ADHD is the one of the most prevalent childhood disorders and has been associated with impairments persisting into adulthood. Specifically, childhood ADHD is an independent clinical risk factor for the development of later substance use disorders (SUD). Moreover, adults who meet diagnostic criteria for ADHD have shown high rates of comorbid SUDs. Few studies, however, have reported on the relationship between ADHD subtypes and SUD in adult samples. The purpose of this study was to characterize a clinical sample of adults with ADHD and to identify possible associations between ADHD subtypes, lifetime substance use, and if ADHD subtypes may be preferentially associated with specific substances of abuse. We recruited 413 adult ADHD patients, performed an evaluation of their ADHD and conducted an interview on their use of psychotropic substances. Complete data was obtained for 349 patients. Lifetime substance abuse or dependence was 26% and occasional use was 57% in this sample. The inattentive subtype was significantly less likely to abuse or be dependent on cocaine than the combined subtype. Our findings underscore the high rate of comorbidity between substance use and ADHD in adults. The more frequent abuse/dependence of cocaine by adult patients with hyperactive-impulsive symptoms should be kept in mind when treating this patient group. It is characterized by symptoms of inattention (distractibility), hyperactivity, and impulsivity, which all contribute to significant psychosocial impairment in affected individuals of all age groups7. In order to make a diagnosis of ADHD, the two diagnostic manuals, the American Psychiatric Association’s (APA) Diagnostic and Statistical Manual of Mental Disorders Third Edition Revision (DSM-III-R) and the World Health Organisation’s (WHO) International Statistical Classification of Diseases and Related Health Conditions (ICD-10), require the presence of both inattentive and hyperactive-impulsive symptoms9.Attention-deficit/hyperactivity disorder (ADHD) is a complex neuropsychiatric syndrome that is common not only in childhood and adolescence, but in adulthood10 marked a diversion from this route by allowing for a diagnosis of ADHD when either hyperactive-impulsiveor inattentive behaviors were present, and thereby defined three subtypes of ADHD: a) a predominantly inattentive type, b) a predominantly hyperactive-impulsive type, and c) a combined type11. The following years saw a significant amount of research in which the importance of these subtypes in a clinical and epidemiological context was debated. For example, the clinical response to pharmacologic treatment by subtype or symptom clusters was investigated14, as were subtype differences in psychosocial functioning16, and the rate of comorbidity17 in different age groups.In 1994, the introduction of the DSM Fourth Edition (IV)20. Data that stem primarily from clinical and population-based studies suggest that up to 89% of all adults with ADHD suffer from a psychiatric comorbidity during their lifetime16, and that the comorbidity of SUD in adolescents and adults with ADHD might range from 16%–79%23. The heterogeneity of these data is also reflected in research focused on the association between specific ADHD subtypes and SUDs. While some authors find no evidence of such an association, others have concluded that the hyperactive-impulsive subgroup is more likely to suffer from a comorbid SUD than is the inattentive subgroup24.In both pediatric and adult populations, ADHD is significantly comorbid with a wide range of other DSM-IV disorders, irrespective of subtype. The most prevalent of these are mood, anxiety, impulse control, and substance use disorders (SUD)25. The purpose of this study was therefore to characterize a clinical sample of adults with ADHD and to identify possible associations between ADHD subtypes, lifetime substance use, and preferences for specific substances.To our knowledge, few studies have reported on the relationship between ADHD subtypes and SUD in adult samples. Furthermore, the limited data available stems primarily from America, while the few European studies focused on several comorbid factors, not solely on SUD26 between 2002 and 2011, we included adults with a confirmed diagnosis of ADHD and with available information on substance use (N=413). There were no other inclusion or exclusion criteria.Out of all consecutive referrals to the ADHD consultation service of the Zurich University Psychiatric Hospital27, and translated into German and validated for the German language by Rösleret al. and Retz-Jungingeret al.30. The Wender-Reimherr Interview is the German version of the American Wender-Reimherr Adult Attention Deficits Disorders Scale (WRAADDS) for the assessment of adult ADHD. It allows a diagnosis of adult ADHD to be made. It contains seven scales for: attention difficulties, persistent motor hyperactivity, temper, affective lability, emotional overreactivity, disorganization, and impulsivity. Each scale is represented by 3–5 items. A sum score is formed per scale, and each scale has a diagnostic threshold. A diagnosis requires that sum scores for scales 1–2 must each exceed their threshold, and that for scales 3–7, 2 out of 5 sum scores must exceed their threshold. According to DSM-IV Text Revision (TR)31 specifications, three ADHD subtypes were identified: a predominantly inattentive subtype, a predominantly hyperactive-impulsive subtype, and a combined subtype. Subtypes were derived from the Attention Deficit-/Hyperactivity Self-Report Scale (ADHS-SB) questionnaire 33, the Wender Utah Rating Scale (WURS-k)28, and the ADHS-SB34. If patients did not answer all questions on the questionnaire items, they were approached again and asked to supply the missing information. When patients had difficulty answering a question, their therapist helped to clarify it and enable them to provide an answer. In addition, third-party information was sought from family members, spouses, school reports, and childhood medical reports to support the diagnostic procedure.The diagnosis of ADHD was based on the Utah criteria for diagnostic assessment with the Wender Reimherr Interview (WRI)aire see. The ADH9. Subjects reported on the lifetime use of alcohol, opioids, cannabinoids, sedatives, cocaine, (non-cocaine) stimulants, hallucinogens, and tobacco. ICD-10 criteria were applied by a highly experienced clinician (DE) in a semi-structured interview. No official instrument was used. Substance use was differentiated into abuse/dependence and sub-threshold, i.e. non-dependent and non-abusive, but more-than-singular, use. Comorbid disorders were diagnosed according to ICD-10 by DE in a semi-structured interview, again without an official instrument.Assessment of substance use was based on ICD-10 criteria (F10-F19)35.Fisher’s exact tests were used to compare frequency of substance abuse/dependence and comorbidity rates between ADHD subtypes, since small cell sizes were frequent. Kruskal-Wallis tests were used to compare questionnaire scores. Bonferroni correction was applied to all substance-related significance tests. A total of 26 tests were conducted, resulting in a Bonferroni-corrected significance threshold of p ≤.002. P-values surviving this threshold are printed in boldface in the results section. The study has low power: assuming a power of 80%, the minimal detectable difference in substance use frequency among subtypes is between 25–36%, while the power to detect a difference of 10% ranges from 28–48%. Analyses were carried out in Stata 11.2 and Stata 13.1Authorization by the local ethics committee ) was obtained before the study was conducted (04/2005). All participants received a written description of the study procedure and signed a consent form.A total of 64 subjects had no questionnaire data whatsoever and were dropped from further analysis. These “drop-outs” were compared with the remaining 349 subjects and found not to differ in age and gender distribution. Drop-outs more often had affective disorders . They tended to have less overall substance abuse or dependence . Total substance use excluding abuse and dependence was clearly lower in drop-outs .The average age of the included sample was 38.7 years (SD = 11.28), with a gender distribution that was 56% male and 44% female. Other than substance use, the most common comorbidities included affective disorders (25%); neurotic, stress-related and somatoform disorders (15%); and personality disorders (6%).18. A total of 233 subjects were identified as belonging to the combined subtype of ADHD , 70 belonged to the predominantly inattentive type , and 24 belonged to the predominantly hyperactive-impulsive type . WURS-k (p<.04) and ADHS-SB (p<.0001) scores were different between inattentive and hyperactive-impulsive subtypes, while all scores were different at p<.004 for the comparison of inattentive vs. combined subtype.In the sample with questionnaire data  on WURS-k, 28.5 (SD=9.77) on ADHS-SB and 17.6 (SD=7.87) on the newly developed SCL-ADHD scaleAccording to ICD-10 F1x, 26% of all participants at the time of the study, regardless of subtype, fulfilled the criteria for abuse of or dependence on psychotropic substances other than nicotine. The most frequently misused substances consisted of alcohol (8.9%), opioids (6.0%), cannabinoids (8.3%), and cocaine (8.0%). Nicotine abuse/dependence was found in 20.3% of participants.Subtype-specific analyses revealed that 36.9% of the combined subgroup, 44.3% of the predominantly inattentive subgroup, and 41.7% of the hyperactive-impulsive subgroup currently suffered from a comorbid psychiatric disorder. Additionally, 31.3% of the combined-type individuals, 15.7% of the predominantly inattentive subjects and 41.7% of hyperactive-impulsive patients were diagnosed with abuse or dependence on a psychotropic substance other than nicotine.The present study investigated associations between the combined and predominantly inattentive subtypes of adults with ADHD and lifetime substance use, within a clinical sample. The most clinically significant result is the finding that the inattentive subtype showed a statistically significantly smaller rate of cocaine abuse/dependence compared to the combined subtype.et al., who had characterized a sample of 118 adults with ADHD and found that the combined type suffered significantly more from lifetime SUDs (48.4%) than did patients with a predominantly inattentive type (23.3%)16. On the other hand, our findings contrast with results published by Clureet al., who reported on 43 patients with adult ADHD but found no differences in ADHD subtypes when divided by substance of choice 36.These results are in line with earlier work by Sobanski39. With regard to subtype-specific differences, some authors have reported that, at least in young adolescents, the inattentive subtype of ADHD is more likely to correlate with higher levels of nicotine use than does the combined subtype40. It was suggested that nicotine might primarily improve attention but have less influence on hyperactive-impulsive behavior, which might explain this finding42. Other researchers, however, suggest that hyperactive-impulsive symptoms present a greater risk for frequent nicotine use than do inattentive symptoms at a later age, and argue that the relationship between ADHD symptoms and nicotine use might change between adolescence and adulthood43.The most frequently consumed substance among all study participants was nicotine. This finding is in accord with results from prior studies45. In this sample, however, we found no evidence for this assumption, but lack of statistical power precludes interpreting this as evidence of no difference. We suspect that adults with both hyperactive-impulsive and inattentive symptoms might initially prefer cocaine to stimulants for self-medication, but there is no direct evidence for this assessment48.Our hypothesis that findings would show continuing preferences for the use of specific substances in adulthood according to subtype (beyond cocaine), remains open due to lack of statistical significance. Like earlier reports of (non-cocaine) stimulants being used as self-medication by patients with ADHD, we had also expected to find a higher rate of non-prescribed lifetime stimulant abuse/dependence in the hyperactive-impulsive type, but not in the inattentive one50. More recently, Sauleset al. compared the symptom profile among adult ADHD smokers with and without cocaine dependence, and found that when they corrected for the use of nicotine, adults who used cocaine exhibited a more severe adult ADHD symptom profile, as accounted for by the presence of elevated hyperactive-impulsive but not inattentive symptoms. He therefore suggested that cocaine use in smokers with ADHD might be driven by excesses in hyperactivity50. Despite differences in sampling, our results are in accord with this finding.The possibility of using cocaine as an attempt to self-medicate for ADHD symptoms was originally proposed in the early ’90s51.On a different note van Wingen et al investigated structural brain abnormalities in this population and reported of significantly smaller grey matter volumes in the occipital cortex as well as smaller volumes in the putamen in ADHD patients with comorbid cocaine dependence when compared to those without this lifetime diagnosis. The authors of aforementioned study suggested that the differences in putamen volumes may reflect alterations in the availability of striatal dopamine transporters that are available for interaction with methylphenidate, thus giving some explanation for the finding that methylphenidate is less effective in patients with ADHD and a comorbid cocaine dependence52. However in this sample that relied for diagnosis of comorbidity on a semi-structured clinical interview, but not on additional instruments, we found only 6% of patients suffering from a comorbid personality disorder. This is low in comparison to some studies reporting prevalence rates between 25 – 78%57.The main limitation of this study is low power. This means, in particular, that non significant findings cannot be interpreted as evidence of no difference. A further limitation is that our sample was recruited entirely within a university setting, which might contribute to a selection bias. As a result, this clinical sample might have different characteristics than patients would exhibit who are in treatment with a physician in private practice. Nevertheless, the ADHD consultation service of the Psychiatric University Hospital Zurich is the largest institution of its kind in Switzerland and attracts patients from diverse psychosocial backgrounds. Furthermore comorbidities, particularly personality disorders might have confounded the results. For instance, Borderline personality disorder, which often co-occurs with ADHD and is difficult to differentiate, is also known to be associated with SUD58. Furthermore a study among patients with ADHD and a comorbid cocaine dependence receiving methylphenidate, demonstrated an advantage over placebo with regard to reduction in cocaine use in individuals who responded to ADHD treatment60.In conclusion, our findings underscore the high rate of comorbidity between substance use and ADHD in adults. The more frequent abuse/dependence of cocaine by adult patients with hyperactive-impulsive symptoms should be kept in mind when treating this patient group. Although a limited number of evidence-based treatment strategies currently exist for the concurrent treatment of ADHD and SUD, some studies suggest that stimulant medication remains an efficacious pharmacological treatment option that improves symptoms of ADHD without increasing the likelihood of relapse into SUDThe data referenced by this article are under copyright with the following copyright statement: Copyright: © 2016 Liebrenz M et al.et al., doi:10.5281/zenodo.1962361ZENODO: Dataset 1. Contains all the variables necessary to reproduce the results of Adult attention-deficit/hyperactivity disorder: Associations between subtype and lifetime substance use – a clinical study, Liebrenz62ZENODO: Stata source code to reproduce analysis, doi: 10.5281/zenodo.19622Written informed consent was obtained from patients. The authors list multiple clinical scales used to assess ADHD and state that SUD was assessed based on ICD-10 criteria. Like the Freiburger reviewers, the first question that occurred to me was whether any standardized instrument was administered to assess SUDs?Again, as asked by other reviewers, were the patients in the sample undergoing current pharmacological treatment? Presumably, many were on methylphenidate or other agents.It would be a good idea to cite some statistics for prevalence substance abuse and dependence in the general population around Zürich. Then the reader would have an idea how much higher prevalence is in the adult ADHD clinical sample.p-values ≤ 0.002, based on Bonferroni correction for multiple comparisons. It might be informative to discuss some of the other results that would have been significant under a less stringent cut-off. For example, nicotine abuse/dependence is twice as frequent and alcohol abuse/dependence is nearly ten times as frequent in the Combined as in the Inattentive subgroup. These may be worth commenting on. But I wouldn’t discuss any comparisons involving the Hyperactive-Impulsive