Attention-deficit hyperactivity disorder (ADHD), characterized by periods of inattention, overactivity, and impulsiveness, is the most prevalent neurodevelopmental disorder among children. Auditory Brainstem Response (ABR) is a technique in which clickshaped sounds elicit potentials that are recorded from electrodes placed on a patient’s skull. Extant research indicates that ABR is frequently affected in neurodevelopmental disorders such as ADHD. Methylphenidate (MPH), a psychostimulant, is often prescribed to children with ADHD as a first-line pharmacological treatment. The aim of this study was to explore the effects of Methylphenidate treatment on previously observed amplitude alterations in the ABR of patients with ADHD.We recruited 32 drug-naïve children and adolescents  diagnosed with ADHD and 35 health controls . The ADHD group was treated with Methylphenidate, and ABR was recorded before treatment and at a steady state of medical treatment.Medicated ADHD patients exhibited increased activity in the right side ABR in Wave VI.A significant increase in activity was found in a part of the ABR thought to correspond to the thalamic area in medicated ADHD patients compared to the same area of non-medicated ADHD patients. The results add to the growing body of research suggesting that specific ABR peaks correlate to certain psychiatric symptoms. ABR traditionally uses click sounds at predetermined intervals and calibrated electrodes placed on the skull to measure the processing that occurs in the basic auditory pathways situated in the brainstem in order to avoid recording later responses from cerebral clusters of higher processing complexity. Using complex stimuli, as in forward and backward masking, the sounds in ABR are similar to sounds in everyday hearing. Complex stimuli may reveal aberrations that would be missed by standard audiological ABR procedures.912 The ABR consists of seven positive peaks (Wave I–VII) recorded by surface electrodes on the mastoid processes of each ear and the forehead. Previous research indicates that Waves III are generated in the auditory nerve, Wave III in the cochlear nucleus, Waves IV and V in the mid-brain, and Waves VI and VII in the thalamus, specifically the medial geniculate body (MGB)  recordings of neural activity in response to a specific, repeated stimulus, are known as Event Related Potentials (ERP). The ERP is known as Auditory Brainstem Response (ABR) when sound is the stimulus of choice. ABR has been used by pediatricians to diagnose possible hearing defects since the 1970s.y (MGB) .14 bipolar disorders, autism spectrum disorders,1517 and ADHD.19Based on research indicating that specific ABR peaks are correlated with certain psychiatric symptoms, it has been speculated that ABR could be used as a complementary clinical tool to aid in the diagnosis of schizophrenia,21 ADHD symptoms are believed to partly emerge from catecholamine neurotransmission dysfunction predominantly in the prefrontal cortex. MPH produces its therapeutic effects by elevating the levels of extracellular synaptic dopamine (DA) and norepinephrine (NE) via reuptake transporter inhibition and vesicular monoamine transporter 2 (VMAT-2) redistribution in the central nervous system. MPH also functions as an agonist at the serotonin 1A receptor (5-HT1A), which partially regulates dopamine release.23 MPH-related enhanced DA and NE neurotransmission is hypothesized to engage selfcontrol regulation networks, reducing the severity of ADHD symptoms.25 There is very little research on ABR and ADHD in children but even less on the potential effect of MPH on ABR. To our knowledge Jonkman et al. are the only ones that have studied the possible effect of MPH on ABR. Jonkman et al. showed that MPH normalized ABR amplitudes in children with ADHD suggesting that its effects might be established through influences on the posterior  cortex.Methylphenidate (MPH) is a psychostimulant commonly prescribed as a first-line therapy for pediatric ADHD.Our aim in this exploratory study is to compare the peak ABR amplitudes corresponding to Waves I-VI (P1-P6) before and during MPH treatment in children with ADHD.Mean Age = 11 ± 2.6, 41% female) and 35 HC . The ADHD group was treated with MPH, and ABR was recorded at baseline and after one month during which they had been titrated up to methylphenidate 36 mg. Nine patients chose to withdraw from the study before the second ABR, leaving a total of 23 patients .This study was conducted April to September in 2021 it included 32 drug-naïve patients with ADHD . A senior child and adolescent psychiatrist confirmed all ADHD diagnoses.Patients with concurrent psychiatry diagnoses including intellectual disability and hearing impairments verified through interviews with parents were excluded from the study. All patients were drug naïve.Patients were instructed not to have any intake of activating substances such as energy drinks, Coca-Cola, or coffee prior to the tests.Written informed consent was obtained from all the subjects and their parents/guardians. The study was approved by the regional ethics committee at Lund University (Dnr: 2021-00351).SensoDetect BERA (Brainstem Evoked Response Audiometry) A1000 was used to record ABRs. Stimuli were presented binaurally in phase via TDH-50 P headphones with Model 51 cushions . Click pulses were presented until 1024 accepted evoked potentials were obtained for each stimulus. Recording sweeps were coordinated with the auditory stimuli using transistor-transistor logic (TTL) trigger pulses.Stimuli sound levels were calibrated with a Bruel & Kjaer 2203 sound level meter and type 4152 artificial ear . The acoustic output power of stimuli measured from the headphones corresponded to SPL: 80 dB HL or 109 peSPL . All recorded data for each sound stimulus from each ear of every study participant were imported into Microsoft Excel  for statistical analysis.A square-shaped click pulse was used as a probe for both the standard ABR stimulus and the auditory forward masking condition. The total duration time of each probe was 0.136 ms with a rise and fall time of 0.023 ms and had an interstimulus interval (ISI) of 0.192 s. A 1500 Hz low pass filtered noise (Butterworth filter) with a duration of the 0.015 s including a 0.004 s rise and fall time was used as masker. The masker and target probe were separated with a 0.012 s gap.The stimuli were created using MATLAB Signal Processing Toolbox  and stored in flash memory in the SensoDetect® BERA system. Surface electrodes were attached to the skin over the mastoid bones behind the left and right ear. A ground electrode and a reference electrode were placed on the vertex and forehead, respectively. Before presenting the auditory stimuli, the procedure was fully explained to the test subject. The click stimuli were presented beforehand to acquaint the participant with the sounds. Before and after the experiments, absolute impedances and interelectrode impedance were measured to ascertain that electrode contact was maintained below 5000 Ω. The subjects were instructed to close their eyes and to relax. Test persons were permitted to fall asleep during the test as no active participation was needed. The subjects were tested one at a time with a total duration of 15 min. At the time for the second ABR the patients were all at a dose of 36 mg MPH.Participants were seated in an armchair in a resting position. The tests were performed in a quiet and darkened room with Farraday’s cage put around the patient to avoid electrical interference.U test was used to measure statistical differences.The ABR curve quality check was measured through whole curve correlation  between the specific patient and the norm ABR curve. The norm ABR curve consisted of the median representation from a group of normal hearing healthy controls. This method is a standard operating procedure to grant ABR quality. Collected evoked potentials for each sound stimulus from each individual were imported to Microsoft Excel  and analyzed using SensoDetect® BAS. We studied the peak-totrough amplitudes in six peaks . For each subject, amplitudes for left and right were identified for the square-shaped click as the target stimulus preceded by a masker of 70 dB (FM). The amplitudes were calculated by subtracting the minimum value from the preceding max value in the peak-to-trough area for each peak, as defined by the healthy control group average curves. Four ABR waveforms were obtained from each test subject (two left and two right) and 20 values. The nonparametric Mann–Whitney p = 0.008, z = −2.414.We studied the ABR under forward masked condition looking at the peak-to-trough amplitudes of the characterized peaks in the brainstem audiograms for both ears. We looked at values for five peaks: P1, P2, P3, P5, and P6. P4 was excluded due to missing values. Due to drop out, it was only possible to collect data on 23 of the 32 medicated patients with ADHD. We found that P6 peak-to-troughs were significantly greater on the right side for ADHD subjects compared to the unmedicated ADHD subjects , p = 0.0 To further substantialize our findings, we compared our data to age- and gender-matched healthy controls  who studied ABR latencies, are advocating for more research into cortico-striato-thalamo-cortical (CSTC) loops. Our findings should be looked upon in relation to other neuropsychiatric groups such as autism spectrum disorder. Our findings are well in line with research showing that the thalamus is key in hyperarousal and increased alertness, a pervasive problem for children with ADHD. Positive effects of MPH on ABR amplitudes are thought to be mediated by NE projecting from locus Coeruleus via Thalamus to the cortex.25 This pathway is important for attention processing.34The role of the thalamus is thought to be prominent in cases of ADHD. Previous studiesOur results add to the growing body of research suggesting that specific ABR peaks correlate to certain psychiatric symptoms. The paradigm built on this hypothesis has previously even led to suggestions that ABR could be used as a complementary diagnostic tool in psychiatric settings and our findings contribute to the evidence supporting the potential of ABR as a complementary diagnostic tool in the future.Limitations of this study include that the results are based on group differences. It is well known that there are gender-based differences in ADHD and the overrepresentation of male ADHD subjects might have influenced the result. Furthermore, our study has a restricted age range, leading to limited generalizability to older populations. An additional source of potential bias is a relatively small sample size and a loss to follow-up. Nine of the participants withdrew from the study leading to missing observations that may lead to bias in the effect estimate. The primary reason for loss to follow-up was the gap in time between study visits (≥1 month). Lastly, the present study’s hypotheses and interpretations are based on a reductionistic approach to psychiatry positing that higher order mental disorders  are the result of lower order biological abnormalities .The authors acknowledge that this approach may bias our interpretations.The significance of right-side aberrations in ABRs should be further investigated. As the number of participants where limited, further studies with more patients could clarify the impact of MPH on ABRs in ADHD pediatric patientsFuture research could investigate whether other ADHD medications also have an impact on ABRs. In addition, longitudinal studies are needed to evaluate the causal link between psychostimulant medication use, ADHD, and ABRs.


