Estimates of the effectiveness of neurofeedback as a treatment for attention-deficit hyperactivity disorder (ADHD) are mixed.To investigate the long-term additional effects of neurofeedback (NFB) compared with treatment as usual (TAU) for adolescents with ADHD.n=41) or TAU (n=19) were followed up. Neurofeedback treatment consisted of approximately 37 sessions of theta/sensorimotor rhythm (SMR)-training on the vertex (Cz). Outcome measures included behavioural self-reports and neurocognitive measures. Allocation to the conditions was unmasked.Using a multicentre parallel-randomised controlled trial design, 60 adolescents with a DSM-IV-TR diagnosis of ADHD receiving NFB+TAU  and performance on neurocognitive tasks was faster  irrespective of treatment group.At 1-year follow-up, inattention as reported by adolescents was decreased  licence. Stimulant medication is effective in reducing ADHD symptoms in youngsters with ADHD4 and – although possibly to a lesser extent – in youngsters with combined ADHD and ASD.5 Although medication seems to be effective, there are limitations as well, such as limited knowledge of long-term efficacy and side-effects.6 Moreover, despite the persistent nature of ADHD, the majority of adolescents with ADHD discontinue stimulant medication before adulthood.7 Additions or alternatives to the current treatment as usual (TAU) to reduce ADHD symptoms further, and on a long-term basis, are therefore desirable. Neurofeedback has been suggested as a potentially effective intervention for reducing ADHD8 and ASD9 symptoms.Attention-deficit hyperactivity disorder (ADHD) is characterised by the re-occurring patterns of inattention and/or hyperactivity/impulsivity symptoms that interfere with developmentally appropriate social, academic or occupational functioning.11 and decreased beta11 activity compared with typically developing youngsters. Increased theta (4–7 Hz) is associated with lower vigilance, and decreased beta (13–30 Hz) is associated with reduced attention.12 In addition, the sensorimotor rhythm , measured above the central sulcus, has been related to behavioural inhibition.13 As neurofeedback aims to reduce ADHD symptoms such as diminished vigilance, attention and inhibition, most neurofeedback protocols train suppression of theta activity and reinforcement of beta (12–20 Hz) or SMR (12–15 Hz) with electrode placement on the vertex (Cz).10 A complete neurofeedback intervention typically comprises 20–40 training sessions.10 The effectiveness of neurofeedback as treatment for ADHD is still actively debated.Neurofeedback is intended to alter brain activity by providing feedback from electroencephalogram (EEG) activity to patients; this is expected to lead to improvements in behaviour. Overall, youngsters with ADHD show increased theta14 to non-significant when only probably masked studies are considered.15 It has been suggested that a major advantage of neurofeedback over medication may be long-term effects after treatment completion. To date there has been only one randomised controlled trial (RCT) comparing the long-term effects of neurofeedback and stimulant medication.16 This study demonstrated similar levels of ADHD symptoms at 6-month follow-up for children who had received neurofeedback (n=12) and children treated with stimulant medication (n=11). It should be noted that at the 6-month follow-up, 8 of the 12 children who had received neurofeedback had started stimulant medication treatment.16 Long-term effects of neurofeedback were found in two RCT studies: neurofeedback was more effective in reducing ADHD symptoms as reported by parents than computerised attention training up to 6 months of post-treatment as stand-alone treatment17 or add-on treatment.18Estimates of the effectiveness of neurofeedback for the treatment of ADHD range from efficacious19 but evidence on the longterm effects of neurofeedback is limited. Since the aim of neurofeedback is to induce enduring changes in brain regulation to improve behaviour, we predict long-term effects as a consequence of improved brain functioning. The aim of the current study was therefore to investigate the value of neurofeedback as a supplement to TAU for adolescents with ADHD and comorbid disorders at 1-year follow-up.In summary, neurofeedback is viewed as a potentially effective treatment for ADHD symptoms. Comparative studies of short-term effects have shown that neurofeedback training can be as effective as stimulant medication,1 diagnosis of ADHD and a full-scale total intelligence quotient (TIQ) >80 on the Wechsler Intelligence Scale for Children (WISC-III) or the Wechsler Adult Intelligence Scale (WAIS-III).21 Adolescents diagnosed with ASD ) with confirmed clinical ADHD symptoms sufficient for a clinical diagnosis were also included. ADHD symptoms were verified by a Dutch semi-structured DSM-IV-based ADHD interview for adults22 and the Mini International Neuropsychiatric Interview (MINI).24 Exclusion criteria were neurological disorders, schizophrenia and other psychotic disorders.Eligible participants were male adolescents with Dutch as their native language, aged between 12 and 24 years, with a primary clinical DSM-IV-TRn=59) or TAU only . The total drop-out and exclusion rate after randomisation did not differ for the NFB+TAU group  or the TAU group , P=0.485 two-tailed Fisher’s exact test. The participant flow diagram is presented in In total 90 adolescents were randomly assigned to the treatment groups: combined neurofeedback (NFB) and TAU , anxiety disorders (n=3), substance-related disorders (n=3), conduct disorders (n=3), learning disorders (n=5), tic disorders (n=1) and reactive attachment disorder (n=1). The final group characteristics are listed in Medication use and comorbid disorders were allowed. Comorbid disorders present in the final group at 1-year follow-up were: depressive disorders  was notified the same day whether he would receive neurofeedback treatment. Allocation to the conditions was unmasked; participants, parents, neurofeedback trainers, the outcome assessor and clinical professionals were aware of group allocations. Different individuals fulfilled the roles of outcome assessor and neurofeedback trainer. All data entry was masked to group allocation (NFB+TAU or TAU) and was checked twice by different research assistants.A multicentre parallel group study was conducted, with stratification for age group  and unbalanced randomisation to treatment (2 NFB+TAU: 1 TAU). Unbalanced treatment was applied to encourage study participation by greater odds to receive neurofeedback at study entree. The randomisation process was computer-controlled,26 predicted that a total sample size of 46 would be sufficient to detect a medium effect size (f=0.25) in a repeated measures ANOVA with two measurements, with an alpha of 0.05 and a power of 90%. In addition, a total sample size of 42 would be sufficient to detect a medium effect size (f=− 0.25) in a repeated measures ANOVA with three measurements , with an alpha of 0.01 and a power of 90%. We have followed the CONSORT 2010 guidelines27 for reporting parallel group randomised trials. This trial is registered in the Dutch trial register .Before the study, calculation with G*power version 3.1.5.128 Behavioural interventions included regular cognitive–behavioural therapy, systemic therapy and/or supportive counselling for the adolescent and/or his parent(s) (v. NFB+TAU) in the use of stimulant medication or the type of behavioural therapy received . TAU was monitored using an intervention questionnaire based on the Dutch national basic programme ADHD for children and adolescents.arent(s) . Stimulareceived .n=41). A theta/SMR training29 – a form of theta/beta training – was used, with thresholds to inhibit theta/alpha frequency bands (4–7 and 8–11 Hz), reward SMR activity (13–15 Hz) and inhibit beta/gamma (22–36 Hz) conducted on Cz. The intervention conditions are described in more detail elsewhere.30Neurofeedback training was carried out over a period of around 5 months (25 weeks), with two to three training sessions every week. Each participant was offered a total of 40 30-minute training sessions. The mean number of training sessions received was 38 (s.d.=4.43), with a minimum of 19 sessions for the adolescents in the NFB+TAU group at 1-year follow-up .The MINI:32 , with subscales for inattention and hyperactivity/impulsivity .35The ADHD rating scale, a DSM-IV-based self-report for adults36 the attention problems subscale, the externalising problems scale and total problems scale were used. Participants aged over 18 years also completed the YSR, as most of them were still attending school and living with their parents.The Youth Self Report (YSR):Primary outcome measures included the following.Secondary outcome measures included the following.37 raw scores for total processed items and total correctly processed items.The D2 Attention and Concentration Test30 total score  and the maximum correctly recalled row length.The digit span backwards (DSB):39 for total execution time of the colour-word card and interference time.The Stroop Color-Word Test40 for the raw total correct, total moves, initiation time, execution time and total time were calculated.The Tower of London (TOL) test:Before the start of the study, approval was obtained from the Medical Ethics Committee for Mental Health Institutions in The Netherlands (Ref. no: NL 24776.097.08 CCMO). The study took place in three centres for child and adolescent psychiatry  in the south of The Netherlands. After the study was explained , written informed consent was obtained from each participant. For those younger than 18 years, parents also provided written informed consent.41 and Autism Spectrum Quotient42) were not included because of the low response rate (48%) of the total randomised sample at the follow-up measurements.At pre-intervention, participants were seen on three occasions for the administration of behavioural questionnaires, neurocognitive tests, the WAIS or WISC intelligence test and EEG measurements, where applicable medication was taken as normal on the day of assessment. Interventions took place between December 2009 and July 2012. The duration of the intervention period was approximately 25 weeks. Data collection continued until August 2013. Post-intervention and 1-year follow-up assessments included behavioural questionnaires and neurocognitive tests for all 60 participants. There were missing data for the D2 Attention and Concentration Test (two participants), Stroop test (two participants), TOL (one participant) either because of administrative problems or because the participant refused to complete the task. Parent reports (Child Behavior Checklistχ2) with Fisher’s exact correction. Attrition analyses for behavioural data with smaller sample size than the total sample size due to missing or incomplete data were performed by comparing group characteristics and other pre-intervention primary behavioural measures for the analysed subsample and the total sample using a one-way ANOVA. Differences were considered significant at P<0.05 for the group characteristics and the attrition analyses.All analyses were performed by using SPSS version 19.0. Differences in group characteristics were analysed with a one-way ANOVA or a chi-squared test , post-intervention (T2) and 1-year follow-up (T3)) as within-particpant factor. The full factorial models were tested. All behavioural effects were evaluated using multivariate test criteria. The adjusted difference and 99% confidence interval (99% CI), for the total sample (NFB+TAU and TAU) are reported.Complete case analysis was performed for participants who finished all assessments up to 1 year after the intervention , to