subgroup, since they are too few (only 24 subjects).The investigators were commendably conservative in claiming significant results, restricting themselves toIn the Introduction, the authors retell the diagnosis and subtyping of ADHD in DSM-III-R, ICD-10, and DSM-IV. They should add a line or two about DSM5, just to round out their brief historical review.The investigators determined the effect of ADHD subtype on the prevalence of substance use disorders (SUDs) in a large (413 patients) sample of (medicated?) adult ADHD. In line with expectations, the overall sample evinced high rates of lifetime substance abuse or dependence (26%) and occasional use (57%). The inattentive subtype was significantly less likely to abuse or be dependent on cocaine than the combined subtype. As indicated by the Bordelais reviewers, while not a major advance, this study is a perfect example of normal science in the sense of Kuhn and represents a worthwhile gain in our knowledge of ADHD.I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. The paper "Adult attention-deficit/hyperactivity disorders: Associations between subtype and lifetime substance use – a clinical study” covers, besides the well-known comorbidity of ADHD with substance use disorders (SUDs), a very interesting field of research concerning the associations between ADHD subtypes and substance use disorders. It adds to the knowledge and differentiates knowledge in focusing on ADHD subtypes. Particularly we noted the large sample size, as it allows more reliable results, the valid assessment of ADHD by using standardized instruments and third-party information and the well detailed statistical analysis. The applied methods appear overall reasonable and valid to us. The authors mentioned that assessment of substance use was based on ICD-10 criteria. However they didn’t exactly explain their method to gather this data. We noted here the lack of standardized instruments. Furthermore they pooled substance abuse and dependence in one category. The rational for using this procedure should be given in more detail.We missed information about psychopharmacological treatment. This information might provide potential correlations of treatment/no treatment with substance use.1 is also known to co-occur with SUD. Further, we wonder that only 6% of the patients had a comorbid personality disorder, which is low in contrast to some studies reporting prevalence rates of personality disorders between 25% and 78% among individuals with ADHD2-5.  It is also important to make clear, how the authors assessed comorbid disorders. Did they use standardized instruments?Another question regards the comorbid disorders: It should be discussed that comorbidities, particularly personality disorders might have confounded the results. For instance, Borderline personality disorder, which often co-occurs with ADHDThe sample size of 327 represented on Table 1, page 4, does not correspond to the described sample size in the paragraph above “Results” . In the discussion it might be interesting to explain the use and effects of cocaine among individuals with ADHD, especially with regard to neurobiology. It would also be interesting to know about possible hypotheses and assumptions among the authors concerning the subtype difference in cocaine abuse/dependence. Are there neuropsychological or clinical differences between the subtypes which protect the inattentive subtype from cocaine dependence?The discussion should also comment on the relevance of the presented findings for therapeutic approaches. We have some remarks that should be addressed:We have read this submission. We believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. We appreciate the dedicated and useful comments of Dr. Swantje and Dr. Hoxhaj and the editor and the chance they gave us to improve the manuscript.ICD-10 criteria were applied by a highly experienced clinician (DE) in a semi-structured interview. No official instrument was used.Estimates of percentages would have been small  and noisy if we had separated dependence and abuse. Combining them gives a more robust estimate and seems justified to us also because both describe a serious level of substance use that requires treatment.The reviewer asks us to elaborate on how ICD-10 criteria for substance use were assessed and why abuse and dependence were pooled.The reviewer asks for information on psychopharmacological treatment. Unfortunately, such information is not available.The reviewer asks us to discuss and to clarify assessment of comorbidities.“Comorbid disorders were diagnosed according to ICD-10 by DE in a semi-structured interview, again without an official instrument.” and “Furthermore comorbidities, particularly personality disorders might have confounded the results. For instance, Borderline personality disorder, which often co-occurs with ADHD and is difficult to differentiate, is also known to be associated with SUD. However in this sample that relied for diagnosis of comorbidity on a semi-structured clinical interview, but not on additional instruments, we found only 6% of patients suffering from a comorbid personality disorder. This is low in comparison to some studies reporting prevalence rates between 25 – 78%.” We have addressed these questions in the Methods and in the Discussion (Limitations) Section. We now state:The  N=327 reflects the fact that not all patients diagnosed with ADHD fulfilled subtype criteria. Remember that in this study, ADHD was diagnosed according to Utah (Wender-Rheimherr), not DSM, criteria, and subtypes were constructed post-hoc using scores on the ADHS-SB questionnaire. This means that the diagnosis itself does not necessarily entail a subtype assignment, and vice versa. Thus,  in about 20 participants ADHS-SB scores were not high enough to yield a subtype classification. This is now explained in the methods section under the heading "Assessment of ADHD symptomatology".On a different note van Wingen et al investigated structural brain abnormalities in this population and reported of significantly smaller grey matter volumes in the occipital cortex as well as smaller volumes in the putamen in ADHD patients with comorbid cocaine dependence when compared to those without this lifetime diagnosis. The authors of aforementioned study suggested that the differences in putamen volumes may reflect alterations in the availability of striatal dopamine transporters that are available for interaction with methylphenidate, thus giving some explanation for the finding that methylphenidate is less effective in patients with ADHD and a comorbid cocaine dependence.”The reviewer suggests to discuss the use and effects of cocaine among individuals with ADHD, especially with regard to neurobiology. We have addressed these aspects in an expanded discussion section. We now state: “Furthermore a study among patients with ADHD and a comorbid cocaine dependence receiving methylphenidate, demonstrated an advantage over placebo with regard to reduction in cocaine use in individuals who responded to ADHD treatment.”The reviewer asks us to comment on the relevance of the presented findings for therapeutic approaches. We now point towards research by Levin et al and have expanded the conclusion section: “   et al. addressed the association between Adult attention-deficit/hyperactivity disorder (ADHD) subtypes and lifetime substance-use disorders (SUD). This topic is of particular interest , as there is a strong literature supporting a relationship between ADHD and SUD (Wilens 2004). An emerging issue is the relationship between SUD and ADHD subtypes . For instance, Tammet al. found more severe SUDs for the Combined subtype . Our team suggested that Combined and Inattentive subtypes might be associated with more severe addictive disorders . As stated in the manuscript, other authors reported the Hyperactive-impulsive subtype more likely to be associated to a comorbid SUD, or no difference. Data remains limited and this topic is still in debate.In this clinical study, Liebrenz et al. conducted a cross sectional study with validated questionnaires assessing ADHD symptomatology and substance use, among 413 adults diagnosed with ADHD. They hypothesized that results would show statistical differences of lifetime SUD prevalence for specific substances, according to ADHD subtype. The main finding of this study was that the Inattentive ADHD subtype was significantly less associated than the Combined subtype to lifetime cocaine abuse/dependence (there was no difference for other substances). However, Hyperactive-impulsive and Inattentive subtypes were not statistically different for their association to any substance disorder.In this