Children with attention deficit hyperactivity disorder (ADHD) exhibit pervasive difficulties in speech perception. Given that speech processing involves both acoustic and linguistic stages, it remains unclear which stage of speech processing is impaired in children with ADHD. To investigate this issue, we measured neural tracking of speech at syllable and word levels using electroencephalography (EEG), and evaluated the relationship between neural responses and ADHD symptoms in 6–8 years old children. Twenty-three children participated in the current study, and their ADHD symptoms were assessed with SNAP-IV questionnaires. In the experiment, the children listened to hierarchical speech sequences in which syllables and words were, respectively, repeated at 2.5 and 1.25 Hz. Using frequency domain analyses, reliable neural tracking of syllables and words was observed in both the low-frequency band (<4 Hz) and the high-gamma band (70–160 Hz). However, the neural tracking of words in the high-gamma band showed an anti-correlation with the ADHD symptom scores of the children. These results indicate that ADHD prominently impairs cortical encoding of linguistic information  in speech perception. Attention deficit hyperactivity disorder (ADHD) is a common childhood mental disorder characterized by attention deficit, hyperactivity and/or impulsivity, and cognitive dysfunction . ExtensiOn the one hand, it has been hypothesized that children with ADHD have difficulties in neural encoding of acoustic features, especially for a complex auditory scene consisting of multiple acoustic distractors. Evidence shows that children with ADHD  have reduced neural responses to target sounds under distractors . It is aOn the other hand, speech perception entails not only acoustic encoding, but also higher-level linguistic processing. Since children with ADHD usually suffer from co-occurring linguistic impairments , it has Despite converging evidence for neurocognitive deficits in speech perception for children with ADHD, few studies have analyzed the underlying neural mechanisms across multiple processing stages. One methodological challenge is the difficulty in dissociating neural representations of multiple stages in speech processing. Here, we adopted a hierarchical auditory linguistic sequence paradigm to quantify the neural responses tracking two levels of speech units, i.e., syllables and words . The ratThe study was approved by the Ethics Committee of Children’s Hospital of Zhejiang University . For this study, 23 drug-naïve children  were recruited from Children’s Hospital of Zhejiang University. All children were referred for participation in the study by teachers or parents, and had a diagnosis of ADHD by a pediatrician. All children were right-handed, with no self-reported hearing loss or neurological disorders. Written informed consent was obtained before the experiment. Parents of these children completed the Chinese version of SNAP-IV ADHD Questionnaire . The SNA1 All syllables were adjusted to the same intensity and duration  following the procedure in The speech was created as an isochronous sequence of independent Chinese syllables, and every two syllables constituted a noun word . Fifty cFor each participant, the 35 trials were presented in a random order. The participants were asked to detect whether the probe word “grandma” was presented in the speech by pressing a key (“1” for “yes” and “0” for “no”). The next trial was presented after an interval randomized between 1 and 2 s (uniform distribution) after the key press. After the experiment was finished, the SNAP-IV ADHD Questionnaire was collected from the parents of the children, and the ADHD symptom scores are shown in All preprocessing and analysis in this study were performed using MATLAB . EEG data was acquired on a 32-channel Hydrocele Geodesic Sensor Net (GSN) by Magstim EGI  with 500 Hz sampling rate. The EEG recordings were referenced to the average of 32-channel recordings. Occasional large artifacts in EEG/EOG, that is, samples with magnitude >1 mV, were removed from the analysis . For theAfter data preprocessing, an 8-s epoch of EEG signal was obtained for each trial, and therefore the frequency resolution of the DFT analysis was 1/8 Hz. The EEG signal in the analysis window was transformed into the frequency domain using the discrete Fourier transform (DFT) without any additional smoothing window. Then, the inter-trial coherence (ITC) was calculated following :i was the phase at the frequency bin i in trial n. The ITC is a scalar measure bounded between 0 and 1.where ∅Most previous studies use invasive brain imaging  to investigate neural tracking of speech in high-gamma activity . NeverthHilbert function in MATLAB. Then, each amplitude was normalized to its mean value in each band, and all amplitudes were averaged to obtain the high-gamma amplitude. In the frequency domain analysis, the high-gamma amplitudes were down-sampled to 60 Hz, and divided into 8-s trials. The ITC was calculated for the high-gamma amplitude following the same procedure as adopted in the analysis of the low-frequency signals.High-gamma amplitude were extracted following the procedure in p-value was further adjusted using the false discovery rate (FDR) correction  in the FieldTrip Matlab toolbox  (d and power were reported in A ion 3.1) . The effp = 0.45, HYP/IMP scores: p = 0.14, ODD scores: p = 0.18, Pearson’s correlation, FDR corrected, The experiment presented isochronous syllable sequences , and thep = 0.0001, bootstrap, FDR corrected), and at the word rate . The topography of ITC showed a central distribution. All these findings suggested that low-frequency cortical activity exhibited neural tracking of syllables and words during active speech comprehension in children with ADHD, similar to healthy adults , and at the word rate  for high-gamma amplitude. Moreover, the topography of high-gamma ITC showed a central-frontal distribution at the word rate and a central-posterior distribution at the syllable rate, which is similar to recent studies on high-gamma activity  nor in the high-gamma band . At the word rate . In the high-gamma band, however, the word-rate ITC values was anti-correlated to the INATT scores  and the HYP/IMP scores  while the correlation between word-rate ITC and ODD scores was not significant . A data-driven analysis of individual electrodes further showed the topography of correlation in high-gamma band was located at central-frontal electrodes , consistent with the distribution of word-rate response in the high-gamma band  during speech perception.It is commonly observed that cortical activity tracks speech at different levels, corresponding to low-level acoustic features and high-level linguistic information . Using tAlthough cortical activity consistently tracks the temporal dynamics of speech in both low-frequency and high-gamma bands, they have non-redundant tracking properties and functional roles in speech perception . For exaPrevious studies on healthy individuals have demonstrated that high-gamma neural activity is associated with processes of attention , workingThere are also limitations in the current study. It should be noted that the children who participated in the current study only had mild ADHD symptoms since we found children with severe ADHD were hard to remain stationary and complete all experimental procedures during EEG recordings. Although the current studies exhibited that ADHD symptoms were only correlated with neural impairment in linguistic processing, we cannot exclude the possibility that severer ADHD or different ADHD subtypes might further influence acoustic processing in speech perception. Future efforts are encouraged to adopt a more fine-grained paradigm and investigate how speech processing is impaired in children with severe ADHD or with different ADHD subtypes. Moreover, neither ADHD symptoms nor neural responses are correlated with behavioral performance in the current study see . This isIn sum, the current study demonstrates that cortical activity can track different levels of speech units  during speech perception in young children with ADHD, and ADHD predominantly impairs cortical encoding of linguistic information  in speech perception.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/The studies involving human participants were reviewed and approved by the Ethics Committee of Children’s Hospital of Zhejiang University. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.CL designed the research. YY and XZ performed the research. CL, JF, YL, XZ, and YG analyzed the data. CL and YG wrote the manuscript. All authors contributed to the article and approved the submitted version.


