through depression and anxiety , 18. In 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 the Ethical Committee of the Medical Research Council, Hungary . Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.Conceptualization and basic aspects of the methodology used was accomplished by JB. The formal statistical analysis and visualization was performed by DK. Investigation, data curation, and project administration was made by LK-P. Resources were provided by JB. LK-P made the original draft preparation, while the review and editing was made by all authors. Supervision and funding acquisition was organized by JB. All authors provided final approval of the version of the manuscript for publication and agreed to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Children with Autism Spectrum Disorder (ASD) and Attention‐Deficit/Hyperactivity Disorder (ADHD) have an increased obesity risk. Although these conditions commonly co‐occur, shared factors relating to obesity risk are unknown.To examine the shared and unique associations of ADHD and autistic traits with eating behaviours and BMI.N = 4134) from the population‐based Generation R Study were categorized into subgroups based on parent‐reported ADHD and autistic traits scores at 6 years: ADHDHigh, ASDHigh, ADHD+ASDHigh and REF (reference group: ADHD+ASDLow). Multiple linear regressions examined the associations between subgroups and eating behaviours (at 10 years) and BMIz (at 14 years), relative to REF. Mediation analyses tested the indirect effect of subgroup and BMIz through eating behaviours.Children  and avoidant eating behaviours . ASDHigh children were more food avoidant, while ADHDHigh children had more food approach behaviours and greater BMIz. ADHDHigh and BMIz were indirectly associated with food responsiveness and emotional overeating.ADHD + ASDADHD and autistic trait phenotypes show distinct associations with potential obesity risk factors, and further research is needed to improve targeted early intervention. A second aim was to examine the association of ADHD and autistic traits at 6 years with BMIz score at 14 years, and explore whether this is mediated by eating behaviours at 10 years.22.1n = 7254) was obtained from children and their parents. Children with full information on ADHD and autistic traits at 6 years and appetitive traits at 10 years were included in the analyses for aim 1 (n = 4314). Compared to children included in the analyses, those excluded due to missing values (n = 2940), more often had a non‐Western background, a lower birthweight, and a higher BMIz at 14 years; their mothers were younger, had lower levels of education, and higher psychopathology symptom scores . The second aim consisted of a subsample of n = 3495 children who had additional information available on BMIz at 14 years , a population‐based cohort on health and development from fetal life onwards. All pregnant women living in Rotterdam, the Netherlands, with an expected delivery date between April 2002 and January 2006 were invited to participate (participation rate: 61%). The study was conducted in accordance with the guidelines proposed in the World Medical Association Declaration of Helsinki and has been approved by the Medical Ethical Committee of Erasmus Medical Center Rotterdam. Written informed consent was obtained from parents of all children. Full consent for participation in phase 3 of Generation R  to ‘2’ (Often) in the past month. Items were summed to produce an overall sum score for each subscale. The internal reliability for each subscale was acceptable .Parents (93% mothers) completed the well‐validated Child Behaviour Checklist (CBCL)/1.5–5t > 65) on the CPRS‐R:S ‘Hyperactivity’ scale, 73% also had ‘high’ ADHD traits (≥80th percentile) on the CBCL.n = 51 of children in our sample met the clinical cutoff.n = 47). Therefore, using the binary scores derived from the 80th percentile CBCL cut‐points, children were then categorized into four subgroups based on these binary variables: high ADHD traits , high autistic traits , high ADHD and autistic traits  and a reference group of children with low ADHD and autistic traits .The optimal approach to examining the shared and unique characteristics of ASD and ADHD in population‐based cohorts is highly debated.2.2.2α = 0.84–0.92). Z‐scores for each subscale were created to facilitate effect size comparisons.At child age 10 years, parents completed six subscales from the widely‐used Children's Eating Behaviour Questionnaire (CEBQ).2.2.32)] and sex‐ and age‐adjusted BMIz score was obtained based on Dutch reference growth curvesChildren's height and weight were measured by research assistants at the researcher center visit at age 14 years. Height and weight were measured without shoes and heavy clothing. Height was measured to the nearest millimetre by a stadiometer . Weight was measured to the nearest gram using an electronic scale . BMI was calculated [weight (kg)/height . Two‐sided statistical significance was set as 2.3.1High, ASDHigh, ADHD + ASDHigh and REF) were entered as the independent variables and separate models were run for each eating behaviour as the outcome variables. Each model controlled for covariates. Multiple imputation on missing covariates was performed in the MICEMultiple linear regression models were run to examine the unique and combined effects of elevated ADHD and autistic traits on eating behaviour within the sample. Dummy coded variables for the ADHD and autistic traits subgroups .Sociodemographic characteristics of the full sample and stratified by subgroup are shown in Table 3.1High group showed increased scores across all eating behaviours compared to the REF group, except for enjoyment of food where they had a relatively lower score. Children in the ADHDHigh group showed greater food responsiveness, emotional overeating, emotional undereating and picky eating scores relative to the REF group. Children in the ASDHigh group showed greater food responsiveness, emotional undereating and picky eating scores relative to the REF group. In addition, the ASDHigh group had lower food responsiveness scores compared to the ADHDHigh and ADHD + ASDHigh groups; and lower emotional overeating compared to the ADHD + ASDHigh group. The ADHDHigh group had significantly lower estimates for picky eating compared to the ASDHigh and ADHD + ASDHigh