perspective, Liebrenzet al.’s work is a significant contribution – but not a breakthrough – to research on the relationships of ADHD subtypes and addiction. As reviewers, we noted the clarity of their manuscript, the justification of the study and the definition of their purpose in the introduction section. The method seemed valid to us and missing data (64 subjects) were correctly managed. However, we think that the strategy of analysis should have been more detailed in a specific paragraph. For instance, the usefulness of the WURS-K questionnaire is not explained. The Wender Reimherr Interview (WRI) and the Attention Deficit-/Hyperactivity Self-Report Scale (ADHS-SB) would also have deserved a short presentation and explanation of their use in this study. Another point to argue is the choice of the WRI to diagnose ADHD, as Rosleret al. (2006) stated that “on the basis of the WRI, DSM-IV diagnoses cannot be made”, even if “considerable amount of overlap exists” .Liebrenzet al 2013). The authors might clarify this use of ICD-10 in a DSM 5 perspective. The ICD-10 substance use categories might have allowed a more specific study of the association of addiction and ADHD-subtypes?Results are presented and discussed appropriately. The authors mentioned that assessment of substance use was based on ICD-10 criteria. However, for their analysis they pooled substance abuse and dependence in one category without giving the rationale for that choice. In ICD-10 and DSM-IV these are distinct entities. However, in DSM 5 these distinct categories have been combined with other adjustments into one unique category  and the Attention Deficit-/Hyperactivity Self-Report Scale (ADHS-SB). We have now added the following two paragraphs on these tests: WRI: "The Wender-Reimherr Interview is the German version of the American Wender-Reimherr Adult Attention Deficits Disorders Scale (WRAADDS) for the assessment of adult ADHD. It allows a diagnosis of adult ADHD to be made. It contains seven scales for: attention difficulties, persistent motor hyperactivity, temper, affective lability, emotional overreactivity, disorganization, and impulsivity. Each scale is represented by 3–5 items. A sum score is formed per scale, and each scale has a diagnostic threshold. A diagnosis requires that sum scores for scales 1–2 must each exceed their threshold, and that for scales 3–7, 2 out of 5 sum scores must exceed their threshold." ADHS-SB: " The ADHS-SB is a self-rating instrument for the assessment of adult ADHD in German.  It consists of 18 symptoms of ADHD derived from the DSM-IV and ICD-10 criteria for ADHD. The degree of endorsement is rated on four levels: 0 = not at all, 1 = slightly, 2 = moderately, and 3 = severely. The total score is obtained by summing up the 18 individual item scores. Subsyndrome scores for ‘‘attention deficit’’, ‘‘hyperactivity’’, and ‘‘impulsivity’’ can also be obtained." adult ADHD, while the WRI is specifically targeted to adults. As Rosler also states "the question remains whether the DSM-IV criteria are adequate to characterize adult ADHD" (p. I/4) and "An advantage of the WRI could be the extended spectrum of adult psychopathology" (p. I/10). There is certainly room to argue for either diagnostic approach. Reassuringly, as the reviewers also note, the two approaches show considerable overlap.  3. The reviewers question the choice of the WRI to diagnose ADHD, stating that according to Rosler et al. (2006), DSM-IV diagnoses cannot be made based on the WRI. This is true. However, the DSM-IV does not contain a specific diagnosis for 4.The reviewers ask for the rationale for pooling substance abuse and dependence. The reason is primarily statistical: estimates of percentages would have been small and noisy if we had separated dependence and abuse. Combining them gives a more robust estimate. This also seems justified to us because both abuse and dependence describe a serious level of substance use that requires treatment.


Furthermore, among females, ADHD was associated with Crohn’s disease, adjOR = 1.44 (1.16–1.79) and ulcerative colitis, adjOR = 1.28 (1.06–1.54). In contrast, males with ADHD had lower odds of Crohn’s disease, adjOR = 0.71 (0.54–0.92), in addition to a trend for lower odds of ulcerative colitis, adjOR = 0.86 (0.71–1.03); p values for interaction < 0.0001 and 0.0023, respectively. In a group of females where information on smoking and body mass index was available, adjustment for these potential mediators did not substantially alter the associations. Our findings support previously reported associations between ADHD and diseases of the immune system. The associations differ by sex, suggesting that sex-specific immune-mediated neurodevelopmental processes may be involved in the etiology of ADHD.Several studies have demonstrated associations between neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD), and the immune system, including autoimmune diseases. Since ADHD and many autoimmune diseases show sex-specific properties, such associations may also differ by sex. Using Norwegian national registries, we performed a cross-sectional study based on a cohort of 2,500,118 individuals to investigate whether ADHD is associated with common autoimmune diseases. Associations between ADHD and autoimmune diseases in females and males were investigated with logistic regression and effect modification by sex was evaluated. Several subanalyses were performed. The strongest association was found between ADHD and psoriasis in females, adjusted odds ratio (adjOR) = 1.57  and males, adjOR = 1.31 (1.23–1.40); The online version of this article (doi:10.1007/s00787-017-1056-1) contains supplementary material, which is available to authorized users. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by the symptoms of inattention, hyperactivity and impulsivity. The symptoms of this childhood onset condition often persist into adulthood . FurtherST3GAL3 [ST3GAL3 gene affects both eosinophilic immune responses [Numerous studies have reported associations between neuropsychiatric disorders and immune system abnormalities –16. HoweST3GAL3 . Knockouesponses  and braiesponses .ADHD has an approximate male:female ratio of 3:1 during childhood and adolescence, which approaches 1:1 in adults . For exaIn sum, if sex-specific genetic pleiotropy, or other sex-specific mechanisms, underlie any associations between ADHD and autoimmunity, these associations may differ substantially by sex. In other words, sex could be an effect measure modifier.To further explore possible associations between autoimmunity and ADHD, and to evaluate whether these associations vary by sex, we conducted a large cross-sectional study based on Norwegian national registries.The Medical Birth Registry of Norway (MBRN) was established in 1967 to collect medical and familial information on parents and births in Norway . RegistrData for the current study was obtained for all live births in the MBRN from January 1st 1967 to December 31st 2013.The Norwegian Prescription Database (NorPD) was established in 2004 and provides information on all medical prescriptions dispensed to patients from all Norwegian pharmacies, and includes the Anatomical Therapeutic Chemical Classification System (ATC) codes . InformaFor the present study, information was obtained for all dispensed drugs between January 1st 2004 and December 31st 2015.The National Education Database holds information on the education of all Norwegian citizens from the age of 16 years. The database covers all levels of education from primary school to PhD-level. For the present study, data on education as registered in 2012 was available.The National Registry supplied information on emigration and dates of death.All individuals registered in the MBRN as born between 1967 and 2011, who were alive and residing in Norway on December 31st 2015, were included in the study. In addition, the mothers of those registered in the MBRN between 1998 and 2013, were identified for supplementary analyses allowing adjustment for body mass index (BMI) and smoking. Mothers who had died or emigrated by December 31st 2015 were excluded from these supplementary analyses (see below).All Norwegian citizens have a unique personal identification number. This number was used to establish linkage between the registries.n = 63,721), without reimbursement codes for “narcolepsy”, G47 in ICD-10 and “sleep disturbance”, P06 in ICPC (n = 407), during 2004–2015.ADHD cases were defined as all individuals, regardless of age, who had been dispensed reimbursed ADHD medication (ATC N06BA) .The remaining population served as the comparison group  to p = 0.0056. The threshold for nominal significance was defined as p = 