Between-group comparisons showed no significant difference in the reporting of Attention Deficit Hyperactive Disorder characteristics, Oppositional Defiance Disorder characteristics, Autistic-Like Traits, and executive function, regardless of diagnostic state. Multiple regression analyses indicated that these personality characteristics and executive functions were associated with the perception of the reward system helpfulness. However, this pattern was qualified by both the type of hot executive function challenged (significant for Regulation not Inhibition) and whether the child had an FASD diagnosis. Thus, a dimensional approach may strengthen our understanding of the child’s classroom experience and help overcome barriers to effective intervention and support.Possession of characteristics related to Attention Deficit Hyperactive Disorder, Oppositional Defiance Disorder, and Autism Spectrum Disorder in children prenatally exposed to alcohol contributes to challenges within the diagnostic pathway for Foetal Alcohol Spectrum Disorder (FASD). The presentation of these characteristics, though problematic for the children affected, may not result in referral for diagnosis; focusing on diagnostic thresholds masks the dimensional nature of these characteristics. Children with traits which are undiagnosed may not receive effective support and are often identified as exhibiting challenging behaviour. In the UK, children with undiagnosed Special Educational Needs (SEN) are more likely to experience school exclusion. Common across each condition are challenges to executive function associated with emotional regulation (hot-executive function). This study explored the relationship between characteristics of Attention Deficit Hyperactive Disorder, Oppositional Defiance Disorder, Autistic-Like Traits, and hot executive functions on the helpfulness of reward-based interventions for children with suspected or diagnosed FASD. Data were collected online using caregiver referral questionnaire screeners for each measure  for children aged 6–12 years with suspected or diagnosed FASD ( Foetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder resulting from prenatal alcohol exposure, (PAE) . As a teDiagnostic pathways for FASD are inconsistent and patchy due to the historic lack of UK legislation. This is complicated further for clinicians by the lack of physical indication of FASD for the majority of those affected (present in less than 10%) and a reliance on confirmation of alcohol consumption during pregnancy, which is often lacking due to stigma or fear of ramifications. This can result in unpredictability in receiving a diagnosis, or the correct diagnosis ,5,6. A rThe possession of characteristics associated with Attention Deficit Hyperactive Disorder (ADHD), Oppositional Defiance Disorder (ODD), and Autism Spectrum Disorder (ASD) in children prenatally exposed to alcohol contributes to challenges within the diagnostic pathway for FASD. The high prevalence of FASD co-occurring with ADHD, ODD, and ASD can complicate the presentation of FASD, leading to missed or misdiagnosis . Lack ofRecent research indicates that pupils with neurodevelopmental difficulties are more likely to experience school exclusion . The posUnidentified Special Educational Needs (SEN) is a problem associated with school exclusion. With 55% of those permanently excluded, the identification of SEN only occurred during the exclusion period . This meDue to lack of physical features associated with FASD, the first indication can be through the presentation of behaviour displayed by the child. These are behaviours which when misunderstood can become problematic within the classroom. Thus, many teachers may have taught students with FASD without knowing. The uneven developmental profile of FASD gives rise to the need for appropriate support to access Key Stages of the English National Curriculum . Though Though there is an increase in the recognition of the conditions by clinicians, teachers, and caregivers , the relWhen school systems throw up difficulties for children and the child’s behaviour is not recognised by practitioners as potentially being characteristic of a clinical condition, or indeed the child lacks possession of a formal diagnosis of any SEN condition, the narrative of ‘problem’ quickly emerges . ConsequThose prenatally exposed to alcohol (PAE) can struggle to access diagnostic services for FASD , not leaWhilst understanding behaviour is important when supporting children in the classroom, the focus on diagnostic threshold to provide understanding can be problematic, as (1) lack of diagnosis does not mean lack of impact, and (2) long waiting lists for assessment mean a lack of interim support whilst waiting.Although clinical assessments, including cognitive tests, provide robust evaluation of the child’s difficulties, caregiver reports are required in identifying thresholds for referral for clinical assessment. However, such measures can be seen as problematic. Social cognition of caregivers is required to interpret the behaviour and affective expressions of their children, raising concern for a ‘halo effect’ in reporting ; an uninConventionally, the assessment within neurodevelopmental conditions often leads to a focus on diagnostic thresholds for each independently co-occurring condition, missing the overlap across different conditions, along a spectrum of characteristics. The view through a diagnostic lens may complicate the assumption of effective interventions designed to support those affected . When inThe focus on diagnostic threshold assumes a homogenous approach to understanding the cognitive and behavioural characteristics of a heterogeneous population . A transFASD, ADHD, ODD, and ASD are known to share similarities in patterns of challenge to executive function ,21,22,23The effect of age and gender on each of these conditions when they co-occur is uncertain. The effects of ADHD may reduce with age ; howeverwithin undiagnosed groups. Lack of diagnosis for neurodevelopmental conditions can occur either because of (1) lack of referral for assessment (unassessed), (2) possession of characteristics may not reach a referral threshold , or (3) possession of characteristics when assessed by a clinician do not meet diagnostic criteria . Given the prevalence of SEN diagnosed during school exclusion periods, it is important to understand the effect of challenges to EF along the continuum of characteristics associated with clinical conditions, regardless of diagnostic state. This is especially important when considering interventions aimed at shaping positive behaviour to promote classroom inclusion.Conventionally, clinical EF research focuses on differences between clinical groups and typically developing groups; there is little insight into the impact of challenge to EF Challenge to psychological processes associated with characteristics of ADHD, ODD, and ASD, regardless of diagnosis, may pose an elevated risk of anti-social responses to rewards and consequences. The implications of this have been found in the school-exclusion-to-prison-pipeline , which iBehaviour change mainly requires inhibiting and regulating undesired behaviour to shape desirable behaviour; inhibitory control and regulation are key executive functions . If in aShaping behaviour within school is often performed using reward-based incentive models which carry a social and moral common ground to encourage desired positive behaviour . Reward For those with ODD, independent of ADHD, challenges in both hot and cold EFs have shown implications toward reward-related abnormalities in theories of anti-social behaviour development, related to increased risky decision-making and slower speed of inhibitory response . There iAdopting a dimensional-transdiagnostic approach to understanding the impact of shared characteristics of multiple conditions along the continuum of diagnostic measurement, from sub-referral to clinical diagnosis, may help understand how daily functioning may be challenged, regardless of diagnostic status.Children with undiagnosed FASD may not receive effective support and are often identified as exhibiting challenging behaviour. A global prevalence study indicated that those with FASD are represented 10–40 times higher than the general population in special education [As hot executive function is important to the effectiveness of reward-based behaviour-shaping interventions, then it is important to understand the effect when EF is challenged. Given the prevalence of overlap between ADHD, ODD, and ASD in children with FASD, exploration is required into the relationship between challenges to hot executive function and co-occurring ADHD, ODD, and ALT characteristics for those with FASD, regardless of diagnostic state of any of these conditions. Given that research has shown that increased practitioner awareness of these characteristics beyond any diagnostic label may lead to more effective classroom support for the child, this may lead to reduction in exclusion .The evidence suggests that reward systems may be problematic for children with an FASD diagnosis. This study, employing caregiver ratings, aimed to examine the relationships between ADHD, ODD, and ALT characteristics and the child’s experience of reward systems. It further asks whether these relationships may be influenced by individual differences in emotional regulation and inhibition, and in turn, whether this mediation is affected by the FASD diagnostic status of the child.The prediction for this study is that variability in hot executive function will mediate the observed relationship between characteristics of ADHD, ODD, or ALT and the experience of rewards. This mediation in turn may be affected by FASD diagnostic status.a priori power analysis was conducted using G*Power. Prior research [n = 53. This value was derived from a G*Power analysis, selecting regression analyses with 5 predictors, 3 of particular interest, and 2 co-variates.To ascertain the sample size, an research  has typi2 = 3.36X, p > 0.05. However, the proportions with an FASD diagnosis did differ: 2 = 6.403X, p = 0.011. This indicated that a greater proportion of caregivers whose child did not have an FASD diagnosis failed to complete the survey. The F test analysis comparing the age of the children whose caregiver completed the survey, versus those who did not complete the survey after recording their child’s age, did not differ significantly: F  = 1.354, p > 0.05.Three hundred and thirty-six participants were initially recruited to take part in the online study using purposive sampling, based on being parents or carers (age 18 and above). The eligibility criteria for the study was parents and carers (caregivers) of children aged 6–12 years with suspected or diagnosed FASD. Recruitment was via National FASD and FASD Hub Scotland online support groups and associated networks. The online survey was made available to participants from April 2022 until September 2022. Only surveys where all questionnaires had >90% completion rates were eligible to be used within the study. In addition, an incomplete response to the age, gender, and FASD diagnosis status also