groups. Only one sex interaction was observed for the ASDHigh subgroup on enjoyment of food (p = 0.046). Boys in the ASDHigh subgroup had a lower enjoyment of food compared to the REF subgroup  and this association was not significant in girls (p = 0.95). The independent effects of ADHD and autistic traits as continuous variables on eating behaviours are shown in Table Multiple linear regression models for the effect of ADHD and autistic traits subgroup on eating behaviours are shown in Table 3.2n for each group: ADHDHigh = 517, ASDHigh = 360, ADHD+ASDHigh = 318 and REF = 2300). A slightly higher proportion of BMIz data at 14 years were available for children in the REF and ADHDHigh groups (82% for each group) compared to the ASDHigh (79%) and ADHD + ASDHigh (76%) groups . Children in the ADHDHigh group had a greater BMIz at 14 years relative to the REF group  and outcome variables (BMIz at 14 years).Children with complete BMIz data at 14 years were included in the second analysis (ss Table . Only foHigh (vs. REF) subgroup on BMIz through food responsiveness was statistically significant . The direct effect of ADHDHigh (vs. REF) on BMIz was no longer significant once accounting for the indirect effect of food responsiveness , suggesting full mediation through food responsiveness. In the emotional overeating mediation model  subgroup on BMIz through emotional overeating . The direct effect of ADHDHigh (vs. REF) on BMIz remained significant when accounting for the indirect effect of emotional overeating , suggesting partial mediation through emotional overeating.In the food responsiveness mediation model Figure , the indl Figure , there wRerunning the analyses without imputing missing values on covariates produced similar results.4High) at 6 years expressed more ‘extreme’ eating behaviours at 10 years than the referent children (REF), showing both more food approach  and more avoidant behaviours . Regarding unique effects, children with high autistic traits only (ASDHigh) generally expressed food avoidant behaviours more frequently, while children with high ADHD traits only (ADHDHigh) generally expressed food approach behaviours more frequently. Children with high ADHD traits (ADHDHigh) had a greater BMIz score at 14 years relative to the referent children, and this association was mediated by two food approach behaviours: food responsiveness and emotional overeating. Regardless of associations with weight, extreme levels of food approach and/or avoidant eating behaviours may require parents to redirect children's focus on eating, coax them to eat or manage disruptive behaviour during mealtimes, thus impacting the family's mealtime experience.This study examined how ADHD and autistic traits in the general paediatric population relate uniquely and combined to various eating behaviours and weight. Results show that children with elevated ADHD and autistic traits scores (ADHD + ASDHigh) had a unique eating profile suggesting both avid and restricted appetites. This is difficult to interpret, because many of the food approach dimensions tend to inversely correlate with food avoidant dimensions on the CEBQ.High and ADHDHigh subgroups. High negative affect and emotion dysregulation are common in ADHD and ASD,Studies have rarely investigated the co‐occurrence of elevated ADHD and autistic traits, and their potential shared obesity risk factors. In our population‐based cohort, children with the high‐level ADHD and autistic trait phenotype (ADHD + ASDHigh). The scant literature available examining relationships between ADHD traits, eating behaviours and BMI suggests that ADHD traits may precede changes in eating and BMI.n = 100) showed that ADHD traits such as inattention and/or hyperactivity predicted increases in food responsiveness, emotional overeating and BMIz score at 7 years, while the reverse association was not significant.High (vs. REF) on BMI was explained indirectly through food responsiveness, while 9% was explained indirectly through emotional eating. This is perhaps unsurprising, as food responsiveness is associated with a greater preference forFindings from the current study replicate well‐documented clinical associations between ADHD and increased risk of overweightHigh) tended to show more food avoidance, with greater picky eating, emotional undereating and lower enjoyment of food (in boys only) compared to children in the referent group. In addition, we found that children in the ASDHigh subgroup were reported to be pickier eaters but less food responsive than the ADHDHigh subgroup. Taken together, these tendencies may be attributed to eating phenotypes previously reported in children diagnosed with ASD, such as restricted food preferences and dietary intake , and also a tendency to overeat palatable, well‐liked foods .Children with high‐level ASD traits  could be used to investigate the association between ADHD and autistic traits, and variability of eating behaviours at a state‐based level . Future research could also explore different developmental stages, as associations with BMI may not emerge until a later age, particularly as adolescents become more autonomous in eating.ADHD and ASD have overlapping featuresADHDAttention‐Deficit/Hyperactivity DisorderHighADHD+ASDsubgroup with ≥80th percentile scores on ADHD and autistic traitsHighADHDsubgroup with ≥80th percentile score on ADHD traits and <80th percentile score on autistic traitsASDAutism Spectrum DisorderHighASDsubgroup with <80th percentile score on ADHD traits and ≥ 80th percentile score on autistic traitsBMIBody Mass IndexCBCLChild Behaviour ChecklistCEBQChildren's Eating Behaviour QuestionnaireCPRS‐R:SParent Rating Scale–Revised Short FormDSMDiagnostic and Statistical Manual of Mental DisordersREF<80th percentile score on both ADHD and autistic traitsHolly A. Harris, April Bowling and Pauline W. Jansen conceived the research; Holly A. Harris performed the statistical analyses; Holly A. Harris, April Bowling and Pauline W. Jansen interpreted the results and wrote the paper; Susana Santos and Kirstin Greaves‐Lord critically reviewed the manuscript for important intellectual content; Holly A. Harris has primary responsibility for the final content. All authors have read and approved the final manuscript.No conflict of interest was declare.Data S1 Supporting inforamtion.Click here for additional data file.