0.05. Data management and statistical analyses were performed with R [Possible associations between ADHD and the autoimmune diseases were estimated as odds ratios (OR) with 95% confidence intervals (CI) using logistic regression. d with R , RStudiod with R  and IBM d with R .In the primary analyses, associations between autoimmune diseases and ADHD were investigated with adjustment for age as a continuous covariate, except for type 1 diabetes where age was categorized into four . All analyses were stratified by sex –34. EffeSocioeconomic status as defined by maternal education was adjusted for as a categorical covariate with three categories, low (< 10 years of education), medium (10–12 years) and high (> 12 years).Statistically significant associations in the primary analyses were further investigated in supplementary analyses concerning potential confounders, mediators and biases.2) of the mothers was used. Mothers with registered height below 130 cm or BMI below 15 or above 60 were set to missing as these values were considered biologically implausible. Socioeconomic status was defined as the education of the mother in 2012 categorized into three: low (< 10 years), medium (10–12 years) and high (> 12 years). For females who had given birth to several children, only data from the last registered birth was included.Tobacco smoking and BMI may be mediating factors between ADHD and autoimmune diseases. Smoking is known to be associated with ADHD , 48 and Logistic regression was used to investigate associations between ADHD and autoimmune diseases among these mothers with and without adjustment for the mother’s smoking habits and with education as covariate. Further, a similar logistic regression was conducted with the inclusion of BMI, modelled as a continuous covariate, in addition to smoking and education. Substantial attenuation of the estimated associations between ADHD and autoimmune diseases when adjusting for smoking and BMI, would indicate that much of the effect of ADHD on these diseases might be mediated through these mediators , 58.Several additional subanalyses were also conducted, when possible, to scrutinize statistically significant associations identified in the primary analyses .We identified a total of 2,500,118 individuals in the MBRN fulfilling our inclusion criteria for the primary analyses, 1,219,669 females and 1,280,449 males.22,878 (1.9%) of the females had ADHD with the highest prevalence among those born in 1993 (3.5%). Of the males, 40,843 (3.2%) had ADHD, with the highest prevalence among those born in 1996 (6.8%) . ADHD was associated with lower socioeconomic status, as defined by maternal educational level  for systemic lupus erythematosus (SLE) to 62,418  for psoriasis. The female-to-male ratios varied across the autoimmune diseases, with 42.3% of type 1 diabetes patients being female, to 85.5% of SLE patients. All autoimmune diseases increased in prevalence with age . All autoimmune diseases were associated with lower socioeconomic status.p value for interaction by sex = 4.4 × 10−6.ADHD was significantly associated with increased odds of psoriasis in both females, adjusted (adj) OR = 1.57 (95% CI 1.46–1.68) and males, adjOR = 1.31 (95% CI 1.23–1.40). Associations were significantly stronger for females than males, p = 3.6 × 10−5, and UC, p = 0.0023. Despite not reaching the threshold for statistical significance, UC was taken to supplementary analyses as UC shares many characteristics with CD and displayed statistically significant interaction effects by sex.Sex differences were even larger for Crohn’s disease (CD) and UC: Females with ADHD had a significantly higher odds of CD, adjOR 1.44 (95% CI 1.16–1.79), and UC, adjOR = 1.28 (95% CI 1.06–1.54), than females without ADHD. Males with ADHD, on the other hand, seemed protected, with a lower odds of CD than males without ADHD, adjOR = 0.71 , and a tendency to lower odds of UC, adjOR = 0.86 (95% CI 0.71–1.03). There were significant interaction effects between ADHD and sex on the odds for both CD, p = 0.021.ADHD was further associated with lower odds of ankylosing spondylitis among females, but only at nominal statistical significance, adjOR = 0.56 (95% CI 0.32–0.96). No association was found for males, adjOR = 1.16 (95% CI 0.87–1.55). A nominally significant interaction effect between ADHD and sex was noted, The primary analyses were also adjusted for prematurity, gestational age ≥ 37 weeks or < 37 weeks, with little effect on the results (data and results not presented).See Table 512,957 females gave their last birth between December 1998 and December 31st 2013 during which time smoking habits were registered in the MBRN. Of these, 373,672 (72.8%) were themselves also registered in the MBRN at their own birth. There was information on educational level for 497,005 (96.9%) of the mothers, and of these, information on smoking for 420,050 (84.5%). Of these 420,050, 73,891 (17.6%) were defined as smokers, and additional information on pre-pregnant BMI for was available for 110,008 (26.2%). The mean and standard deviation of pre-pregnant BMI was 24.4 and 4.8, respectively, and 13,304 (12.1%) of these 110,008 females were defined as smokers. Thus, data on educational level, smoking and BMI was available for 21.4% of all females delivering their last recorded birth since the introduction of smoking information in December 1998 and up to December 31st 2013. See supplementary Fig. 2 for flowchart.In the mother analyses, ADHD was associated with increased odds of psoriasis, adjOR = 1.62 (95% CI 1.44–1.81) also after additional adjustment for smoking, adjOR = 1.49 (95% CI 1.33–1.67) and BMI, adjOR = 1.29 (95% CI 1.04–1.60).ADHD was associated with CD, adjOR = 1.77 (95% CI 1.23–2.54) and UC, adjOR = 1.87 (95% CI 1.42–2.46). Adjustment for smoking did not materially change ADHD’s association with CD, adjOR = 1.63 (95% CI 1.13–2.34) nor UC, adjOR = 1.90 (95% CI 1.45–2.50). Similarly, additional adjustment for BMI did not alter the ADHD-CD association, adjOR = 2.20 (95% CI 1.24–3.88) nor the ADHD-UC association, adjOR = 2.10 (95% CI 1.30–3.39).Similar analyses stratified by smoking and overweight, BMI < 25 or ≥ 25, were also conducted. The results were in line with the presented findings (data and results not presented). See Table As a robust positive association between psoriasis and ADHD was identified, this association was further examined, both in regards to psoriasis case definition and age- and period effects. The supplementary analyses confirmed the results of the primary analyses .The diagnoses CD and UC partly overlapped as 2334 individuals in the primary analyses were defined as having both conditions (37.1% of the CD patients and 21.3% of the UC patients). Supplementary analyses were conducted after redefining all individuals with both CD and UC as having neither. The results confirmed the positive associations in females, and the interaction by sex, but the negative associations in males were now not present . To assess age- and period effects of ADHD on CD and UC, analyses stratified on birth years, 1967–1985 and 1986–2011, were conducted. For CD, the results were in line with the main analyses for both individuals born 1967–1985 and those born 1986–2011, including the sex-effects. However, for UC, the positive association in females, and negative association in males, were only noted in those born 1967–1985. For those born 1986–2011, no associations were noted .In our large cross-sectional study based on population-wide registries, ADHD was clearly and positively associated with psoriasis. This association was present regardless of sex, but with a significantly stronger association in females than males. Furthermore, in females, ADHD was positively associated with CD and UC. In contrast, among males, ADHD showed a negative association with CD, and a similar tendency with UC.p = 0.09), which may be due to the study’s prospective study design where the autoimmune diseases had to debut prior to ADHD. In contrast, we utilized a cross-sectional design. Moreover, we investigated both children and adults, 4–48 years of age at linkage, whereas the Danish study only examined children and young adults, 5–22 years old at linkage, which lead to a smaller study sample. In addition, many of the individuals in the Danish study were simply too young to have developed psoriasis [Psoriasis is a skin disorder characterized by red scaly skin plaques, papules or patches and is generally considered an autoimmune disease . The etisoriasis  or to hasoriasis .Several different mechanisms may account for the association between ADHD and psoriasis. A recent family-based epidemiological study reported a significant genetic