led to exclusion. One hundred and twenty-one completed surveys were used to create the sample for the analysis, exceeding the G*Power recommendation. Chi-square comparison of the sample of caregivers who completed the survey, versus those who did not, indicated no difference in the gender proportions: 2 = 2.547X, p > 0.05.The sample included 67 children  with diagnosed FASD . A total of 54 children  made up the suspected FASD group . Chi-square analysis of the gender proportions in the two FASD diagnostic groups indicated that the proportions of boy and girls did not differ across the two groups, 2 = 13.267X, p < 0.001. Children in the FASD Diagnosed group were more likely to have co-occurring diagnoses.In the FASD Diagnosed group, 47 of the children were reported as having a co-occurring diagnosis of ADHD, ASD, or ODD. In the FASD Suspected group, 20 of the children were identified as having a co-occurring diagnosis of ADHD, ASD, or ODD. Chi-square analysis revealed that the proportion of children with a co-occurring diagnosis did differ in the two FASD groups, The study utilized a cross-sectional quantitative non-experimental design. An online questionnaire via the Qualtrics online platform  was used to obtain the data. Data were collected through caregiver ratings of characteristics associated with ADHD, ODD, and ALTs, and ratings of the hot executive functions, regulation, and inhibition. Caregiver ratings of the helpfulness of rewards for their children were also collected. Diagnostic status related to FASD, ADHD, ODD, and ASD was collected. The online questionnaire presented measures of: EF using the Childhood Executive Functioning Inventory, (CHEXI) ; ALTs usA number of analyses were performed to understand the interactions between the variables and how those relationships were associated with the helpfulness of rewards see . Due to For the main moderated mediation analysis, the predictor variables were scores from the ADHD, ODD, or ALT measures. The outcome variable was ratings of the helpfulness of reward systems in schools. Given that the prior literature indicated a relationship between ADHD, ODD, ALT, and challenge to executive function, the score of executive functions (regulation or inhibition) was used as a mediator to understand its indirect effect in the relationship between the characteristics and rewards. Though the literature indicated a relationship between traits and executive function, it was possible that having an FASD diagnosis may account for any variance in any indirect effect found, and so the observed variable FASD Diagnosis (suspected or diagnosed) was used as a moderator on the indirect effect. Covariates were age and gender within all the analyses, due to prior research indicating their association with ALT and ADHD characteristics.The survey content began with a Participant Information form which obtained informed consent prior to undertaking the study. Participants were informed of their rights of withdrawal, anonymity, and data storage security. A Participant Debrief sheet, including how to access further support on FASD, ASD, ODD, and ADHD was made available at the end of the survey. Caregivers answered demographic questions related to their child, which included age, gender, school experience, and diagnostic status. Questions were positively worded and positively scored to reduce the risk of bias in reporting from a potential negative halo effect.Three questionnaires were employed to measure caregiver reporting of variability in ALTs, (AQ-Child) , ODD andThe CHEXI  is a ratThe AQ Child is a parent-report questionnaire conventionally used to measure the expression of ALTs in children aged 4–11 years . Higher The Vanderbilt ADHD diagnostic parent rating scale is conventionally used as a screening tool to help in the diagnostic process of ADHD , in children aged 6–12 years . It has The Qualtrics survey asked 4 questions, using a 4-point Likert scale to measure parents’ observations of how helpful rewards were for their child: “never”, “occasionally”, “often”, “very often”. Three of the questions asked about helpfulness of rewards in different contexts: “instant” i.e., sticker for good work there and then; “time-lapse” i.e., certificate at end of week; and “recognition in comparison to others” i.e., certificate for highest attendance. The fourth question asked about the helpfulness of rewards overall. Cronbach’s alpha for the measure of the helpfulness of rewards was found to be marginally acceptable (α = 0.68).Ethical approval for the study was granted by the Department of Psychology Postgraduate Ethics committee at Northumbria University (Reference number-46032). Links to the survey were sent to the support groups and posted online. A copy of the information sheet and informed consent was sought at the start of the survey. Participants were then asked to complete the demographic questions, general questions, and the questions from each of the behavioural checklists. Questionnaire items were presented individually onscreen, thus not only ensuring anonymity but also reducing any acquiescent response biases. After completing the survey, participants were debriefed and provided with the opportunity to withdraw their data, if they so wished. The survey took approximately 25 min to complete. Where participants emailed expressing interest in the results, they have been advised that a user-friendly version will be made available. Follow-up analysis is intended to explore with the participants the direction of future research.n = 121) missing data from each measure of ADHD, ODD, ALT, and EF were replaced with average scores.Analysis on the total sample was performed to identify incomplete surveys. Any survey which contained >10% of unanswered questions from a questionnaire was removed from the data collection. In addition, surveys which omitted responses to either age, gender, or FASD diagnosis status were also removed. In the final sample of respondents  were carried out. To understand the relationship between ADHD, ODD, ALT, and executive function, mediation analyses using Hayes PROCESS Model 4 [The data were initially reported in terms of descriptive statistics of two groups, FASD Diagnosed and FASD Suspected, in measures of ADHD, ODD, ALT, EF and helpfulness of reward systems. Subsequently, one-sample  Model 4  was const-tests was carried out for each of the measures, comparing their distributions to the mid-point of each scale.ps < 0.05). This indicates that for both groups there were challenges across all of the trait characteristics and in both hot executive functions  = 2.173, p > 0.05. For the VADPRS–ADHD Combined measure, the Group factor was not significant: F  = 1.778, p > 0.05. For the VADPRS–ADHD Inattention measure, the Group factor was not significant: F  = 3.742, p > 0.05. For the VADPRS–ADHD Hyperactivity measure, the Group factor was not significant: F  = 0.435, p > 0.05. For the CHEXI Regulation measure, the Group factor was not significant: F  = 0.375, p > 0.05. For the CHEXI Inhibition measure, the Group factor was not significant: F  = 1.254, p > 0.05. Finally for the reward system ratings, the Group factor was not significant: F  = 0.661, p > 0.05.To directly compare the possession of the traits, hot executive functions, and reward system experience between the two groups, a series of ANCOVAs was carried out with Group as the factor. In the comparison of ODD trait possession, the Group factor was not significant: F  = 1.87, Thus, across all these analyses, there were no significant differences between the two groups in the level of trait possession, hot executive function, and the experience of reward systems.The next analyses investigated the partial correlations between the trait measures, hot executive measures, and the reward system helpfulness. The partial correlations are shown below in The final analysis looked at the interaction of the relationships between all observed variables; the traits, ADHD-Combined, ADHD-Inattention, ADHD-Hyperactivity, AQ, ODD; the hot executive functions, regulation and inhibition, and diagnostic status, FASD Diagnosed, and FASD Suspected see , throughThe explicit rationale for the analysis is shown immediately below for ADHD-Combined, including tables of the model results where regulation is a mediator . This isa path showed that ADHD-Combined had a significant effect on Regulation, and that neither age nor gender were significant in this relationship . The b path showed a variety of significant and non-significant results (see b1) was not significant, the relationship between FASD diagnostic state and rewards was significant (b2), and the interaction between Regulation and FASD diagnostic state had a significant effect on rewards (b3) (unadjusted estimate R2 = 0.045 p = 0.0197). There was no effect from age and gender in this model .In the model for ADHD-Combined, there was no direct relationship between ADHD-Combined and rewards (c’ path). The ults see . Here, tab3) found a significant indirect effect on the relationship between ADHD-Combined and rewards, which was conditional on the interaction between regulation and FASD Diagnostic state . This indicated that moderated mediation was occurring, and that from the observed variables the indirect effect of regulation was conditional on the FASD diagnostic state. The probe into the conditional indirect effect (ab1 + ab3W) showed that the conditional effect was significant in the FASD Diagnosed group  but not in the FASD Suspected group , will increase the score on the helpfulness of rewards by 0.499 (ab3), across the FASD diagnostic state. The results showed that the conditional indirect effect (moderated mediation) is significant in the FASD Diagnosed group not for the FASD Suspected group, increasing the effect on the score by 0.510. This indicates that the effect of ADHD-Combined on the helpfulness of rewards may is come indirectly via the interaction between FASD diagnostic state and regulation.The model indicates that when analysing the moderating effect of FASD diagnosis on the indirect effect of regulation in the relationship between traits and rewards, the interaction between regulation and FASD diagnosis changes the significance of the statistical effect. It suggests that an increase in regulation score by one unit, related to an increase in the ADHD-Combined score  was conditional on FASD diagnosis (b3). These results indicate a conditional indirect effect related to a diagnosis of FASD, rather than caused by it; for this group, rewards are more unhelpful when they have challenges to regulation which are related to challenges associated with characteristics of ADHD, ODD, or ASD.For all the models there was no direct relationship between the trait and the reward system, whether regulation or inhibition was the mediator in the model. The results from each moderated mediation analysis showed that there was no significant direct path X-Y, nor in the The consistent result in each model was the interaction between regulation and FASD status having a significant indirect effect on the relationship between trait and reward, and the interaction between inhibition and FASD status being non-significant. The