determine whether neurofeedback had additional value after completion of the training. The effect of neurofeedback training was investigated using a generalised linear model (GLM) with between- and within-participant factors. To control for multiple tests, effects were considered significant at post hoc analyses were performed to look for three-way interactions involving diagnostic group (ADHD or ASD with comorbid ADHD) or stimulant medication use (stimulant-medicated and stimulant-free) at 1-year follow-up as an additional between-participant factor.To determine whether changes over time were associated with either the co-occurrence of ASD or stimulant medication use, n=27) after randomisation. Separate analyses were performed with ITT analyses based on imputation with last observation carried forward (LOCF) and ITT analyses based on imputation with expectation maximisation (EM). All analyses were performed for the total group as randomised with the exception of the three excluded participants  analyses were performed to control for potential outcome bias of individuals who withdrew (There were no baseline differences for the participants who completed the study up to 1 year post-treatment in group characteristics between the NFB+TAU group and the TAU group . There wn=29), a slight increase in dose was observed from pre-intervention  to 1-year follow-up =4.28, P=0.048, ηp2=0.14). There were no significant interactions between time and treatment group for dosage, F=1.92, P=0.177, ηp2=0.07. In addition, those who used medication at 1-year follow-up (n=30) started stimulant medication at 33 months  before 1-year follow-up with no differences between treatment groups, F=0.73, P=0.400.There were no significant differences between the treatment groups in terms of stimulant medication use at pre-intervention or 1-year follow-up. One participant used atomoxetine and stayed on a stable dose of 60 mg throughout the study. For those who used immediate or sustained release methylphenidate at 1-year follow-up (n=27) did not differ from the completers group (n=60) in terms of group characteristics or behavioural measures at pre-intervention. In addition, the subsamples for the D2 Attention and Concentration Test (n=58) and the Stroop test (n=57) did not differ from the completers sample (n=60) in terms of group characteristics, or behavioural and neurocognitive measures at pre-intervention.Attrition analysis showed that the participants who dropped out for motivational or organisational reasons , irrespective of treatment group (NFB+TAU or TAU). The trend (0.01<P<0.05) found in the complete case analysis for the YSR attention problems subscale  compared with computerised attention training (n=23), 6 months post-treatment in stimulant-free children with ADHD.17 In this study, children for whom stimulant medication was indicated were excluded from the trial or excluded from the follow-up analysis, potentially excluding children with more severe ADHD symptoms. Consequently, the effectiveness of neurofeedback as a treatment for ADHD in this study cannot be generalised to children with more severe ADHD symptoms. A recent published RCT18 did overcome this generalisation problem by including children while standard community care continued, including stimulant medication use by 47% of the participants. They found a larger decrease of ADHD problems from pre-intervention to 6-month follow-up for children that received neurofeedback in addition to standard community care (n=34) than children receiving only standard community care (n=36).18 However, significant results were only found on parent reports, which may be biased in this unmasked study. A meta-analysis into the effectiveness of non-pharmacological interventions15 indeed showed that direct behavioural effects of neurofeedback reduced to non-significant when only probable masked outcomes were considered. In addition, results of a systematic review44 do not support the effectiveness of neurofeedback to enhance neurocognitive functioning.In contrast to the current study, one RCT study found long-term positive results for neurofeedback  using neurofeedback would probably be less pronounced in adolescents with ASD+ADHD than in adolescents with only ADHD. However, in the current study improvements in cognition and behaviour were similar for both diagnostic groups. Similarly, although stimulant-medicated adolescents with ADHD generally display less theta activity than stimulant-free adolescents with ADHD,49 in the current study, use of stimulant medication did not result in different EEG patterns45 or intervention outcomes. The absence of specific effects between stimulant-medicated and stimulant-free adolescents might be explained by the fact that the majority of the stimulant-medicated adolescents used stimulant medication for 6 months or longer at study entry,43 instead of only acute medication effects that are frequently reported in the literature.The effects of comorbid ASD and stimulant medication use and possible interactions with the effects of the treatment over time were also explored in the current study. Adolescents with comorbid ASD did not respond to the interventions differently from adolescents with ADHD only. Analysis of EEG activity at pre-intervention revealed that during resting with eyes open and during task performance adolescents with combined ASD+ADHD showed significant less theta activity than adolescents with only ADHD.post hoc analyses for the presence of comorbid ASD and stimulant medication use. It should however be noted that splitting up the treatment groups for these aspects leads to analyses of relatively small subgroups and a subsequent decrease in power for the analyses. Accordingly, conclusions with regard to ASD and stimulant medication should be interpreted cautiously. Further research, comparing neurofeedback with stimulant medication, titrated with a stepwise double-masked placebo-controlled protocol is essential to see whether neurofeedback is able to be a long-term alternative for stimulant medication. Another point of consideration is the absence of masking of the current study. Masking ensures that expectations about the treatment do not create a bias in favour of one of the randomised treatment conditions. However, in the current study, no additional value of neurofeedback was found. Therefore, it seems unlikely that a positive expectation bias has influenced the results. Another limitation is the low response rate for the parent reports at follow-up, which could therefore not be statistically evaluated. Most studies into the effectiveness of neurofeedback included parent reports, sometimes combined with teacher reports on behaviour. Accordingly, the absence of parent reports and use of self-reports decrease the ability to directly compare the current study to former studies. On the other hand, the use of self-reported behavioural data give new information about whether or not participants themselves notice improvements in behaviour over time.By investigating the long-term effects of neurofeedback as an additional treatment for adolescents with ADHD with a combination of behavioural and neurocognitive measures, we aimed to ensure the ecological validity of the current study. Nevertheless, this also resulted in several limitations. For example, the target population consists of a heterogeneous group of male adolescents with complex problems in a broad age range, and there was variety in the prescription of stimulant medication. To explore possible interactions within this heterogeneous population, we performed 50 and the requirement for intensive training (20–40 sessions),10 the use of theta/SMR neurofeedback as a treatment for adolescents with ADHD is not supported.In conclusion, 1 year after treatment the reduction in ADHD symptoms and improvements in neurocognitive performance were similar in adolescents who received neurofeedback in addition to TAU and adolescents receiving TAU alone. These results do not support the use of theta/SMR neurofeedback as complementary treatment for TAU to produce enduring improvements in behaviour or neurocognitive functioning in adolescents with ADHD. Considering the absence of robust additional long-term effects of neurofeedback, combined with the absence of specific effects of neurofeedback over sham neurofeedback


Mesenchymal stem cells (MSCs) are widely investigated in clinical researches to treat various diseases. Classic culture medium for MSCs, even for clinical use, contains fetal bovine serum. The serum-containing medium (SCM) seems a major obstacle for MSCs-related therapies due to the risk of contamination of infectious pathogens. Some studies showed that MSCs could be expanded in serum free medium (SFM); however, whether SFM would change the biological characteristics and safety issues of MSCs has not been well answered.Human umbilical cord mesenchymal stem cells (hUC-MSCs) were cultured in a chemical defined serum free medium. Growth, multipotency, surface antigen expression, telomerase, immunosuppressive ability, gene expression profile and genomic stability of hUC-MSCs cultured in SFM and SCM were analyzed and compared side by side.in vitro culture.hUC-MSCs propagated more slowly and senesce ultimately in SFM. SFM-expanded hUC-MSCs were different from SCM-expanded hUC-MSCs in growth rate, telomerase, gene expression profile. However, SFM-expanded hUC-MSCs maintained multipotency and the profile of surface antigen which were used to define human MSCs. Both SFM- and SCM-expanded hUC-MSCs gained copy number variation (CNV) in long-term hUC-MCSs could be expanded in SFM safely to obtain enough cells for clinical application, meeting the basic criteria for human mesenchymal stem cells. hUC-MSCs cultured in SFM were distinct from hUC-MSCs cultured in SCM, yet they remained therapeutic potentials for future regenerative medicine.The online version of this article (doi:10.1186/scrt522) contains supplementary material, which is available to authorized users. Total RNA was extracted and then qualified by formaldehyde agarose gel electrophoresis. After being quantitated spectrophotometrically, 1 μg total RNA was used to synthesize double-stranded cDNA and then produced biotin-tagged cRNA using the MessageAmp™ II aRNA Amplification Kit (Invitrogen). According to the protocol from Affymetrix , bio-tagged cRNA was fragmented and hybridized to Human Genome U133 Plus 2.0 containing over 47,000 transcripts. After hybridizing, the arrays were washed, stained by Affymetrix Fluidics Station 450 and scanned by GeneChip Scanner 3000. The intensity values of different microarray were normalized and logMAPK8 and PIK3R1. MAPK8 and PIK3R1 were selected because they implicated in a large number of pathways. GoTaq Green Master Mix  was used for real-time PCR in the 7300 real-time PCR System (Applied Biosystems). Relative expression levels were calculated using ΔΔCT method. Seven housekeeping genes were selected as the candidates of reference genes, and we used geNorm [Real-time PCR was used to validate the data obtained from the mRNA microarray. Twelve differentially expressed genes including six upregulated genes and six downregulated genes were selected for validation by real-time PCR. These 12 genes included genes related to the cell cycle pathway, histone, cytokine, d geNorm  for chooin vitro. Compared with hUC-MSCs expanded in SCM, the population-doubling time of hUC-MSCs cultured in SFM was prolonged significantly, which meant hUC-MSCs proliferated more slowly in SFM. The population-doubling time of SCM-cultured hUC-MSCs was maintained relatively constant, which was shorter than 2 days before the 20th passage  at the 10th passage, propagated in SFM and SCM, were assessed