correlation between ADHD and psoriasis , indicatCD and UC are both diseases primarily affecting the gastrointestinal system . They arThe increased odds of CD and UC in females with ADHD, with a reverse relation in males is striking. In addition, ADHD females had significantly higher odds of psoriasis than ADHD males. Sex, including both hormonal and non-hormonal influences, is a key determinant of immune system functioning , 34, braGenetically, pleiotropic associations between psychiatric disorders and autoimmune diseases have been reported , and so Alternatively, smoking and BMI may play a role in the sex-discordant associations between ADHD and IBD , 52, 56.It could be that living with ADHD as a female gives rise to more stress, for example through social expectations and cultural norms, which again might lead to more autoimmunity , 65 and Our study has several strengths. The use of compulsory population-wide registries minimize the risk of selection bias, and may provide the statistical power needed to investigate potential associations between ADHD and different autoimmune diseases. Further, the compulsory registration of prescription data protects against follow-up bias. However, we do not have information on medication given to hospital inpatients and nursing homes. Considering that the individuals in the primary analyses were all under 50 years, and that chronic diseases were investigated, we assume these factors to be of minor importance.Another strength is the possibility to adjust for smoking and BMI in the mother analyses to assess mediating effects. However, we make the assumption that BMI and smoking at last registered pregnancy is “representative” of lifetime status up to 2015, which is sub-optimal. As the mother analyses were based on females, the generalizability to males could be questioned. Nonetheless, we consider it biologically unlikely that the positive association between psoriasis and ADHD is mediated purely by smoking and BMI in males, but not in females. In addition, several types of bias may occur as the mother analyses were based on only females who had given birth, and many autoimmune diseases are associated with reduced fertility , again pIn Norway, the prescription of medication used in the treatment of ADHD is restricted and the drugs are only prescribed after thorough diagnostic evaluation in specialist health care. ADHD patients as defined by dispensed drugs is therefore presumably specific for ADHD. Nonetheless, we have missed patients who used ADHD medication only prior to 2004, and those who have never been prescribed medications due to contraindications, mild symptoms or patients who declined pharmacological treatment. However, a previous study using similar data from the same period, demonstrated that only 17% of registered ADHD patients had not received ADHD medication . FurtherDispensed medication and reimbursement codes (ICD-10 codes and ICPC codes as indications for dispensed medication) were used as proxies for autoimmune diseases. Thus, our definitions of autoimmune diseases may not capture all patients. For example, patients with primary-progressive multiple sclerosis, which constitute 10–15% of multiple sclerosis patients, will often not be identified by our approach as until recently there have been limited pharmacological treatment options for this group . FurtherWe found no robust statistically significant associations between ADHD and the autoimmune diseases iridocyclitis, rheumatoid arthritis, SLE, ankylosing spondylitis, multiple sclerosis or type 1 diabetes. This could be due to a genuine lack of association between these autoimmune diseases and ADHD. Nonetheless, it could be that the low share of individuals born prior to 1990 who have dispensed ADHD-medication  as compared to those born later, may reflect ADHD symptom remission before 2004 when the NorPD was established, or historical underdiagnosis and undertreatment of ADHD. Consequently, these ADHD individuals are not identified by our case definition. On the contrary, many autoimmune diseases are diagnosed later in life. Combined, our study may be inadequate for discovering associations between ADHD and autoimmune diseases with late debut. This may also partly explain the absence of any associations between ADHD and UC among individuals born 1985–2011 .As our study is cross-sectional and we exclude all deceased or emigrated individuals, this may constitute a source of bias as ADHD is associated with increased mortality  and so aAnother source of bias could be that ADHD patients, already in contact with the health services, may get a diagnosis of comorbid diseases more easily than individuals who do not have an established link with the health services. However, one should then expect increased odds of all autoimmune diseases, and for both females and males, which was not the case. The symptoms of an autoimmune disease could also be mistaken for ADHD symptoms. For example the itch of psoriasis could lead to lower sleep quality and daytime sleepiness , 78, whiIn conclusion, our study supports previous reports on associations between ADHD and autoimmune diseases, and adds new knowledge about sex-specific associations and even reverse direction by sex for some associations. Our results also suggest that these associations are not mediated by smoking or BMI. Overall, our study suggests that sex-specific immune-mediated neurodevelopment may play a role in ADHD etiology, warranting further investigation. Future studies investigating the relationship between autoimmunity and neuropsychiatric disorders should be aware of sex-specific effects.Supplementary material 1 (DOCX 44 kb)Supplementary Fig. 1 Birth year and sex-specific prevalence rates for ADHD and the autoimmune diseases investigated in the primary analyses (PDF 16 kb)Supplementary Fig. 2 Flowchart of inclusion in the mother analyses (PDF 23 kb)Below is the link to the electronic supplementary material.


Histoplasma capsulatum, Coccidioides spp., Blastomyces spp. or Sporothrix spp., compared to more than 20,000 publications about Saccharomyces cerevisiae. Although there are many reasons for this, the disparity indicates the need for more information about primary pathogenic fungi as well as model fungal organisms. Special issues such as this attempt to address this disparity.This special issue, “Genomic Data in Pathogenic Fungi,” focuses on the genomics of human and plant pathogens. Efforts like this are important because so little information about these organisms is available. There are fewer than 350 publications in the PubMed database reporting genomic data of filamentous fungi that are primary human pathogens, such as Fusarium colmorum with respect to rye head blight and provide vital information about fungal pathogenesis. The authors use a combination of quantitative trait locus mapping and SNP calling to identify an SNP associated with the ability to cause disease in rye. This SNP, upstream of the secreted cutinase, is required to penetrate plant cuticles and presumably affects transcription of the cutinase gene, although transcription studies in such highly pathogenic and less pathogenic strains will be important to confirm these data.Castiblanco et al.  describeUnderstanding the fungal cell wall is a critical component of understanding fungi and their pathogenic potential. A large-scale comparison of the cell-wall-related components of multiple pathogenic fungi is one way to understand them. Muszeska et al.  identifyCoccidioides spp., important human pathogens in the desert regions of the new world. LTR/Gypsy transposons are the most common in Coccidioides spp.; most of them have degenerated and lack some of the coding regions required for transposition. Although most transposons are found in gene-poor regions, the genes that are flanked by transposons tend to be expressed at an average level that is lower than that of all genes, especially in C. immitis. Genes coding for protein phosphorylation tend to be over-represented in the genes flanking transposons in both C. immitis and C. posadasii. The biological significance of these observations is not yet clear.Non-protein encoding genomic transposable elements are important for epigenetic phenomena. All fungi contain transposons, but the number and type of such transposons vary substantially between taxa. Kirkland et al.  characteDealing with large amounts of data and extracting biologically meaningful insights is always a challenge. Basenko describes FungiDB , an onliImproving our understanding of primary pathogenic fungi will require thoughtful experiments and data analysis. It is hoped that this special issue can make a small contribution to this effort.