lack of moderated mediation when inhibition was in each model indicates that regulation, not inhibition, may be influencing the effect. The results shown in The findings suggest that the possession of ALT, ODD, and ADHD characteristics were not significantly different in their intensity across the FASD Suspected and FASD Diagnosed groups. Critically, in the perceptions of the relationships between these traits and the child’s experience of rewards, the role of Regulation differed between the groups, only being significant for the FASD Diagnosed group.The aim of this non-experimental study was to understand how the relationship between hot executive function (regulation and inhibition) and characteristics of ADHD, ODD, and ALT impacts upon the helpfulness of reward-based behaviour-shaping interventions for children with FASD. Using caregiver reporting questionnaire measures, we assessed the variability in ADHD, ODD, and ALT characteristics; hot executive function; and the experience of rewards for children with FASD, both suspected and diagnosed. The study addressed the research question of how hot executive function mediates the relationship between characteristics of ADHD, ODD, and ALT and the experience of reward-based behavioural systems in school for children with FASD, and the extent to which this mediation may be dependent on the child having an FASD diagnosis.The caregiver ratings across each of the ALT, ODD, and ADHD measures indicated a significantly elevated distribution of scores. This was also the case for the hot EF measures. Given that in all the trait and EF scales, higher scores indicate challenges or difficulties, then this sample of children is evidencing high levels of behaviour and emotional challenges.regardless of their diagnostic status, are likely to encounter challenges within and outside of the classroom environment.A group comparison, contrasting the FASD Diagnosed and FASD Suspected groups, found no difference in the ratings of ADHD, ODD, ALT, EF, and reward helpfulness. This lack of difference in the possession of traits occurred despite the two groups significantly differing in the frequency of their co-occurring diagnoses. This finding, regardless of FASD diagnostic status (suspected and diagnosed), resonates with the suggestion that those with suspected FASD experience similar challenges to those with a diagnosis ,7. ImporMultiple regression, using moderated mediation analyses (Hayes PROCESS Model 14) , indicatThe significant results from the moderated mediation analyses tell us a story of how the interaction of these measured variables is important for the helpfulness of rewards for children with FASD. However, as heeded by Hayes , they arThese findings support the argument that a dimensional approach, examining variability in ODD, ADHD, and ALT in the absence of a diagnosis, may strengthen our understanding of the child’s classroom experience.Caregivers reporting their children as high along the continuum of measurement for regulation and inhibition, regardless of diagnostic state for any condition, supports the call to move away from the reliance on diagnostic state to understand the challenge to daily function faced by children who possess characteristics associated with diverse neurodevelopmental conditions ,20.The results from the caregiver screening questionnaires provide a good indication of the variability across the pre-diagnosed end of the dimension, highlighting the value in the caregiver’s assessment of challenges faced by their child. The higher frequency of diagnosed co-occurring conditions in the FASD Diagnosed group provides a greater confidence in the variability of characteristics at the diagnosed end of the dimension and could account for the significant findings for this group in the moderated mediation analyses.The moderated mediation analysis supports the importance of a dimensional-transdiagnostic approach in understanding how challenges in daily functioning may shift based on context. This analysis highlights that, though both regulation and inhibition are challenged, in the context of rewards it is probably the effect coming from emotional and behavioural regulation, not inhibition, which leads to rewards being unhelpful. In this context, challenge to regulation was a consistent pattern regardless of diagnostic state. This is an important factor for when practitioners are selecting interventions to shape behaviour within the classroom.Challenge to psychological processes in the form of hot executive function may increase the risk of anti-social responses to reward and consequence. These findings may be of interest in the context of the youth justice system, where young people with ADHD, ASD, and FASD are over-represented, many of whom may have no diagnosis . The heaIt should be understood that challenges in emotional and behavioural regulation may be important when considering reward systems for children with FASD. Focusing on the challenge to regulation processes, rather than the diagnosis status, may help educational practitioners when selecting interventions to encourage positive classroom behaviour ,9,17.Caregiver assessment without other measures such as cognitive tasks limit the findings of this study to the caregiver’s perception and social cognition. However, concerns regarding bias known to be associated with caregiver reporting of challenging behaviour of their children   were addAs indicated previously, latent variables uncontrolled for in this non-experimental study could account for some of the variance observed and therefore the results from this study should be inferred as indicative rather than definitive.The data does not indicate the child and caregivers experiences of the diagnostic pathway, so we cannot assess whether this influenced their ability to interpret their child’s behaviours. The national inconsistency across the UK in diagnostic pathways and subsequent support received within and beyond the assessment process  makes itGiven that behaviour-shaping interventions are sensitive to the environment in which they are performed , the infThough the caregiver measures used in this study have been found to have good reliability, further study would benefit from understanding the psychological mechanisms which are associated with these co-occurring characteristics. Performing cognitive tasks  to compare the findings in relation to reporting by caregivers, non-clinical, and clinical professionals could provide a more robust understanding of the psychological mechanisms underpinning the challenges experienced .Welcome advances in theoretical models that aim to improve support for the most vulnerable school children, such as trauma-informed approaches , may go Educational approaches specific to children with FASD are emerging in the UK, with information and training for educators which have been developed in conjunction with those affected by FASD; however, there have been limited empirical studies involving practices towards FASD in educational settings . As a reIncorporating these approaches, a mixed-method study could help to explore how considerations of psychological mechanisms related to characteristics associated with neurodevelopmental conditions such as ADHD, ODD, and ASD can present in the classroom. Providing psychological underpinning may improve the understanding of behaviour for those with undiagnosed SEN, reducing the reliance on assumptions of causes of behaviour . It may Working collaboratively with children, their families, schools, and FASD organisations would provide the potential for co-designed interventions which may empower the FASD community.This study has found executive function, in the form of emotional and behavioural regulation, to be an important variable to be considered when using reward-based behaviour-shaping strategies. It has reflected upon how a dimensional approach to understanding the characteristics of co-occurring neurodevelopmental conditions has the potential to enhance understanding and support for those with FASD, an area of improvement as recommended in the NICE guidelines . It high


Introduction: The Qinghai–Tibet Plateau is one of the last terrestrial environments conquered by modern humans. Tibetans are among the few high-altitude settlers in the world, and understanding the genetic profile of Tibetans plays a pivotal role in studies of anthropology, genetics, and archaeology.Methods: In this study, we investigated the maternal genetic landscape of Tibetans based on the whole mitochondrial genome collected from 145 unrelated native Lhasa Tibetans. Molecular diversity indices, haplotype diversity (HD), Tajima’s D and Fu’s Fs were calculated and the Bayesian Skyline Plot was obtained to determining the genetic profile and population fluctuation of Lhasa Tibetans. To further explore the genetic structure of Lhasa Tibetans, we collected 107 East Asian reference populations to perform principal component analysis (PCA), multidimensional scaling (MDS), calculated Fst values and constructed phylogenetic tree.Results: The maternal genetic landscape of Tibetans showed obvious East Asian characteristics, M9a (28.28%), R (11.03%), F1 (12.41%), D4 (9.66%), N (6.21%), and M62 (4.14%) were the dominant haplogroups. The results of PCA, MDS, Fst and phylogenetic tree were consistent: Lhasa Tibetans clustered with other highland Tibeto-Burman speakers, there was obvious genetic homogeneity of Tibetans in Xizang, and genetic similarity between Tibetans and northern Han people and geographically adjacent populations was found. In addition, specific maternal lineages of Tibetans also be determined in this study.Discussion: In general, this study further shed light on long-time matrilineal continuity on the Tibetan Plateau and the genetic connection between Tibetans and millet famers in the Yellow River Basin, and further revealed that multiple waves of population interaction and admixture during different historical periods between lowland and highland populations shaped the maternal genetic profile of Tibetans. East Asia is one of the most densely populated regions in the world, with rich genetic, cultural, and linguistic diversity. Paleogenomic studies have revealed a complex demographic history of migration, interaction, and admixture in East Asia , and theTibetans belong to the Tibeto-Burman language group in the Sino-Tibetan language family. Tibetans are among the few high-altitude settlers in the world, and the adaption of high altitude in Tibetans can be attributed to archaic introgression and natural selection . The TibMitochondria are indispensable organelles for energy production in eukaryotic cells . The mitDiverse genetic ancestral sources and a complex demographic history of Tibetans have been revealed by previous studies . AlthougThis study, which included peripheral blood samples from 145 unrelated healthy Tibetans, was carried out via health examination in August 2016 in Lhasa , China. Our study was reviewed and approved by the Medical Ethics Committee of Jinzhou Medical University (JZMULL2016010) and followed the recommendations provided by the Helsinki Declaration. All Tibetan participants were sampled after obtaining verbal and written informed consent. To keep the representativeness of the samples, the Tibetan participants in this study were unrelated indigenous people who had lived in the sampling place for at least three generations, and they declared that no migration events had occurred in their family history.