by aCGH. Both of the samples showed CNV during s Figure a,b,c,d. 2 ratio of CNV segments observed in this study averaged 0.31, indicating that only a small subpopulation of hUC-MSCs contained these alterations. In other words, hUC-MSCs, at least cultured hUC-MSCs, were a heterogeneous population in the genome.The loss in chr3:181315609 to 181344028, which was found in both of the SFM-derived hUC-MSCs, did not appear in either of the SCM-expanded hUC-MSCs  genes were in the list of downregulated genes. Considering that cyclin and CDK play the role of key regulator in the cell cycle [cyclin and CDK might explain why hUC-MSCs proliferated more slowly in SFM. Besides, we also found that almost all genes in Mini-Chromosome Maintenance (MCM) complex were downregulated in SFM. MCM, as a key component of the prereplication complex, is very important for the initiation and elongation of DNA replication [MCM might suppress the synthesis of DNA and then slow the proliferation of hUC-MSCs in SFM. Furthermore, genes encoding growth factor and their receptor, such as EGF and EGFR, VEGF and VEGFR, were also downregulated in hUC-MSCs cultured in SFM. Accordingly, a decrease in growth factor and growth factor response might also suppress the growth rate of hUC-MSCs in SFM [We found that 34 genes in the cell cycle pathway were downregulated Figure  in SFM cll cycle , the dowlication , 37. Dows in SFM .Figure 5RFC3, RFC4, RFC5, EXO1, POLE2) involved in the mismatch repair and nucleotide excision repair pathway were downregulated in SFM-expanded hUC-MSCs. There are two possible reasons that could explain this phenomenon: instability of genome and reduced growth rate. The aCGH data did not support a striking increase of CNV in SFM-expanded hUC-MSCs, so we cannot blame genome instability for the downregulation of DNA repair-related genes. Reduced growth might thus be a more reasonable explanation. A reduced growth rate led to fewer DNA replications and less DNA errors. So the requirements for mismatch repair and nucleotide excision repair were reduced in SFM-expanded hUC-MSCs. Interestingly, we observed at least five histone-related genes upregulated in SFM-expanded hUC-MSCs: HIST1H2AC, HIST1H2BC, HIST1H2BD, HIST1H2BK, HIST1H4H. However, we have no idea why histone increased their expression level in SFM-expanded hUC-MSCs, and thus this needs to be further studied.Our data also revealed that some genes  were downregulated, while HIST1H2AC and HIST1H2BC were upregulated in SFM-expanded hUC-MSCs.To confirm and strengthen the findings derived from the mRNA chip, we selected 12 genes and measured their expression level by real-time PCR. As shown in Figure ex vivo expansion of MSCs. Only in one out of three commercial SFMs provided by different companies in this study can hUC-MSCs attach and propagate well on the plasma-treated surface. Being similar to the bone marrow-derived MSCs cultured in autologous serum [GPNMB, CXCL12, COL21A1, ITGBL1). However, we found that hUC-MSCs cultured in SFM could be detached much easier in collagenase compared with trypsin.Attaching and proliferating on plastic is a well-described property of MSCs. Fetal bovine serum provides abundant attachment and growth factors that are essential for MSC maintenance and growth. Some SFMs for MSCs are not free of animal-derived components. They need the flask surface to be coated with substrates isolated from animal or human. These substrates are ill-defined and vary significantly between different batches. When compared with animal-derived materials, xeno-free coating substrates that contain components derived from human might be contaminated by communicable pathogens and thus might be more dangerous. While a previous study reported that MSCs may proliferate in three-dimensional cultures without serum and coating substance , the thrus serum , hUC-MSC7[10 hUC-MSCs at the seventh passage in SFM, which met the quantity requirement of MSCs for clinical applications.Here, we build a system with a xeno-free, serum-free, chemically defined medium and a chemically treated culture surface to expand hUC-MSCs. Neither animal-derived or human-derived protein, nor ill-defined component is included in our culture system. This is a stable, safe, controllable system and thus is suitable for preparing hUC-MSCs for clinical application. The growth rate of hUC-MSCs in this system was lower than in SCM, but all hUC-MSCs in this study could propagate for at least seven passages, which means the amount of hUC-MSCs could be amplified more than 2,000 times (about 11 population doublings) before reaching the senescent stage. If the cell number of the primary culture was 1 × 107, we coulin vitro culture. Sometimes, the difference of lifespan between samples was very striking. In the present study, sample 2 maintained proliferative capacities even after 20 passages in SFM. However, sample 4 reached senescence at the 10th passage in SFM. So, we cannot analyze or evaluate SFM for MSCs only in one sample. For fair reproducibility, SFM should be evaluated in MSCs derived from different donors and different tissues.hUC-MSCs derived from different donors showed a different lifespan in in vitro culture. We found that hUC-MSCs gain copy number changes in culture, no matter whether in SFM or in SCM. This was consistent with the finding in adipose tissue-derived MSCs [Considering the close link between genome instability and tumor genesis, whether SFM-expanded MSCs maintain genome stability is also an important safety issue for clinical application. We utilized high-throughput aCGH to evaluate the effect of long-term culture in SFM and in SCM on genomic stability of hUC-MSCs in ved MSCs , but difved MSCs , which mTumorigenicity is a most important safety issue when cellular therapies are applied in clinical trials. Many conventional and new technologies provide abundant methods to analyze the genome stability and tumorigenicity. However, Prockop and Keating suggest that ‘the most reliable and simplest test is: do the cells senesce in culture? If they do, they are unlikely to produce tumors or malignancies in patients’ . PreviouhTERT in SCM-expanded hUC-MSCs, which cannot be found in SFM-expanded hUC-MSCs. Nevertheless, based on the analysis of cell surface marker and multipotency, SFM-expanded hUC-MSCs met the minimal criteria for human MSCs [SFM-expanded hUC-MSCs showed a clear different gene expression profile compared with hUC-MSCs cultured in SCM based on our microarray data. Cell cycle, mitosis and cell proliferation were downregulated in SFM-expanded hUC-MSCs. We observed a low level of man MSCs . The co-man MSCs , 20. TheWe studied biological characteristics and therapeutic potential of hUC-MSCs that were expanded in a serum-free and chemically defined culture. Our results indicated that many growth rate-related biological characteristics of hUC-MSCs were altered in SFM. However, SFM-expanded hUC-MSCs met the basic criteria for human MSCs and also maintained immunosuppressive ability. Besides, SFM expansion did not change the genetic stability of hUC-MSCs. SFM-expanded hUC-MSCs are therefore suitable for clinical application.hTERT and RPLP0 mRNA in SFM-expanded hUC-MSCs and HeLa (positive control) by TaqMan based real-time PCR. No expression of hTERT was detected in SFM-expanded hUC-MSCs derived from five different donors. HeLa were hTERT-positive. (JPEG 352 KB)Additional file 1: Figure S1: Showing quantification of


Adolescents with attention-deficit/hyperactivity disorder (ADHD) are known to be at significantly greater risk for the development of substance use disorders (SUD) compared to peers. Impulsivity, which could lead to higher levels of drug use, is a known symptom of ADHD and likely accounts, in part, for this relationship. Other factors, such as a biologically increased susceptibility to substance dependence (addiction), may also play a role.abuse and substance dependence in adulthood.This report further examines the relationships between childhood ADHD, adolescent- onset SUD, and substance Individuals with childhood ADHD and non-ADHD controls from the same population-based birth cohort were invited to participate in a prospective outcome study. Participants completed a structured neuropsychiatric interview with modules for SUD and a psychosocial questionnaire. Information on adolescent SUD was obtained retrospectively, in a previous study, from medical and school records. Associations were summarized using odds ratios (OR) and 95% CIs estimated from logistic regression models adjusted for age and gender.A total of 232 ADHD cases and 335 non-ADHD controls participated . ADHD cases were more likely than controls to have a SUD diagnosed in adolescence and were more likely to have alcohol  and drug  dependence in adulthood. The subgroup of participating ADHD cases who did not have SUD during adolescence were no more likely than controls to develop new onset alcohol dependence as adults, although they were significantly more likely to develop new onset drug dependence.drug dependence, a disorder associated with neurological changes in the brain. The relationship between ADHD and alcohol dependence appears to be more complex.Our study found preliminary evidence that adults with childhood ADHD are more susceptible than peers to developing  Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) had defined two types of SUDs: substance abuse (substance use that interferes with daily functioning or is associated with recurrent problems) and substance dependence (manifested by an intense desire for the drug of choice and loss of control over use). abuse and substance dependence are grouped together as “substance use disorders”, they are clearly different: substance dependence involves a distinct pattern of neurological changes caused by repeated exposure to a psychoactive substance, while substance abuse does not.Individuals with attention-deficit/hyperactivity disorder (ADHD) are known to be at significantly greater risk for the development of substance use disorders (SUD) compared to their non-ADHD peers. Human brain development occurs in an orderly, rostral-caudal progression. Notably, the nucleus accumbens, sometimes referred to as the “reward center,” is mature by mid-adolescence, while the maturation of the pre-frontal cortex continues until the mid-20′s. Previously, we reported on the association between ADHD and SUD prior to 18 years of age among research-identified childhood ADHD cases and controls from a population-based birth cohort. abuse and substance dependence among individuals with ADHD. This distinction, however, may help to elucidate the complex relationship between the two disorders. This report examines the relationships between ADHD, substance abuse, and substance dependence among adults with research-identified childhood ADHD versus controls in order to explore whether individuals with ADHD are more susceptible to developing the neurological disorder of substance dependence in adulthood, after the typical period of heightened vulnerability in adolescence.The mechanisms underlying the relationship between ADHD and SUD are not fully understood, and previous research has not distinguished between substance Rochester, Minnesota is geographically isolated in southeastern Minnesota and virtually all medical care for residents of Rochester is provided by Mayo Clinic, Olmsted Medical Center, and their 3 affiliated hospitals. The resources of the Rochester Epidemiology Project (REP) provide infrastructure for population-based research. This study employed a birth cohort consisting of all children born between January 1, 1976, and December 31, 1982, to mothers residing in the townships comprising Minnesota Independent School District 