Emotional dysregulation is increasingly recognized as a core feature of attention-deficit/hyperactivity disorder (ADHD). The purpose of the present systematic literature review was to identify published data related to the neuropsychology of emotional dysregulation in children with ADHD. The literature obtained is discussed in the contexts of deficits in emotional control, impairments in executive function, the emotional components of comorbidities, neurophysiological and autonomic correlates of emotional dysregulation, and the significance of multiple neuropsychological pathways of ADHD on emotional dysregulation. These various lines of evidence are used to create a patient-oriented conceptual model framework of the pathway from stimulus to inappropriate internalized  or externalized  emotional responses. The article concludes by calling for continued research into the development of reliable and universally accepted measures of emotional dysregulation in order to provide children affected with ADHD, and their caregivers, some explanation for their emotional lability and, ultimately, to be used as tools to evaluate potential treatments. Barry is a 10-year-old boy with attention-deficit/hyperactivity disorder (ADHD) who has been suspended from school. His father stays at home with him, but insists that Barry does a number of homework exercises. Barry understands the necessity and is doing the work, but becomes increasingly frustrated by the amount of work. Barry thinks he is doing the last exercise when his father indicates there is one more page of math to do. Barry’s heart starts to beat a little faster and he feels agitated. Just then the telephone rings; it is the school principal wishing to speak to Barry’s father about the suspension and reintegration process. Barry can hear only a little of the conversation but, already agitated, he becomes increasingly angry. His blood pressure rises, his face turns red, and he begins to throw things, first around his bedroom and then around the house. He yells and screams, disrupting the telephone call, and strikes out at his father in desperation. Finally, he retreats to his bedroom, destroying things along the route.Equally, consider Rachel, a 7-year-old girl with the inattentive presentation of ADHD. Rachel is frustrated with not understanding some homework on which she is working. She feels overwhelmed by a project that is due in a few days. Rachel has kept her emotions inside, and her mother is not aware of her frustrations. Her mother asks her to clear the dinner table. Rachel does not respond at first, but when her mother asks her again, Rachel bursts into tears stating that her mother is always demanding so much of her.Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5)  AND ) AND (regulation OR dysregulation))) AND Humans[Mesh] AND English[lang])) NOT review[Publication Type]) NOT adult. Articles were required to contain data related to the neuropsychology of emotional dysregulation in children with ADHD. Reviews, case studies, and commentaries were excluded, as were articles that were not specifically related to ADHD and emotional dysregulation . The search strategy is described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram   and the severity of symptoms of ADHD was provided using the Rorschach inkblot method , exploratory study in children (aged 8–11 years) with ADHD, parents reported data about their child’s emotional status three times daily  for 28 days  with outcomes correlated with those of the emotion regulation checklist, the child behavior checklist, and the Children’s Depression Inventory 2nd Edition supporting the validity and utility of the parent-reported EMA  parallel study did not support the validity of child-reported EMA, perhaps because self-report was problematic in emotionally distressed children  utilizes a handheld device both to prompt parents to enter assessments of their child’s emotional state and to receive them and, therefore, has the potential to assess both discrete and temporal facets of emotional dysregulation. In a small  with ADHD and/or impaired executive function , anxiety disorder (n = 24), ADHD with comorbid anxiety disorder (n = 11), and a healthy control group. ADHD was associated with impairments on the inhibit, emotional control, and working memory elements of the BRIEF , combined-type ADHD (n = 21), Asperger syndrome (n = 15), and controls (n = 32)  is a generic instrument used to assess executive function in children and adolescents with ADHD  were followed up 10 years later  or without (n = 32) ADHD led to the hypothesis that emotional dysregulation may link ADHD in childhood with the development of depression in later life  and healthy controls (n = 19) was evaluated using functional magnetic resonance imaging (fMRI)  of amygdala circuits, and emotion regulation deficit in children aged 6–13 years with ADHD (n = 10) and typically developing controls (n = 16) using a combination of psychosocial  and physiological [electroencephalographic event-related potentials (ERPs)] measures during the administration of the Go/No-Go task (Wiersema and Roeyers n = 31) compared with controls without ADHD (n = 32)  and typically developing controls (n = 34), physiological recordings were conducted during a task that required participants to view an emotion-laden film while mimicking (induction) or masking (suppression) the emotion of the main character , those with ADHD with developmentally appropriate prosocial behavior (n = 54), and typically developing children (n = 75)  is the natural variation in heart rate that occurs during breathing, whereby heart rate increases during inhalation and decreases during exhalation and is an indirect biomarker of vagal tone. RSA is particularly pronounced in children, and abnormal RSA has been linked to emotional dysregulation in childhood psychopathologies  with ADHD during three conditions  , without ADHD (n = 52), or with borderline or not otherwise specified ADHD (n = 35)  and controls  using assessments of executive function , delay aversion, reaction time variability, and emotion regulation and recognition  with ADHD (n = 22) or without (n = 20) ADHD. Neural connectivity in neural circuits underlying executive function and emotional regulation was found to be reduced in participants with the disorder compared with controls  indicate that the processing of emotional stimuli is impaired in ADHD. Most descriptions of emotional dysregulation in ADHD include the concepts of an inability to modulate emotional responses and excessive reactions to a particular emotional trigger that would be considered inappropriate for the developmental age of the individual and the social setting. Inappropriate responses may be both internalized  or externalized . Furthermore, evidence continues to emerge that deficits in more than one neurological pathway are responsible for emotional dysregulation in ADHD.situation selection , but as children grow older, they develop their own regulatory processes. Situation modification is an attempt, either extrinsically or intrinsically, to alter the subsequent course of the emotional response. Attention deployment is where the individual selects the aspect of the situation to focus on in order to help control the emotional response. Cognitive change is where the individual changes their perception of the situation (intrinsic), or they alter someone else’s perception, or have their own perception changed by someone else (extrinsic). Response modulation refers to the attempts to directly influence the response tendencies through the action of drugs, food, exercise and relaxation, etc. or by the modulation of emotion-expressive behavior. This process may not be learned at age appropriate times, and individuals with ADHD may have poor attention deployment and impulse control, thereby leading to premature exit from the cognitive process and resulting in emotional dysregulation.Figure Although caregivers and patients with ADHD constantly search for explanations for emotional lability such as that described in the two case examples at the beginning of this article, there is currently no gold standard for assessing emotional dysregulation in ADHD. In many cases, individuals with ADHD and significant impairment from emotional dysregulation do not meet DSM-5 criteria for a distinct co-morbid diagnosis. Having clinically useful measures of emotional dysregulation, and furnishing clinicians with a robust definition, could help caregivers and patients to improve their understanding of the condition. Defining and measuring emotional dysregulation on a clinical level should be a priority. Novel or new applications of neuropsychological instruments, neurophysiological and imaging techniques, and biomarkers of emotional dysregulation in children with ADHD are emerging, and however, more research is needed to develop reliable and universally accepted measures in affected children and to determine which deficits are particularly problematic at a functional level in terms of their daily life and social, emotional, and cognitive developmentOnce such measures are developed, they could be used to test the efficacy of potential treatments in emotional dysregulation. Clinically, parents report that there is improvement in emotional regulation when ADHD is treated pharmacologically, perhaps through improvements in the areas of impulse control and attentional deployment. ADHD pharmacotherapy does not, however, address the delayed development of cognitive control skills in individuals with ADHD. Hence, in addition to pharmacotherapy, treatment should focus on the learning of cognitive skills throughout the developmental process.