® Mag Blood DNA Small Extraction Kit (LD764), which is based on magnetic bead-based extraction, following the manufacturer’s instructions. The quantity of gDNA was measured using a NanoDrop ND-1000 instrument , according to the manufacturer’s instructions. In consideration of the requirements of downstream processing, the gDNA was normalized to 1 ng/μL and stored at −20°C until amplification. DNA libraries were constructed using an Eltbio® WHO_MT Kit (LD640), according to the manufacturer’s instructions. PCR amplification was performed in a final volume of 30 μL containing 10 ng of gDNA, 5 μL of RealCapChrMT Mix, and 10 μL of 3 ×EnzymeHF. Total reaction volumes were adjusted with nuclease-free water. The PCR conditions were as follows: enzyme activation for 3 min at 98°C, 13 cycles of 20 s at 98°C and 4 min at 58°C, seven cycles of 20 s at 98°C and 1 min at 72°C, and extension for 2 min at 72°C, followed by a 10°C hold. After purification, a second round of PCR amplification was performed to introduce adapters and barcodes. The reaction volume (30 μL) comprised 18 μL of purified products from the first round, 10 μL of 3 ×EnzymeHF, 1 μL of primer mix, and 1 μL of barcode mix. The PCR conditions were as follows: enzyme activation for 2 min at 98°C, six cycles of 15 s at 98°C, 15 s at 58°C and 15 s min at 72°C, and extension for 2 min at 72°C, followed by a 10°C hold. After purification, the libraries were pooled to a final concentration of 20 pM. Sequencing was performed on the Illumina HiSeq X Ten platform  with the corresponding Reagent Kit (PE150).DNA extraction was performed using the EltbioThe sequence data obtained from the Illumina HiSeq X Ten platform  were automatically analyzed by base recognition and converted into the original sequences in the FASTQ format. First, we removed redundant primers and indexes from the initial offline data using Cutadapt v3.2 software . Second,http://www.phylotree.org/tree/index.htm) and reconfirmed using the updated query engine (SAM2) built into EMPOP  per individual. The scores of the mean quality and per sequence quality were over 30, implying that the quality of the sequencing data was good . The valThe mtDNA haplogroup information of 145 Lhasa Tibetans is shown in The results of PCA and MDS are shown in The results of pairwise Fst genetic distance among East Asian populations are shown in Additionally, we constructed a phylogenetic tree of East Asian populations and showed the maternal genetic makeup of different people in To estimate the population size fluctuation over time, BSPs were performed for Lhasa Tibetans . PreviouTwo root maternal haplogroups (M and N) were distributed mainly in East Asians. In this study, haplogroup M was found in 56.55% and haplogroup N in 43.44% of Lhasa Tibetans, and the maternal genetic landscape of Tibetans showed obvious East Asian characteristics, where M9a (28.28%), R (11.03%), F1 (12.41%), D4 (9.66%), N (6.21%), and M62 (4.14%) were the dominant haplogroups. M9a is the most prevalent maternal haplogroup in Tibetans, with frequencies ranging from 12.26% to 29.24% . Our resHaplogroup D4 is prevalent in East Asia, especially in northern East Asian populations, and has the highest frequency in the modern Han population. It may have originated in northern China and may be associated with millet famers in the YRB, and the distribution of haplogroup D4 in East Asia could be attributed to the expansion of ancient agriculture . HaplogrHaplogroup F1 is frequent in southern and southwestern China . F1g is In this study, we found that some Tibetans belong to haplogroups N and R, which are the main macrohaplogroups in Eurasia. Studies of ancient DNA have found haplogroups N and R in ancient populations related to the Lower Xijiadian culture , Majiayao culture , Xiaohe culture , Afanasievo culture , Boisman culture , and Ganj Dareh  , indicatThese sporadic lineages also revealed population interaction and admixture between Tibetans and adjacent populations. Haplogroups A, B, and C are some of the most common haplogroups in northern and eastern Asia . HaplogrIn summary, this study supported the conclusion that the maternal genetic history of Tibetans can be characterized as long-term matrilineal continuity with frequent interactions between lowland and highland populations . PrehistThis study investigated the whole mitochondrial genome of 145 Lhasa Tibetans and found that the maternal genetic landscape of Tibetans showed obvious East Asian characteristics, and M9a (28.28%), R (11.03%), F1 (12.41%), D4 (9.66%), N (6.21%), and M62 (4.14%) were the dominant haplogroups. This study further revealed long-time matrilineal continuity on the TP and a genetic connection between Tibetans and millet famers in the YRB and further supported the North China origin of the Sino-Tibetan language. We found that multiple waves of population interaction and admixture during different historical periods between lowland and highland populations shaped the maternal genetic profile of Tibetans.


Attention deficit/hyperactivity disorder (ADHD) often co-occurs with substance use disorders (SUD). Together, these disorders are associated with significantly more burden for patients and society, than each alone. Patients with SUD and underlying ADHD have more complex SUD and have more poly-substance use compared with SUD patients without ADHD. A correct identification of ADHD in adult and adolescent individuals with SUD remains important regarding treatment, treatment effectiveness, and treatment retention.Several screening tools are available and have been validated in individuals with ADHD and comorbid SUD. It is highly recommended that these are used routinely, followed by an ADHD diagnostic process initiated as soon as possible. While several treatment options are accessible, randomized controlled trials show only limited effect sizes of standard pharmacotherapy in adult and adolescent ADHD patients with comorbid SUD. Simultaneous and integrated treatment, with a combination of pharmacotherapy and psychotherapy and for both ADHD and SUD, should preferably be initiated.We present an overview of the current international guidelines on screening, diagnosis and treatment of ADHD adults and adolescents with comorbid substance use disorders.None Declared


In the UK, Attention Deficit Hyperactivity Disorder and waits for assessment, diagnosis, and treatment are all growing problems. This study set out to gather service users’ suggestions as to how one specialist ADHD service could improve the experiences of people on their waiting list. Following a semi-structured focus group, an inductive thematic analysis of data yielded three themes: (1) support for psychoeducation in principle, (2) psychoeducation regarding the wider, holistic impact of ADHD, and (3) suggested structures and approaches, as well as (4) a set of general feedback that could inform service developments. Service users supported the notion of psychoeducation sessions to inform people on the waiting list about the wide range of potential impacts of ADHD, the most common psychiatric comorbidities, some potential coping strategies they could try, and the service they could ultimately expect to receive. Some form of one-to-one telephone support was also advocated, primarily to address their concerns about the lack of individualisation group psychoeducation could offer. The potential benefits of these suggestions combined with the low risk of adverse effects makes group psychoeducation a worthwhile waiting list initiative. However, as with any service development, it should be piloted and evaluated before being termed treatment as usual for the service. Attention deficit hyperactivity disorder (ADHD) is an early onset neurodevelopmental disorder that persists into adulthood in about 50% of cases . EstimatThree somewhat overlapping systematic reviews into non-pharmacological interventions for adult ADHD were published in 2020 by Nimmo-Smith et al.  Fullen ePsychoeducation is the provision of information regarding a patient’s disorder, its cause and related dysfunctions and deficits . It is iHirvikoski et al.’s RCT found psychoeducation to be more effective than ‘treatment as usual’ in increasing knowledge about ADHD and global life satisfaction . More thWhat is even less clear from a brief search of the literature is precisely what service users feel should be covered in an adult ADHD psychoeducation package and what benefits they expect to derive from attending. In the UK, specialist adult ADHD services are under considerable pressure with lengthy and rising waiting lists . This haThis MSc dissertation project employed a qualitative service evaluation design, so that an understanding of the subjective experience of participants could be gained ,14. EthiPurposive sampling was utilised as only those with a diagnosis of ADHD within the Sheffield ADHD service, that had capacity, and were English-speaking were contacted . Those tPotential participants were initially contacted by post and/or telephone between Dec 2021 and February 2022 to inform them about the study. Once sufficient interest had been expressed to form a meaningful focus group , copies What do you know about psychoeducation as an intervention?How do you think you would benefit from being educated more thoroughly on your condition?What topics do you think should be included within a psychoeducation intervention?Is there anything else that anyone would like to discuss regarding the ADHD service or psychoeducation?Due to time and resource constraints, a single online semi-structured focus group consisting of four males and one female was held by the researcher (who was independent of the service). Mindful of the challenges that group work might pose to the participants with ADHD, the focus group began with a briefing that included ground rules and the expectation that everyone would be supported to both express their views, but also listen to those of others. The Zoom platform  was alsoSupplementary questions were asked by the researcher as appropriate, with the focus group lasting a total of 46 min after which a short debrief was conducted. A nurse consultant from the service (who had previously reviewed the questions) was present for the brief and debrief but not the main discussion to encourage candour. They were, however, constantly available in a separate Zoom break-out room in case of participant distress.(1)Familiarising self with data: the transcript was read repeatedly to become immersed in the content.(2)Generating initial codes: important statements were highlighted, and the transcript re-read to confirm all key phrases had been selected.(3)Constructing themes: the key statements were colour coded, to represent initial sub-themes. Preliminary names were given, and the transcript reviewed to ensure all relevant statements had been included.