535, who continued to live in Rochester until at least age 5 years (N = 5718). Nineteen subjects with severe intellectual disability were subsequently excluded.Our approach to identify ADHD incidence cases consisted of several steps, used multiple sources of information, and relied on recorded history of symptoms, individual test results , and treatment documented in medical and school records that were available for all members of the birth cohort. Details of this process were previously reported. not fulfilled research criteria for childhood ADHD.Identification of ADHD incident cases consisted of applying research criteria to these 1961 children. Subjects were defined as research-identified ADHD incident cases if their school/medical records included various combinations of three different categories of information: 1) met DSM-IV criteria for ADHD, 2) positive ADHD questionnaire results, 3) clinical diagnosis of ADHD. A total of 379 childhood ADHD incident cases were identified. Research diagnostic criteria were met at a mean age of 10.4 years. Non-ADHD controls were identified from the remaining members of the birth cohort who were in the community after 5 years of age, and who had Details regarding the identification of co-occurring psychiatric disorders in childhood among ADHD cases and controls in this birth cohort are described elsewhere, Information about alcohol and/or drug abuse was available in school records  and/or medical records . The school and medical records of each of the ADHD case and control subjects were reviewed by trained abstractors using a detailed protocol, for documentation of a clinical diagnosis of SUD. Additionally, the computerized Medical Diagnostic Index was also searched for any diagnosis related to or including “substance use disorder” among the 379 childhood ADHD cases under study and their matched controls. Adolescent onset “substance use disorder” required documentation of SUD in the medical and or school records prior to 18 years of age. Medical and school records for every member of the birth cohort were reviewed and all documentation about treatment with stimulant medications was abstracted. We have previously described stimulant treatment among this cohort of ADHD cases, including age of onset, dosage, and duration of treatment throughout childhood. Of the 379 subjects with research-identified childhood ADHD identified in our retrospective study, 362 provided continued permission to access their medical records for research and were invited to participate in the adult outcome study. To ensure enrollment of sufficient non-ADHD controls, a random sample of 801 adults from the same birth cohort was also invited to participate. Five control subjects in the prospective study stated they had received a diagnosis of childhood ADHD. We reviewed records from these 5 subjects and determined that they had fulfilled our research criteria for childhood ADHD, but had not been thus classified previously because they had moved from the community before receiving this diagnosis or because of the timing of the original data abstraction. These 5 subjects were therefore reclassified as childhood ADHD cases for all analyses presented in this paper.All participants in the prospective study were administered the Mini International Neuropsychiatric Interview (M.I.N.I), including the module for Adult ADHD. current alcohol dependence or current alcohol abuse. For the purposes of this study, subjects who reported consuming 3 alcoholic drinks within a 3 hour period on 3 or more occasions, but who did not meet criteria for alcohol abuse or dependence, were defined as having heavy alcohol use. Alcohol abuse and alcohol dependence were defined as per the M.I.N.I. Because the M.I.N.I does not ask about lower levels of alcohol use, subjects who did not report “heavy drinking” were defined as no heavy alcohol use. The M.I.N.I. also includes modules for “Non-Alcohol Psychoactive Substance Use Disorders.” The latter modules are completed for each psychoactive substance used in the past 12 months to “get high, to feel better, or to change your mood.” According to the M.I.N.I. administration protocol, a diagnosis of “dependence” pre-empts a diagnosis of “abuse” for all substances. For the purposes of this study, we defined any illicit substance use that did not meet criteria for drug abuse or dependence as drug use without a disorder. Drug abuse and drug dependence were defined as per the M.I.N.I., and drug exposure was defined as drug use, drug abuse, or drug dependence.The M.I.N.I. includes modules on “Alcohol Abuse and Dependence”. Each subject was first asked, “In the past 12 months, have you had 3 or more alcoholic drinks within a 3 hour period on 3 or more occasions?” All subjects responding “yes” to this first item were then asked a series of questions to determine classification as All subjects completed an extensive psychosocial questionnaire that included specific questions about having participated in a treatment program for “alcohol or drinking problems”, “marijuana use,” or “other street drugs or hard drugs.”Characteristics were compared between participating and non-participating ADHD cases and between participating ADHD cases and participating non-ADHD controls using the two-sample t-test for age, the Fisher’s exact test for race, and the chi-square test for all other categorical variables. Current SUD outcomes in young adulthood (as determined from the M.I.N.I.) were first compared overall between individuals with childhood ADHD and non-ADHD controls and then separately stratified by adolescent onset SUD. The association between the 4-level current drug exposure status  and ADHD case status was assessed based on fitting a generalized logits model. The association between current drug dependence and ADHD case status was assessed based on fitting a binary logistic regression model. All logistic regression models included gender and age at participation and all reported odds ratios (OR) are reported as ORs adjusted for age and gender unless otherwise noted. The same approach was used to analyze current alcohol exposure. The Sobel test was used to test whether the estimate of mediation for co-occurring childhood psychiatric diagnoses was statistically significant. Participating adults with childhood ADHD (n = 232) were similar to non-participants (n = 152) in regard to gender, age, ethnicity, rates of co-occurring mental health disorders, and stimulant treatment history. Control subjects were slightly older at the time of follow-up participation, more likely to be female, and significantly less likely to have had a co-occurring mental health disorder during childhood as compared to ADHD cases .ADHD cases were significantly more likely to have SUD diagnosed during adolescence compared to controls  were higher in adulthood among ADHD cases compared with controls  compared to controls . Simply put, as ADHD cases grew into adults, they were both more likely to use drugs and more likely to develop new onset drug dependence than controls. The effect is mediated through co-occurring childhood psychiatric diagnoses, which accounts for 39.2% of the association (p = 0.014).Among the subgroup of participants who did have adolescent onset SUD, rates of drug exposure in adulthood tended to be higher in ADHD cases as compared to controls   while there were no differences in the rates of alcohol abuse  or dependence .Among the subgroup of individuals with adolescent-onset SUD, those with ADHD were significantly more likely to have alcohol dependence  as adults compared to controls  vs. 15.6% (3/19); adjusted OR 3.84, 95% CI 0.95–15.57, p = 0.06). Few participants had received treatment for marijuana or another drug disorder, and we did not find statistically significant effects for other substances.We calculated the rates of substance dependence among ADHD cases and controls who had received any form of treatment for a SUD to examine whether ADHD moderated SUD treatment effects. Overall, we found that individuals with ADHD were more likely than controls to have received treatment for alcohol, marijuana, or other drug use disorders . Forty-seven ADHD cases and 19 controls reported treatment for alcohol disorders. Among study participants who received treatment for an alcohol disorder, ADHD cases were more likely to have alcohol drug dependence, a disorder associated with neurological changes in the brain, in adulthood. This finding suggests that early onset drug use, a factor known to increase the risk of developing substance dependence, does not fully account for the relationship between ADHD and SUD. Overall, the rate of drug exposure (i.e. drug use or drug abuse or drug dependence) was higher in adults with ADHD, suggesting that impulsivity and poor decision-making continue to play a role. However, among individuals who reported any drug use as adults, rates of new onset drug dependence was significantly higher among ADHD cases – suggesting that the relationship is multi-factorial and not fully explained simply by a greater propensity to use drugs. Furthermore, our findings suggest that individuals with ADHD are more likely than their non-ADHD peers to have persistence of substance dependence in young adulthood. Our data did not allow us to evaluate the relationship between individual drugs and adult onset substance dependence because of small cell sizes, and it is possible that results vary depending on substance. We note that marijuana was the most frequently used drug by adult participants in this study. It is important to note that “medical” marijuana was not recommended during the years when members of this birth cohort were children or adolescents, so these findings cannot be attributed to clinician recommendations. Most importantly, while some advocates for “medical” marijuana have suggested marijuana as a potential therapy for ADHD, our findings of heightened susceptibility to adult onset substance dependence give reason for pause.Our study provides initial evidence that individuals with childhood ADHD remain more susceptible than peers (without ADHD) to developing new onset The pre-frontal cortex is an area of the brain that has been implicated in ADHD, alcohol dependence in adulthood. However, ADHD cases that did not develop a SUD in their teens were less likely than peers to drink heavily and they were not at increased risk for developing new onset alcohol dependence.Our findings regarding alcohol use were different. Individuals with childhood ADHD and adolescent SUD were more likely to have While all substances of abuse have action in the brain’s “reward center,” alcohol’s mechanism of action is distinct. Unlike marijuana and most other illicit substances, alcohol freely crosses cell membranes and exerts its actions on a variety of targets, rather than via a specific receptor. Alcohol dependence is highly heritable, with some individuals particularly prone to developing alcohol use disorders and others relatively resistant. For example, specific alleles for genes that encode alcohol dehydrogenase appear to be protective against alcoholism. Animal studies have found that the neuronal sensitivity to alcohol induced excitation is lower in mice that are bred to be “heavy drinkers.” less likely to drink heavily which may be protective from developing alcohol use disorders in both adolescence and adulthood. We cannot tell from our data whether this “liability” is inborn or present early in life, or the result of refraining from substance use during adolescence. Whatever the mediators, they seem to be specifically related to alcohol regulation and do not protect individuals from developing drug dependence as adults. While the causes remain unclear, it seems prudent to counsel adolescents with ADHD to avoid alcohol use. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has recommended alcohol screening and brief intervention for children as young as 9 years old, the age prior to initiation of alcohol use for most individuals. We speculate that individuals with ADHD can be divided into two groups regarding liability for developing alcohol dependence. Individuals with a “high liability” develop alcohol use disorders in adolescence and have persistent alcohol dependence in adulthood. In other words, adolescents with ADHD may be less likely to “outgrow” an alcohol use disorder than their peers. As in reports from other authors, we found that treatment for SUD is less effective in this group. greater risk for adult drug or alcohol dependence than subjects who only received stimulant treatment prior to age 13 years. Given our finding of increased risk for SUD developing after adolescence among ADHD cases, it should not be surprising that stimulant treatment ending in mid-adolescence would be unlikely to continue to protect against the subsequent development of drug or alcohol dependence. Furthermore, although it cannot be determined from our dataset, subjects who continued to receive treatment after age 13 years may have had more severe ADHD symptoms and hence may have been at greater risk for development of SUD. Future studies that ensure continued stimulant treatment of ADHD through young adulthood may offer an opportunity to better understand the potential impact of stimulant treatment on risk for SUD into adulthood.In our previous retrospective study of the association between stimulant treatment and risk for SUD through adolescence in this cohort of childhood ADHD cases, we found that among boys who were treated, 21.8% had substance abuse compared to 36.4% for those not treated. abuse and substance dependence during adolescence nor to determine which substances were used during adolescence. Our control group was well matched on demographic measures, though co-occurring mental health disorders were more common in ADHD cases than controls, and these disorders play a role in the relationship between ADHD and SUD. It is also possible that other, unmeasured factors may confound our findings. Although our initial cohort of ADHD cases was large, the number of subjects with adolescent-onset SUD followed into adulthood was smaller, contributing to relatively large confidence intervals around estimates of rates of adult SUD in this sub-group; hence, these specific results should be interpreted with caution.Our study has a number of strengths. Our data came from a large, population-based birth cohort and did not depend on a sample referred for ADHD treatment, which typically over represents individuals with the most challenging disorders. Our birth cohort was large, retrospective data was extensive, and our prospective data included a comprehensive, structured neuropsychiatric interview, making our data set unique among published studies of ADHD outcomes. We also note a number of limitations. Our retrospective data did not include age of initiation of substance use, which was not routinely noted in the medical record. Thus, we were unable to evaluate the relationship between age of initiation of substance use and outcomes. Retrospective data were not sufficiently detailed to distinguish between substance This report is the first to utilize a population-based birth-cohort to examine the relationship between childhood ADHD and SUD during young adulthood and to describe differential rates of new onset substance dependence in adults with a history of childhood ADHD. Our findings make an important contribution in understanding the intersection between these two common disorders. Most importantly, our findings underscore the importance of continuous monitoring, prevention and early intervention for substance use among children, adolescents, and adults with ADHD to prevent the development of substance dependence. Further study is needed to determine the most effective mechanisms for achieving these goals.


Attention-Deficit/Hyperactivity Disorder (ADHD) in adults is one of the predictive and treatable risk factors for delinquency, including intimate partner violence (IPV). Effective treatment of IPV needs to address personal dynamic risk factors, offender typology, and dynamics of the domestic violence. It is unknown whether treatment of ADHD symptoms contributes to a decrease in IPV. The ITAP study aims to investigate the relationship between treatment of ADHD symptoms and IPV in patients in forensic mental health care. Moreover, this study examines the role of comorbid psychopathology, subtype of the offender, and dynamics of the domestic violence.The ITAP study is a longitudinal observational study. Participants are followed one year through various assessments: one before starting treatment (t0), and four during treatment . All participants receive treatment for IPV, ADHD, and comorbid psychopathology, if present. The primary outcome measure is the change in severity of IPV; the primary predictive variable is the change in severity of ADHD symptoms. The secondary outcome measure is the observation of the therapist about change in the offender’s general violent behaviour, within and outside the partner relationship. Data are analysed in a multiple regression model with change in severity of IPV as the dependent variable and change in severity of ADHD symptoms as the primary predictor. Other predictive variables taken into account in the analyses are presence of comorbid psychopathology and personality disorder, subtype of the offender, and dynamics of the domestic violence. In addition, compliance with treatment and content of the treatment are documented.Research on the treatment process of IPV offenders and victims is complicated by many factors. This observational design will not allow inferences about causality but may reveal clinically important factors that contribute to more effective treatment of IPV.NTR3887.The Netherlands National Trial Register (NTR), trial ID  The WHO defines domestic violence as “any behaviour within an intimate relationship that causes physical, sexual or psychological harm”. Studies about domestic violence reported a prevalence of nearly 40% in women who attended general practices ,2. In a The consequences for victims of IPV and children who witness IPV are severe. In a WHO multi-country study on women’s health and domestic violence, women who experienced partner violence reported significantly more emotional distress, suicidal thoughts, and suicidal attempts than non-abused women . In a USExisting explanatory models about IPV can be divided into sociocultural, interpersonal, and intrapersonal theories. Sociocultural theories conceptualise IPV as a result of social structures and culturally determined views on the role of men and women. The best-known model within this theory is the Duluth model . InterpeIn the tradition of the intrapersonal theories, many authors proposed classification of offenders in categories. Holtzworth-Munroe and Stuart ,11 suggeAs a part of the interpersonal theory, Johnson ,17 propoThe high prevalence of IPV and the severe consequences for victims and children stress the need for effective treatment. However, two meta-analyses showed that the overall effectiveness of treatment of partner violence is small ,23. An eCase control studies comparing IPV offenders to controls revealed some characteristics. Offenders were more likely to have witnessed parental DV in their families of origin and were more likely to have been abused as a child ; they haAttention-Deficit/Hyperactivity Disorder (ADHD) is one of the dynamic risk factors for delinquency. Several studies have shown that impulsivity and hyperactivity in childhood specifically predict future delinquency, to a large part, but not only, through the association with conduct disorder  in adults) –34. In pPrevalence of ADHD in children is 5%, and 3% to 4% in adolescents and adults –49. PrevADHD symptoms can be treated effectively in adults. The efficacy of stimulants in reducing ADHD symptoms for adults is well documented in several meta-analyses . Data frThe ITAP study aims to investigate the impact of ADHD and its treatment within a comprehensive treatment approach of IPV. The rationale for this study is the hypothesis that successful treatment of ADHD symptoms, such as inattention, hyperactivity, impulsivity, and emotional instability, will decrease ADHD symptoms and lower the risk for and severity of IPV. In addition, the ITAP study attempts to reveal clinically important factors that contribute to a more effective treatment of IPV.The primary objective of the ITAP study is to examine the correlation between change in ADHD symptoms and change in IPV during a 16-week treatment in forensic mental health care for offenders of IPV who also meet criteria of adult ADHD diagnosis.The secondary objective of the ITAP study is to examine the correlation between change in ADHD symptoms and change in indoor and outdoor aggression during a 16-week treatment in forensic mental health care for offenders of IPV who also meet criteria of ADHD.In addition, the ITAP study attempts to analyse the role of potential other predictors of IPV on treatment outcome, measured at t0, such as: a) severity of ADHD symptoms, b) severity of borderline personality disorder problems, c) severity of antisocial personality disorder problems, d) presence of mood disorder, e) presence of anxiety disorder, f) presence of substance use disorder, g) subtype of the offender according to Holtzworth-Munroe and Stuart , h) dynaParticipants are recruited from all patients (men and women) referred to De Waag Utrecht and De Waag Amersfoort in the period from October 2012 to December 2015. De Waag is a forensic outpatient clinic in the Netherlands . Patients are referred to De Waag by court, the probation service, or the primary health care service because of having committed an offence. All patients receive information about the ITAP study at home before intake. The professional who conducts the intake interview asks patients to participate and to sign informed consent.Given existing evidence of effective treatment of ADHD in adults, it was considered ethically incorrect to conduct a randomised controlled trial with a condition in which ADHD is not treated. Therefore, we chose a longitudinal observational design with the focus on predictors for successful treatment of IPV. All patients with recent IPV are asked to participate in the study upon entry at De Waag. After informed consent, patients are interviewed by a trained clinician to diagnose possible adult ADHD or other axis I pathology and axis II pathology. Subsequently, those who are diagnosed with adult ADHD will be included in the study. Next, participants are followed for a period of one year by way of repeated assessments: one before (t0) and four during treatment . The assessments measure the severity of ADHD symptoms, IPV and indoor and outdoor aggression. All participants receive treatment for IPV, ADHD, and other psychopathology, if present. In addition, compliance with treatment and content of the treatment is monitored.Treatment of all participants is based on the Risk Need Responsivity (RNR) model  and matcOther psychopathology is treated according to evidence-based interventions and guidelines. A psychiatrist provides the drug treatment; a family therapist partner relation therapy, and a psychologist psycho–education and skills training.The ITAP study is performed in accordance with the ethical principles laid down in the 1964 Declaration of Helsinki and subsequent amendments. The study is granted an exemption