(4)Reviewing themes: the homogeneity of each set of codes was considered and some statements were moved between themes until they were in the theme that best described the quote. Sub-themes were also combined to create larger themes.(5)Defining and naming themes: sub-theme and theme titles were reviewed to ensure they accurately represented the source data (codes), were sufficiently distinct from each other, and all spoke to the over-arching research question.(6)Producing the report: salient quotes for each theme were selected to aid their description and to provide rationale for subsequent practice recommendations.The Zoom transcription was reviewed and corrected using the audio recording to produce a verbatim account of the discussion in Microsoft Word . An induThree primary themes, each with several subthemes, emerged from the thematic analysis: (1) support for psychoeducation in principle, (2) the need to cover the wider, holistic impact of ADHD, and (3) suggested structures and approaches. General feedback regarding the ADHD service was also gathered and anything related to the research question is presented as an additional theme, (4), to help inform the proposed intervention see .Participants acknowledged that the ADHD team was currently only commissioned to provide a diagnostic and medication initiation service. However, they had all experienced limitations and/or adverse effects of pharmacological interventions and were keen to consider psychoeducation as an augmentation strategy.“…there’s a lot of people out there that medication certainly isn’t the answer. And if we can come up with something that works instead of medication, I think it’s wonderful”.Participant 2—“I think it’s just at the minute it’s just about well, medication, but sometimes medication’s not just the answer”.Participant 3—“I think it could compliment medication as well. I think there’s, I think there’s a need to say that there needs to be the choice to have, have them both together combined”.Participant 4—Specifically, participants welcomed the potential to receive trustworthy information about their condition, perceiving this to be a means of empowerment.“I think understanding it in a broad sense to begin with is helpful. I mean, when, when I had my assessment about less than 12 months ago now, you get a lot of information that is, like medical speak. And the assessment went quite quickly in the end, or seemed to go quite quickly, so having a baseline education of it would be useful but would just be a starting point”.Participant 4—“For me, clearly more information will be great. Yeah, there’s a lot of misinformation out there there’s a lot of pseudoscience there’s a lot of things that I would like to know”.Participant 1—Overall, there was clear support for the provision of psychoeducation at an early stage in the service user’s journey.In addition to information about ADHD itself, participants stressed the need to inform users about common comorbidities.“I won’t say the ADHD is the problem, it’s the underlying issues like the anxiety, the paranoia, the confidence”.Participant 3—“I’ve had anxiety issues, since I was around 20, and I struggle I would say more with the anxiety, than the ADHD”.Participant 2—They were also concerned that users were made aware of the diverse ways that ADHD had impacted their lives.“I have a full-time job, it’s really difficult”.Participant 1—“I have a great difficulty travelling”.Participant 2—As well as how to manage the primary symptoms of both.“I would very much like, yeah, help on the [cognitive to verbal] filter”.Participant 1—“Well I’ve gone through life, and you see it in the cartoon with the devil on one shoulder angel on the other. I’m sad to say that the devil wins every time. I’ve always been told all through life that I have no [cognitive to verbal] filter”.Participant 2—“And just more mental health support, more group therapy, more thoughts on how to do anger management, how to manage yourself, even I’d take even like basic help with diet planning sometimes”.Participant 1—“Whether you put action plans in, problem solving”.Participant 3—“About managing the depression and the hyperactive side”.Participant 5—“Learn how to self-manage things”.Participant 3—Together, the participants provided helpful insights into what should be included in a psychoeducation package. Additionally, that there would be benefits to users receiving this input at an early stage of their journey through ADHD services.Participants appreciated resource constraints were driving the notion of a psychoeducation group, rather than 1:1 delivery; however, there were some reservations. Primarily, these concerned the idiosyncratic way ADHD had affected participants, and the fact that a group intervention might preclude the provision of person-centred, individually tailored information.“Everyone’s different so what works for one person won’t work for another”.Participant 1—One participant described his positive experience of (privately funded) 1:1 psychoeducation.“Like I want something that is specific, and it’s all very intense, an hour and a half session every week. However, it’s very very practical advice, you know, and it’s tailored to you, what my own process is like what my triggers are and what my strengths are really”.Participant 4—Which led the group to make a number of suggestions to ameliorate these shortcomings.“Maybe a drop in. Well, you know, you know that doesn’t cost a lot of money does it to have a drop-in centre”.Participant 3—“Somebody on the phone once a week that can answer some of these questions”.Participant 3—“Again making that a part of the service where, if someone is having a bit of a crisis time with things and they really do need to speak to someone that there is actually a number that somebody will speak to you”.Participant 2—Overall, therefore, a group intervention was supported by participants, provided sufficient attention could be paid to individual attendees.As part of the focus group, participants were given the opportunity to provide general feedback about the service, all of which was passed onto staff. Presented here are just the points that speak directly to initiating a psychoeducation group for people on the ADHD service’s waiting list.“I want to be able to know what I’m actually going to be waiting for, and what choices there are for me to be on those waiting lists”.Participant 4—“Yeah, I mean the transparency is, it’s just a blank point, basically I have no idea why I’m on the waiting list or what’s going to happen or what the programmes are or where it’s going”.Participant 1—“But for the people that are waiting for medication. Maybe a group could be okay. Because then they’re not just getting ignored”.Participant 3—Lengthy waits were a definite source of dissatisfaction but participants felt that more detailed information about the interventions, they could ultimately expect would make the wait less frustrating, hence appreciating the efforts being made with this project.“They are an amazing team, they’re trying to get, this is why you know people are here today. They are trying to, you know, do the best for the service users”.Participant 3—In the spirit of co-production , this stSupport for psychoeducation in principle: The National Institute for Health and Care Excellence (NICE) advocates group-based ADHD-focused carer support and states this need not wait for a formal diagnosis [iagnosis  p. 10).iagnosis  p. 13)..Support iagnosis , much ofiagnosis . However.iagnosisiagnosis ,23,24. SPsychoeducation regarding the wider, holistic impact of ADHD: Our participants cited anxiety as a frequently encountered problem. This is contradicted by some works of literature which found no significant association between ADHD and anxiety [ anxiety . However anxiety . Unsurpr anxiety . Help wi anxiety ,29.The wide-reaching effects of ADHD were universally recognised by our focus group participants which is again, in keeping with the literature which highlights deficits with executive functioning and more workplace absence, leading to reduced productivity and work performance and higher unemployment levels ,31. WhilSuggested structures and approaches: In the absence of direct experience of group interventions, our participants had some reservations about the delivery of psychoeducation in a group setting. These pre-conceptions focused on whether group interventions could ever really be person-centred. However, Byrne et al. found control and power over one’s own care to be integral to the concept [ concept , which C concept . Further concept ,37. It s concept  and part concept , making General feedback that could inform service developments: Waiting times for mental health services in the UK are a well-recognised issue [ed issue . Unlike ed issue . Helpfuled issue . Serviceed issue ,43. In tA psycho-education group for people on the waiting list for a diagnostic appointment should be piloted.○a detailed explanation of the service that people can ultimately expect to receive;○information regarding ADHD and the full breadth of its potential impact on individual’s functioning and quality of life;○information about the most frequently encountered psychiatric comorbidities;○low-level coping strategy enhancementThe content should include:Consideration should be given to augmenting the group intervention with some form of one-to-one telephone support, perhaps linked to periodic updates of people’s position on the waiting list.A further student service evaluation project should be devised to ascertain the impact of group psychoeducation for people waiting for specialist ADHD assessment and diagnosis. This should adopt a mixed methods approach to capture subjective and objective data.This service evaluation project was specifically contrived to provide tangible options for an ADHD service to consider as part of their waiting list management plans. Based on the views of a group of their service users, and a brief review of the relevant literature our suggestions are that:Out with these service-specific recommendations, it is clear that larger scale studies with well-matched control groups are required to add to the knowledge base and to provide additional material for a future meta review of psychoeducation initiatives specifically .This study has produced a set of tangible recommendations to improve the experience of waiting for a specialist ADHD assessment. Data were gathered and analysed by a student mental health nurse with limited experience of thematic analysis. They were, however, supervised by an experienced researcher to ensure fidelity to the cited six-stage process  was mainThe demand for specialist ADHD services in the UK is growing. Waiting for assessment, diagnosis, and treatment is at best frustrating and at worst detrimental to people’s quality of life. Group psychoeducation packages have the potential to improve people’s negative experiences of lengthy waits. These should cover a broad range of ADHD-related issues rather than having a narrow, diagnostic focus. Consideration should also be given to additional one-to-one telephone support. Any such service developments should be evaluated to ascertain their impact and inform their continuous improvement.