from requiring ethics approval by the medical ethical committee (Commissie Mensgebonden Onderzoek –CMO- Region Arnhem-Nijmegen).Registration number 2012/222; NL number 41031.091.12.The ITAP study is registered at the Netherlands National Trial Register (NTR), trial ID NTR3887.www.divacenter.eu. The interview allows a structured assessment of the DSM IV criteria for ADHD in adulthood and (retrospectively) in childhood. In addition, the severity of dysfunction due to ADHD symptoms is assessed in five areas: work and education, relationship and family life, social contacts, leisure time, and self-confidence and self-image. Clinical experience with ADHD diagnostics is a prerequisite for adequate use of the interview. Each criterion is scored on the basis of the information obtained from the patient  and the clinical judgement of the clinician. The DIVA 2.0 yields both a categorical outcome (ADHD is present/absent) and a dimensional outcome (the number of criteria and areas of dysfunction scored). In this study, a patient is considered to have an ADHD diagnosis when at least 6/9 criteria for attention deficit and/or hyperactivity-impulsivity in childhood and at least 5/9 criteria of attention deficit and/or hyperactivity-impulsivity in adulthood, and at least 2 areas of dysfunction in childhood and adulthood are present (according to DSM-5 [The structured diagnostic interview for ADHD in adults 2.0 (DIVA 2.0) was first developed in Dutch by J.J.S. Kooij, MD PhD, psychiatrist, and M.H. Francken, MSc, psychologist in 2007 . Since Oto DSM-5 ). No resto DSM-5 , and – aThe Personality Disorder Questionnaire Revised (PDQ R) is a screening instrument for DSM-IV-R personality disorders. Sensitivity is high, specificity is low . The PDQThe Structured Clinical Interview for DSM IV Axis II diagnoses (SCID2)  is a genThe Mini International Neuropsychiatric Interview Plus (MINI plus) is a structured interview for assessing diagnoses on Axis I according to DSM IV. Several studies showed adequate psychometric properties of the MINI plus ,68.The ADHD DSM-IV Rating Scale (ADHD RS)  is a widThis study uses the Dutch version of the ADHD RS for adults. This version contains 23 items. The Dutch version has good internal consistency   and is cThe Conflict Tactics Scales (CTS)  is the mThe Modified Overt Aggression Scale (MOAS) ) is a meFor the purpose of this study, we adapted the MOAS to the subject of partner violence to have a second outcome measurement. We left the aggression against oneself out and we asked about behaviour of indoor and outdoor aggression . Because this version of the MOAS has not been validated for this sample, we ask both the patient and the therapist to fill in the questionnaire separately in order to calculate consistency between self-ratings and therapist-ratings.Holtzworth-Munroe and Stuart ,57 diffeJohnson , (2004) At t0 all participants fill in ADHD RS, CTS2 client version, MOAS client version, and PDQ R. The patient’s partner is asked to fill in the CTS2 partner version. Subsequently, a trained clinician administers three clinical interviews, i.e. SCID2, MINI plus and DIVA 2.0 in order to assess proper diagnoses of Axis I, Axis II, and adult ADHD. In addition, the treating therapist fills in the MOAS therapist version and assesses the subtype of the offender according to Holtzworth-Munroe and Stuart and the dynamics of the domestic violence according to Johnson. Only participants with severe IPV and ADHD diagnosis assessed by DIVA 2.0 see  are inclAt t1 (8 weeks after start of treatment), t2 (16 weeks after start of treatment), t3 (24 weeks after start of treatment), and t4 (52 weeks after start of treatment) all participants fill in the CTS2 client version, the ADHD RS, and the MOAS client version. Partners fill in the CTS2 partner version. Therapists fill in the MOAS therapist version and assess compliance with treatment.There are six inclusion criteria for the ITAP study:The participant must be 18 years of age or older.The participant must be decisionally competent and willing to give informed consent.The participant must have sufficient command of the Dutch language to fill in questionnaires.The participant must have completed the self-report questionnaire on IPV in the period of 8 weeks prior to intake.The severity of the IPV is at least moderate, operationalised by a score of at least 1 on the physical assault subscale of the Conflict Tactics Scale (CTS2), or a score of at least 1 on the injury from assault subscale of the CTS2, or a score of at least 3 on the psychological aggression subscale of the CTS2, or a score of at least 2 on the indoor aggression part of the MOAS.Presence of ADHD diagnosis according to the DSM-5 as established on the basis of a clinical assessment: the DIVA.Patients with acute severe mental symptoms that require immediate crisis interventions will be excluded. This is assessed at the beginning by the professional who conducts the intake interview with the patient and during treatment by the treating therapist.The primary study outcome is the change in severity of IPV between t0 (before starting treatment) and t2 (after 16 weeks of treatment). The change in IPV is calculated by the difference in scores on the CTS2 client version between t0 and t2.The secondary study outcome is the observation of the therapist about any change in indoor and outdoor aggression, determined by the difference in scores on the MOAS therapist version between t0 and t2.The primary predictive variable is the change in ADHD symptoms between t0 and t2, determined by the difference in scores on the ADHD RS between t0 and t2. Compliance with treatment, as determined by the number of treatment sessions received at t2, is a covariate predictor.Severity of ADHD: assessed by the DIVA 2.0; dimensional score;Severity of borderline personality disorder problems, assessed by the SCID2; dimensional score;Severity of antisocial personality disorder problems, assessed by the SCID2; dimensional score;Presence of mood disorder, assessed by the MINI plus; categorical score;Presence of anxiety disorder, assessed by the MINI plus; categorical score;Presence of substance use disorder, assessed by the MINI plus; categorical score;Subtype of the offender by Holtzworth-Munroe and Stuart, assessed by structured clinical assessment by the therapist; categorical score;Dynamics of the domestic violence by Johnson, assessed by structured clinical judgment by the therapist; categorical score.Other covariate predictors, scaled at t0 are:Data will be analysed in a multiple regression analysis with change in IPV as dependent variable and change in ADHD symptoms as primary predictor. Taking alpha = 0.05, two-sided, a sample size of 131 participants at t2 has 80% statistical power to detect a standardised regression-coefficient of 0.25. With this sample size, a beta of 0.25 corresponds to an effect size of 0.5, which is considered a clinically relevant effect. A maximum of 10 predictors is included in this analysis. Given the target sample, a drop-out rate of 25% has to be taken into account. This means that the desired sample size at t0 is 164 participants.First of all, data will be analysed with SPSS in a multiple regression analysis with change in IPV at t2 as dependent variable and change in ADHD symptoms at t2 as primary predictor. Covariate predictors  will be included in the analysis. The primary analysis is with completers. Additionally, an intention to treat analysis will be carried out using the last-observation-carried-forward method.Later on, an additional and exploratory analysis will be carried out in which all time points are examined by using a multilevel-mixed model approach.The high prevalence of IPV and the severe consequences for victims and children stress the importance of focusing on adequate therapy. However, little is known about effective treatment of IPV. The primary objective of the ITAP study is to examine the role of ADHD and its treatment within a comprehensive treatment approach of IPV. The ITAP study attempts to demonstrate the importance of detecting and treating ADHD as one of the dynamic risk factors for IPV. Our primary hypothesis is that ADHD treatment response will lower the risk for IPV. If this hypothesis is confirmed, this insight may contribute to the practice of diagnostics and treatment of IPV offenders. Additionally, the ITAP study examines the presence of comorbid psychopathology and includes this information in the analysis. Hence, results of the ITAP study are also expected to provide more insight into the contribution of comorbid psychopathology and its interaction with ADHD to the extent and severity of IPV. Furthermore, the ITAP study is expected to reveal more information about the importance of determining offender types, dynamics of the relationship and, finally, how this knowledge will influence the treatment of IPV. Although the prevalence of these classifications in IPV has been studied thoroughly, the benefits of these classifications within the treatment of IPV have never been examined. In most studies, offender types were determined by cluster analysis and not by clinical assessment. Little is known about the reliability of these parameters, when classified by clinicians for practical use. The inter-rater reliability is presumably problematic; therefore, data from the ITAP study can also be used for establishing this reliability.Exploring the relationship between ADHD and IPV in a longitudinal design is challenging and research in this field will have to address several practical and methodological obstacles. Firstly, as mentioned above, a randomised controlled trial would provide stronger evidence for causality; however a design in which one group of ADHD patients is not treated is considered unethical. This observational design will not allow inferences about causality, but we hope to detect a strong association between severity of ADHD symptoms and that of IPV. Secondly, relationships of couples with IPV are usually very unstable. This may lead to problems with follow-up assessments, since change in IPV can only be measured if couples have at least regular contact. For this reason we extended the CTS2- and MOAS follow up questionnaires with questions about the actual situation: still living together, not living together anymore but frequently having contact, separated but still having contact, and contact with children, if any. Thirdly, the drop-out rate in forensic psychiatry is generally high and even higher in ADHD patients. Therefore, in estimating the sample size, a drop-out rate of 25% was taken into account. Fourthly, forensic patients tend to have little insight in their behaviour and problems or are inclined to trivialise it. This may result in lower scores on t0 self-reports and make it difficult to detect change. In addition, one of the intended effects of therapy is to improve self-reflection and self-understanding. Treatment with ADHD medication, for instance, often provides more insight into problematic behaviour. There is a slight possibility that this mechanism results in higher scores on follow up self-reports, such as ADHD RS, CTS2, and MOAS client version. In that case, a feasible decline of symptoms or improvement in behaviour is not properly reflected by the scores on the self-reports. Scores on the MOAS therapist version and the CTS2 partner version can meet these objections for the part of the change in IPV; in the case of a change in ADHD symptoms, it is harder to overcome these objections.In spite of this, the ITAP study will provide more insight into the complex matter of treatment of IPV in clinical practice and may reveal clinically important factors that contribute to more effective treatment of IPV.