Bartonella and rodents from Israel’s northwestern Negev Desert. We chose to study this system because, in this region, 75–100% of rodents are infected with Bartonella at any given time, despite an efficient immunological response. In this region, Bartonella species circulate in three rodent species, and we tested the hypothesis that at least one of these hosts exhibits a waning immune response to Bartonella, which allows reinfections.Pathogens face strong selection from host immune responses, yet many host populations support pervasive pathogen populations. We investigated this puzzle in a model system of Bartonella strain, and we quantified the bacterial dynamics and Bartonella-specific immunoglobulin G antibody kinetics over a period of 139 days after the primary inoculation, and then for 60 days following reinoculation with the same strain.We inoculated captive animals of all three rodent species with the same Bartonella strain.Contrary to our hypothesis, we found a strong, long-lasting immunoglobulin G antibody response, with protective immunological memory in all three rodent species. That response prevented reinfection upon exposure of the rodents to the same Bartonella and their hosts influences the epidemiological dynamics of these pathogens in nature.This study constitutes an initial step toward understanding how the interplay between traits of  The prevalence of parasites and pathogens in their host populations is a critical ecological variable for explaining epidemiological patterns –3. For eBorrelia, and Plasmodium) are highly prevalent even in hosts with competent and efficient immune responses because the pathogens readily evolve antigenic variation that enables new strains to reinfect hosts with immune defenses that cleared prior infections  . We calcG. andersoni, G. gerbillus, and G. pyramidum with the same strain, B. krasnovii A2. We followed the bacterial dynamics and Bartonella-specific IgG antibody kinetics for 139 days after the primary inoculation, and then for an additional 60 days following reinoculation with the same strain. In parallel, we sampled the blood of three control rodents (one of each species) that were first inoculated with PBS and only inoculated with Bartonella at day 140  was a G. andersoni, which was Bartonella-negative between days 50 and 102 , 111 , 120, 139, 149, 159, 169 , and 200 d.p.i.]. In addition, four individuals had a questionable infection status at day 81 , so we bled them again at day 91 to confirm their infection status. At day 113, we also quantified the bacterial load of the single Bartonella-specific, as the control rodents remained Bartonella-negative throughout the first experimental stage (days 0–140), with no noteworthy rise in their antibody levels, whereas they developed an infection and elevated antibodies upon inoculation during the second experimental stage . However, the overall antibody response was positively correlated with overall bacterial loads . All previously infected rodents mounted a secondary immune response following the repeated inoculation, as expected for animals with immune memory. Moreover, as expected, the humoral response that ensued was more rapid  in a variety of reservoir hosts, including house mouse (Mus musculus), cotton rats (S. hispidus), and cats (F. catus), which illustrated similar in vivo bacterial dynamics, antibody kinetics, antibody-mediated clearance of bacteremia, and failures of reinfection [Bartonella adhesion to erythrocytes . Taken e below; ). Thus, G. andersoni host and one G. pyramidum host. In these individuals, Bartonella cells reappeared in the bloodstream within 30–40 days of their disappearance despite the fact that both individuals mounted strong Bartonella-specific responses upon inoculation. There are several possible explanations for this pattern of recurrence. First, it is possible that the infection had never been cleared from the blood of these two rodents, but that its level decreased below detectable levels [G. andersoni that were inoculated with the same Bartonella strain in a previous study [We observed recurrent bacteremia in one e levels . Howeverus study , never lus study ; howeverBartonella species was endothelial cells, but additional cellular niches with similar roles were later proposed, including the dermis, lymph nodes, bone marrow, liver, spleen, and the kidney . This hiding–mutating–seeding scenario that is supported by both the observed bacterial and IgG antibody dynamics, and aligns with immunological evidence from other Bartonella species [Bartonella in the host’s blood during the peaks of initial and recurrent infections, and testing the cross-reactivity of the IgG response to these two bacterial sources.A third possible explanation is that, upon first inoculation of these two rodent individuals, some bacterial cells remained in—as yet unidentified—cellular niches in host tissues, where they persisted and replicated. Only later, after the rest of the bacteria were cleared, did these latent bacteria re-enter and recolonize the blood stream. The first recognized so-called primary niche in iewed in ). This hquintana , 27, 53.mia Fig. c, n. Aft species  and long species , 50). ThS. hispidus) and deer mice (Peromyscus maniculatus), 8–15% of the hosts showed recurrent Bartonella infections [Future studies should assess how common recurrent bacteremia is under natural conditions. In natural populations of cotton rats , it is fections .B. krasnovii A2 strain elicited an efficient and protective immune response in all of the species tested. Yet, despite the similar microhabitats of G. gerbillus and G. pyramidum [G. gerbillus and G. andersoni [G. gerbillus may be more reactive than those of the two other species. This was demonstrated by the magnitude of the increases in antibody levels following reinfections compared to the primary responses, which were highest in G. gerbillus .G. gerbillus may indicate that this host is more adapted to Bartonella than the two other species. However, considering the sporadic temporal and spatial occurrence of G. gerbillus as compared to the steady occurrence of G. andersoni and G. pyramidum rodents in the natural environment [G. gerbillus faces strong selection due to infections with B. krasnovii A2 strain. Instead, assuming that Bartonella is ahead of its hosts in the evolutionary arms race, the higher bacterial loads in G. andersoni and G. pyramidum compared to G. gerbillus may indicate that B. krasnovii A2 strain is more adapted to these more reliable hosts, and can therefore better hide and/or escape from their IgG antibodies [Bartonella strains that are either locally adapted or not adapted to each of these rodent species. The aim of these studies would be to elucidate the missing links between the long-term infection dynamics, immune kinetics, and history of coevolution between these pathogens and their hosts, which is crucial information for understanding patterns of epidemiological dynamics in natural communities.Higher resistance is often observed when hosts are locally adapted to their pathogens –62. Thusironment , it is utibodies , 64. To Bartonella persists for weeks within the protected niche of host erythrocytes is consistent with their high prevalence in reservoir hosts, our finding that there is a comprehensive host serological immune response with an efficient memory leaves the puzzle of Bartonella’s pervasiveness unresolved. Future laboratory experiments with food-deprived rodents, juvenile rodents, and reproductive female rodents under predation risk should be conducted to confirm our results in communities that better represent the states of these rodent populations in nature. These experiments could address whether a comprehensive immune response against Bartonella would also develop under more challenging conditions for hosts than the seminatural conditions provided in the current experiment. In parallel, it is important to follow the changes in infection status of, and Bartonella strain composition within, the same rodent individuals over monthly intervals in the field.While the unique strategy by which Bartonella, we also suggest that other studies should be undertaken that focus on an alternative explanation for the puzzle of Bartonella’s pervasiveness, namely, the existence of genetic mechanisms that allow these pathogens to rapidly evade the well-adapted immune responses of their natural hosts. This alternative explanation is in line with the results of a longitudinal study of the dynamics of Bartonella observed in a natural population of cotton rats (S. hispidus), in which infections of the same individual hosts by Bartonella variants from different genogroups often followed one another [Considering that the studies proposed above may provide further support for the existence of a comprehensive immune response against  another , 66.Bartonella, at least three genetic mechanisms operate that could lead to rapid antigenic variation. First, contingency loci, which are hypermutable sites on specific genes, may undergo mutations that add or remove repeat units at high rates due to strand slippage during DNA replication. Although they have never been fully profiled in Bartonella, an elevated number of mononucleotide repeats in this genus, relative to other bacteria, has been noted [Bartonella revealed high rates of intragenomic recombination events that copy, delete, and hybridize the main versions of these genes with other nearby copies [Bartonella share a domesticated prophage that acts as a gene transfer agent, packaging their DNA for transduction. Gene transfer agent-mediated recombination may accelerate antigenic variation, and virulence factor evolution through the exchange of DNA between co-infecting strains in the flea gut or host tissues [Bartonella may shed light on a universal mystery—the pervasive nature of limited-term pathogens despite efficient host immune responses.Antigenic variation—when pathogen populations evolve to alter surface features targeted by the host immune system—is one of the most widely used escape strategies that allows pathogens to reinfect hosts that have developed an immune response against the original strain . In Baren noted . Second,y copies –72. Fina tissues . UnderstBartonella and their hosts influences the epidemiological dynamics of these limited-term pathogens in nature.This study constitutes an initial step toward understanding how the interplay between traits of