ADHD children have anomalous and negative behavior especially in emotionally related fields when compared to other. Evidence indicates that attention has an impact on emotional processing. The present study evaluates the effect of emotional processing on the sustained attention of children with ADHD type C. Sixty participants form two equal groups (each with 30 children) of normal and ADHD children) and each subject met the required selected criterion as either a normal or an ADHD child. Both groups were aged from 6–11-years-old. All pictures were chosen from the International Affective Picture System (IAPS) and presented paired emotional and neutral scenes in the following categories: pleasant-neutral; pleasant-unpleasant; unpleasant-neutral; and neutral–neutral. Sustained attention was evaluated based on the number and duration of total fixation and was compared between the groups with MANOVA analysis. The duration of sustained attention on pleasant in the pleasant-unpleasant pair was significant. Bias in duration of sustained attention on pleasant scenes in pleasant-neutral pairs is significantly different between the groups. Such significant differences might be indicative of ADHD children deficiencies in emotional processing. It seems that the highly deep effect of emotionally unpleasant scenes to gain the focus of ADHD children’s attention is responsible for impulsiveness and abnormal processing of emotional stimuli.  Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychological disorders that initially manifests in childhood with clinical behavioral signs of inattention, hyperactivity, and impulsivity , 2. OfteA total of 60 male participants aged from 6–11-years of age participated in this study. The participants were divided into two groups: normal and ADHD (each with 30 participants). The participants met the required selection criterion for either normal or ADHD children. To estimate the possible normality and abnormality, K-SADS-PL interview (Persian version), the Scale Rating ADHD, and Conner’s Parent Rating Scale Revised tests were completed by the parents of children. The participants were all right-handed and had either 20/20 vision or vision corrected with glasses. Subsequently, the Ishihara test was conducted on the participants to ensure that they did not have any problems in perceiving colors appropriately on the screen. It is worth mentioning that none of the participants in either group had previously attended any psychological or rehabilitation centers. They did not have any previous experience in working with eye-tracking devices or other supplementary treatment like neuro-feedback. Images of scene The images (sized as 397 x 429) used in this study were chosen from the International Affective Picture System (IAPS). These pictures are selected to correspond to the age of the children who were participating in this study. The pictures were categorized as “neutral”, “pleasant”, or “unpleasant” based on the content and the scale of their valence with a valence from 4.5–6 as neutral, a valence below 4.5 as unpleasant, and the valence above 6 as pleasant . The picThe acceptable conditions for fixation were as follows: Those within the area of interest (both pictures were predetermined by the researcher as areas of interest) (Interest of Area: IOA). Those that were recorded for at least 100 msec after the presentation of the pictures had started. Those for which the minimum and maximum recorded duration were 100 and 2500 msec, respectively. And, those that did not continue for more than 50 msec after the presentation had ended. All test procedures were conducted in stress free conditions. The participants sat in armchairs in a dimly lit room while there was a desk in front of them on which a monitor with a chin rest, an adjustable height, and other side adjustments (like face fixer in front of the monitor screen) was placed to keep the distance from the monitor unchanged and fixed at 57 cm during the trials. The participants were asked to look at the paired pictures of their own will. Before the pictures were presented, calibration and validation were done. At the drift correction stage, the participant was asked to gaze at a black spot at the center of the screen. Additionally, the drift correction at the beginning of the presentation for each trial was done manually. Each trial stayed on the screen for 3000 msec after which the black spot reappeared. This process continued until all pictures were presented once (N=116) and was restarted after a 15-minute break to avoid the participants feeling tired. The results indicate that there is no significant difference in duration of sustained attention  = 1.55, P = 0.17). Nor is there any significant difference between the two groups as far as the total number of fixations was concerned  = 1.49, p = 0.19). Also, Table shows that ADHD children focus on pleasant pictures in pairs of pleasant-unpleasant less than normal children did  = 1.89, p = 0.18). Estimation of Bias Attentional bias was also estimated in relation to (a) the number of total fixations (ABNTF), and (b) duration of sustained attention (ABDSF). These indices were estimated on each category of the picture pairs. Attentional bias in total number of fixations (ABNTF) was calculated as follows:The value of ABNTF should be greater than 0.5 to indicate a groups’ bias in terms of a number indicating the emotional picture in any pair . Table 2The second type of bias estimation in this study was achieved through an estimation of the duration of sustained attention (ABDSF) through the following operationThe value of ABDSF should be positive to indicate bias towards emotional patterns in any selected pair . Table 3The results indicated that there was no significant difference in attentional bias between two groups as far as duration of sustained attention is concerned. Wilks’ Lambda indicated it was insignificant  = 2.10, P = NS). However, both groups were significantly different in terms of total number of fixation, F  = 2.77, P =0.05. We have attempted to investigate the nature of sustained attentional bias in ADHD children through focusing on number and duration of sustained attention using Eye- Tracking II. The mean differences showed that ADHD children tended to have more and longer sustained attention to unpleasant scenes in different unpleasant-neutral or pleasant pairs, though insignificantly. Even in pleasant-neutral pairs, ADHD children more likely attended to neutral scenes than pleasant ones. This result was consistent with the findings of other studies that ADHD children might suffer from emotional processing problems , 19-21. To some scholars , 23, ADHThe result of attentional bias to emotional images suggested that ADHD children looked at unpleasant pictures significantly longer than pleasant and neutral images. Furthermore, these children apparently focused on unpleasant pictures in both unpleasant-pleasant and unpleasant-neutral pairs, though insignificantly. The interesting point is that ADHD children seemed to have sustained attentional focus on neutral in pleasant-neutral children more than healthy children in non-significant trends have; the p-value is the “Trend” (41). ADHD children had a greater number of fixations on unpleasant pictures in either pairs of unpleasant-pleasant or unpleasant-neutral when compared to healthy children. The results indicated that both groups of children seemed to be attentively biased towards the pleasant pictures in the pleasant-neutral pair; however, ADHD children had significantly less severe reactions than normal children did. This indicated that ADHD children presumably had less severe reactions to pleasant pictures in either the pleasant-unpleasant or pleasant-neutral pairs, whereas they had shown longer sustained attention to unpleasant images in unpleasant-neutral and unpleasant-pleasant pairs. The result of this study can be supported by a hypothesis related to posterior right hemispheric dysfunctions , 27. ThePersons with ADHD experience increased difficulty in scanning and selecting relevant aspects of stimuli. They notice fewer targets, make more perceptual errors, and have reduced reaction times, all factors associated with at least frontostriatal dysfunction. Therefore, persons with ADHD exhibit developmental anomalies in the frontostriatal neural networks associated with varying degrees of attending problems. One of the problems has been the correct perception of FEE . One way of regulating emotion is “Employment of Attention” in selecting specific situations and tolerating the related time-span. In this respect, prior research has shown that ADHD children suffered from abnormal eye movement in facing emotions and, thereby, had problems in regulating and sustaining their attentional focus on images . These iBarkley (1990) indicated that ADHD children had difficulty in sequencing and narrating events. This problem might be related to a deficiency that ADHD children have in receiving visual information through less fixations on emotional scenes. In summary, when pleasant and unpleasant images were presented simultaneously, there was a preferential attention to the latter in ADHD children , 31, 32.In conclusion, the present research reveals that ADHD children’s impulsiveness might be the result of their exceptional focused attention on emotionally unlearned scenes. However, the authors would suggest further research be done to include both male and female children as well as investigating other types of ADHD attentional focus. Moreover, in the present research, we had limited access to the possible number of emotional images appropriate for children.


Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for problematic cannabis use. However, clinical and anecdotal evidence suggest an increasingly popular perception that cannabis is therapeutic for ADHD, including via online resources. Given that the Internet is increasingly utilized as a source of healthcare information and may influence perceptions, we conducted a qualitative analysis of online forum discussions, also referred to as threads, on the effects of cannabis on ADHD to systematically characterize the content patients and caregivers may encounter about ADHD and cannabis.A total of 268 separate forum threads were identified. Twenty percent (20%) were randomly selected, which yielded 55 separate forum threads  scored by three raters (Cohen’s kappa = 0.74). A final sample of 401 posts in these forum threads received at least one endorsement on predetermined topics following qualitative coding procedures.Twenty-five (25%) percent of individual posts indicated that cannabis is therapeutic for ADHD, as opposed to 8% that it is harmful, 5% that it is both therapeutic and harmful, and 2% that it has no effect on ADHD. This pattern was generally consistent when the year of each post was considered. The greater endorsement of therapeutic versus harmful effects of cannabis did not generalize to mood, other (non-ADHD) psychiatric conditions, or overall domains of daily life. Additional themes emerged .Despite that there are no clinical recommendations or systematic research supporting the beneficial effects of cannabis use for ADHD, online discussions indicate that cannabis is considered therapeutic for ADHD—this is the first study to identify such a trend. This type of online information could shape ADHD patient and caregiver perceptions, and influence cannabis use and clinical care. Cannabis use disorder (CUD) refers to a problematic pattern of cannabis use leading to clinically significant impairment or distress within a 12 month period and includes at least two symptoms occurring in this context  . ADHD adindependent of cannabis use, including neurocognitive deficits [This relationship between ADHD and cannabis use is relevant given the known adverse effects of use. For instance, short-term effects of cannabis use include impaired short-term memory and motor coordination, altered judgement, and (in high doses) paranoia and psychosis . Real-wodeficits , 16 and deficits , the maldeficits  and altedeficits , along wdeficits . Furtherdeficits  and suchdeficits .Despite the increased risk for problematic cannabis use outcomes, anecdotal clinical observations suggest there is a growing popular perception that cannabis is therapeutic for ADHD. Even some medical professionals have advocated for cannabis as a treatment for ADHD, including before a congressional subcommittee on drug policy   “marijuana,” cannabis,” “pot,” or “weed,” with (c) “forum.” At least the first 50 results that emerged from each search were considered. Forum threads that included links to any other forum threads addressing ADHD and cannabis were also included. This resulted in a total sample of 268 forum threads identified for the current study.A search via Google, the most frequently used online search engine in the US , was conSD = 17.22, range = 1 to 85, median = 13, mode = 4). A random selection of 20% is consistent with other qualitative studies of online forums on the topic of substance use [SD = 17.97, range = 1 to 85 posts, median = 15, mode = 15). Among the 46 threads, 27 (59%) were hosted on sites devoted to ADHD generally , 10 (22%) were hosted on sites devoted to cannabis generally , 6 (13%) were hosted on sites devoted to overall physical or mental health generally , and 3 (7%) were hosted on other sites .We randomly selected 55 threads (20%) for analysis, which were coded for the presence or absence of particular topics see  below. Tance use  and yielance use , 50. TheA total 479 of the 880 individual posts within the 46 threads did not receive an endorsement for various reasons, such as thanking others for commenting on a question, introducing themselves to the discussion, or tangentially commenting on a discussion about cannabis and ADHD . These posts were excluded given the primary aim of this study to characterize the content of comments on ADHD and cannabis. A total of 401 individual forum posts received at least one topic endorsement within the 46 threads see  below. Sa priori by the authors for anticipated online forum discussions involving cannabis and ADHD based on knowledge of the literature and aims of this study. This was followed by a review of 266 individual posts across 30 different threads, prior to random selection of posts, to assess topics that emerged that were not previously considered in the first stage. The authors then finalized the list of specific topics that were coded based on the primary aims of the current study—additional topics on the subject of ADHD and cannabis were coded as well, but are not reported in this study. All 401 individual posts analyzed in this study received at least one endorsement from any of the topics on the subject of ADHD and cannabis used in the coding process .A list of topics for coding individual posts in a binary response format  was created through an iterative process. First, a list of potential codes was created Among the topics that were coded for the current study, we assessed if cannabis was stated to impact ADHD or ADHD symptoms, mood, non-ADHD psychiatric disorders, and different domains of daily living . For each of these topics, coding was carried out to indicate if the effect of cannabis was stated to be therapeutic, harmful, or both therapeutic and harmful. For the code on the effect of cannabis on ADHD, a null effects option  was also included—null effects were not coded for cannabis effects on mood, non-ADHD psychiatric disorders, or different domains of daily living given that this endorsement option was not observed in the code creation process. Comments about medicinal aspects of cannabis in the context of ADHD were also coded see .The randomly selected 20% of forum threads were all read in full by one of three raters. From these forum threads, 401 individual posts received at least one code endorsement by a rater. In cases where a person posting quoted another post that was endorsed but they themselves did not clearly endorse or provide sufficient information for the rater to determine if an endorsement was warranted for a particular code, then an endorsement was not made by the rater. Multiple posts by the same person (as indicated by a user identification name or number) were allowed since the main purpose of this study was to assess what forum users might be exposed to when looking for information on the topic of ADHD and cannabis use, therefore multiple posts by the same person would not have a meaningful impact on interpretation of the results.A random selection of 10% of posts was coded by the other two raters for inter-rater reliability. The average agreement between each grouping of raters was 93% (range: 92%-93%). Cohen’s kappa takes chance agreement into account and was 0.74 (ranging from 0.72 and 0.76 between different pairs of raters), indicating substantial agreement .Examples that typified endorsements for different topics are reported. Spelling and grammatical errors were not corrected, although vague use of pronouns  were replaced with specific terms used elsewhere in the post  and denoted by use of parentheses. Also, use of “…” within quotes indicates sections that were removed to allow for brevity while maintaining the overall context of the quote.The majority of forums (59%) included posts that advocated for the therapeutic effects of cannabis for ADHD . In terms of comments about cannabis as therapeutic for ADHD or ADHD symptoms, below are examples that typified endorsements for this topic:“Marijuana works for ADHD”"(Cannabis) helps me greatly with my ADHD"“In regard to the ADD, while you are high … you will be able to focus much, much better than you normally would.”“medical marijuana improves the ability to concentrate in some types of ADD.”“There are many, many studies showing the efficacy of  for ADD.”Regarding the relatively fewer posts about cannabis’ adverse effect on ADHD or ADHD symptoms, typical comments included:“For me, pot does nothing for my ADD. If anything, it makes it worse. I cant pay attention sober much less high.”“Smoking weed is bad for people with ADHD.”Cannabis both helps and makes (my ADHD symptoms) more intense” emerged.Among the few that stated cannabis is both therapeutic and worsens ADHD, comments such as “(Cannabis) helps me focus” and “i find im able to concentrate so much better after a bit of cannabis"), 16% (10 posts) that cannabis helped hyperactive-impulsive symptoms  sort of helps eliminate excess pent up hyperactivity” and “i just smoke (cannabis) everyday after school and then around night and im good i dont get to hyper and i have total control of how i act”), and 10% (6 posts) that cannabis helped both inattentive and hyperactive-impulsive symptoms  attend class stoned … (I am) more focused and less nervous and hyperactive” and “(I) use pot for (ADHD), and it helps quell racing thoughts, hyperactivity, and rage, while considerably extending attention span.”).Within the 99 posts that endorsed that cannabis improved ADHD or ADHD symptoms, there were 62 posts that mentioned improvement on at least one DSM-5 ADHD symptom set , as opposed to posts that stated that cannabis helped ADHD but not at the symptom level. Among the 62 posts that commented on ADHD symptoms, 74% (46 posts) endorsed that cannabis helped inattentive symptoms . As shown in I am 21 years of age and strongly believe in medical marijuana and why people with adhd should be getting percribed it in this country” and then listed a link to a website from a physician purportedly advocating cannabis as a treatment for ADHD. Other examples of posts that typified this topic include:Comments about the medicinal aspects of cannabis use in the context of discussing ADHD were also considered across the 401 posts . Overall“(A physician) has also worked with one family of a 15-year-old—whose family had tried every drug available to help their son, who by age 13 had become a problem student diagnosed as suffering from ADHD. Under (a physician’s) supervision, he began marijuana treatment, settling on cannabis in food and candy form, and he has since found equilibrium and regularly attends school.”“I have ADD and I use  for it. It works very well. I'm 64 and was diagnosed with adult ADD 4 years ago. I had it confirmed by two MD's and a psychiatrist.…I now use marijuana exclusively.”This study is the first to systematically analyze a source of online information that patients and caregivers may use to inform their opinions about ADHD and cannabis. A qualitative analysis examining the content of online forum threads on the topic of ADHD and cannabis use indicated that at least three times as many comments advocated for therapeutic effects of cannabis on ADHD compared to comments that cannabis is harmful, both therapeutic and harmful, or has no effect on ADHD. The disproportionate number of comments favoring the therapeutic over harmful effects of cannabis was specific to ADHD and was not generalizable when mood, non-ADHD psychiatric conditions, or general quality of life were considered. Analysis of the temporal distribution of posts about the effects of cannabis on ADHD indicated that the tendency to advocate for its therapeutic effects has generally been consistent since 2006. Qualitative analysis also indicated that comments purporting the therapeutic effects of cannabis for ADHD predominantly referenced improvement in inattentive symptoms, as opposed to hyperactive-impulsive symptoms. Relatively few comments comparing cannabis against ADHD medications emerged. However, there were a number of comments indicating that cannabis is considered “medicinal” or sanctioned by healthcare providers.The primary motivation in conducting this analysis was to systematically identify and analyze a source of information patients and caregivers might access to learn about the effects of cannabis use on ADHD. The majority of US Internet users query the Internet for healthcare information . This neindependent of cannabis use [Our findings indicating bias towards cannabis being beneficial for ADHD is consistent with national trends about the decreased perceived risk associated with regular cannabis use  and is rabis use , 16—emerabis use . ConsequThe current findings demonstrate that an online source that may be used by caregivers and patients with ADHD seeking more information about cannabis favors the beneficial effects of use on ADHD. Future studies are needed to assess if these attitudes are endorsed by ADHD patients. To our knowledge, only one study has examined perceptions of cannabis use in ADHD , though In terms of study limitations, although data was collected from a resource that patients and caregivers may use to learn about cannabis and ADHD , it is unclear how often ADHD patients and caregivers access this online resource or online resources in general to learn more about treatment options. However, past studies do demonstrate that individuals seek out healthcare information online  and thatIn summary, there is a dearth of systematic studies analyzing a source of online information patients and caregivers might access to learn about the effects of cannabis on ADHD—this is the first study, to our knowledge, to do so. Our findings involving the trend of online forum threads advocating for the therapeutic effects of cannabis for ADHD are particularly important since patients and caregivers seek out information online. Moreover, this topic is likely to be increasingly broached in clinical settings. This study also demonstrates the utility of online data to examine trends in substance use and inform future studies. In particular, findings from this study indicate the need to assess perceptions involving cannabis use and ADHD in ADHD patients, in addition to examining the objective effects of cannabis use on ADHD symptoms and associated features.S1 DatasetIn this Excel file, we provide one file: S1_Dataset.xlsx.(XLSX)Click here for additional data file.


Dear Editor,ADHD predicts future substance abuse/dependence . In the