Bartonella koehlerae has been recently described as a new cat- and cat fleas-associated agent of culture-negative human endocarditis. It has been also encountered in one dog from Israel and six dogs from the USA, but other clinically relevant reports involving this bacterium are lacking.Bartonella koehlerae DNA in samples from blood and mitral valve tissue.A 7-year-old intact male mixed dog presented with clinico-pathological signs consistent with mitral endocarditis and cutaneous hemangiosarcoma. Molecular studies revealed the presence of B. koehlerae in Spain, corroborating that it can also be detected in dogs. Bartonella koehlerae infection should also be considered in Spain in humans and dogs presenting with clinical disease suggestive of it, such as culture-negative endocarditis.This is the first description of The online version of this article (doi:10.1186/s13071-017-2188-3) contains supplementary material, which is available to authorized users. Bartonella spp. are the etiological agents in humans and animals of several emergent and re-emergent vector-borne diseases that have a broad spectrum of clinical presentations including endocarditis, granulomatous diseases, meningoencephalitis, polyarthritis, uveitis or hemolytic anemia [c anemia .Bartonella koehlerae has been documented as a human pathogen and it has been increasingly detected in the last years [Bartonella koehlerae has been described in seven dogs from Israel and the USA with endocarditis, splenic disease, with suspicion of having a vector-transmitted infection or with hyperinsulinemic hypoglycemia syndrome [st years , 3. Thersyndrome –7.A case report of a dog with endocarditis is herein presented. Clinical investigation was performed and complemented with postmortem evaluation at Hospital Veterinario San Vicente . Techniques employed for laboratory workup were Procyte Dx Hematology Analyzer-Idexx, Catalyst Dx Chemistry Analyzer and IDEXX VetLab® UA™. Serologies were performed with rapid tests . Histopathology was performed at Histovet .Molecular investigation was initially performed at the SVGM  with EDTA-blood samples and freshly frozen tissue samples and further investigation was completed at the Intracellular Pathogens Research Laboratory . Samples shipped to the Intracellular Pathogens Research Laboratory consisted on DNA previously extracted at SVGM, EDTA-blood sample and paraffin-embedded tissue.Bartonella ITS region was performed by real-time PCR using oligonucleotides BsppITS325s: 5'-CTT CAG ATG ATG ATC CCA AGC CTT YTG GCG-3' and BsppITS543as: 5'-TAA AYT GGT GGG CCT GGG AGG ACT TG-3' as forward and reverse primers, respectively, to increase the sensitivity of the detection of a broader range of Bartonella species [B. henselae down to 0.001 pg/μl . qPCR was performed in an BioRad CFX96 Real-Time System, under the following conditions: a single hot-start cycle at 95 °C for 2 min followed by 55 cycles of denaturing at 94 °C for 10 s, annealing at 66 °C for 10 s, and extension at 72 °C for 15 s. Amplicons products were sequenced to establish species strain identification. The sensitivity of the qPCR assay is 98% at 0.001 pg/μl (0.5 bacteria genomes per μl).PCR screening of  species . AmplifiA 7-year-old intact male mixed dog was presented for a three-week history of anorexia, weight loss, polyuria and polydipsia that had worsened to severe generalized weakness at presentation time. There was also a cutaneous mass located in the right flank that had ruptured some days before resulting in serosanguinolent discharge. The dog lived outdoors, was regularly vaccinated and dewormed. Physical examination abnormalities included poor body condition , fever (40 °C), tachycardia, grade 3-heart apex systolic murmur, pain in several joints, abdominal discomfort and an ulcerated cutaneous mass in the abdomen.Leishmania and SNAP 4Dx  serologies were negative.Laboratory workup revealed left shift leukocytosis , neutrophilia , thrombocytopenia , azotemia , increased ALP , hypoalbuminemia , low USG (1.020) and proteinuria . Microbiologic urine and blood cultures, and Abdominal ultrasound evidenced generalized splenomegaly and diffuse nodular hypoechoic peripheral lesions in both kidneys. Thorax radiographs showed an alveolar pattern on right lung lobes and left cranial lung lobes. Thickened mitral valve with regurgitation was detected on echocardiography. Fine needle aspiration of the cutaneous mass and spleen were consistent with a mesenchymal neoplasm and reactive splenomegaly, respectively.Intensive treatment for presumptive infective endocarditis and septic shock was performed with fluid therapy, antibiotics (ampicillin and enrofloxacin), ranitidine and low molecular weight heparin. However health status deteriorated rapidly and the dog died twelve hours after admission. Necropsy confirmed mitral endocarditis Figs. , 2, 3 anBartonella as previously described [Bartonella/alpha-Proteobacteria growth medium (BAPGM) pre-enrichment blood culture [Bartonella spp. The presence of Bartonella koehlerae DNA was confirmed in blood , and in tissue   targeting a fragment of the 16S-23S ribosomal RNA intergenic spacer (ITS) was performed on extracted whole blood and mitral valve tissue  at the SVGM using conserved primers for species of the genus escribed , which y culture  and fromBartonella koehlerae in Spain, as the causative agent of Bartonella endocarditis involving the mitral valve in a dog.Here, we report the first description of Bartonella infection at the time of blood collection. Previous research has emphasized that negative blood cultures are especially frequent in Bartonella-induced endocarditis and other techniques are needed for diagnosis [Bartonella species [B. vinsonii berkhoffii is one of the most common agents found in canine Bartonella endocarditis, where infection often involves the aortic valve [B. koehlerae and B. henselae, have been recently implicated in canine endocarditis in the USA and Israel [Bartonella spp. has been reported in people in the past ten years and the number of cases is likely to be underestimated [Infective endocarditis is an uncommon and often deadly disease in dogs that represents a diagnostic challenge in most of the cases because echocardiogram can be normal, and blood cultures can yield false-negative results due to the low-grade and intermittent bacteremia associated to iagnosis . The com species . Previouic valve . Howeverd Israel , 11. In stimated .Bartonella spp. should be investigated as a cause of vasoproliferative tumors in both humans and dogs, due to their ability of enhancing endothelial cell proliferation in conjunction with inhibition of apoptosis [Bartonella involved are B. bacilliformis, B. quintana, B. henselae, B. vinsonii berkhoffi and B. koehlerae. Unfortunately, definitive association of Bartonella and the skin hemangiosarcoma could not be established in this study since Bartonella DNA could not be amplified from the skin tumor. False-negative PCR results could be caused by prolonged period of formalin fixation [Bartonella as cofactor in the development of cancer [Interestingly, recent reports suggest that poptosis , 14. Spefixation , 16. Furf cancer , 14.Bartonella infection is present in people in the Valencian Community and Catalonia (Spain) [In Spanish dogs, presence of canine bartonellosis has been demonstrated with serological studies . Moreove (Spain) , 20.Bartonella spp. in dogs may prove to be a legitimate medical concern, as dogs have been also implicated in the transmission of bartonellosis following a bite or a scratch [Bartonella koehlerae has been described as a cat-associated agent of culture-negative human endocarditis [Definitive documentation of the causative  scratch , 22. Barcarditis , and thiBartonella organisms as sand flies, human body lice, cat fleas, ear mites, and ticks have been described as potential vectors [Bartonella spp. may be more substantial than is currently believed and, until an effective vaccine in the protection against Bartonella spp. could be available, ectoparasites control measures should be implemented in both dogs and cats to avoid the potential of zoonotic transmission of this severe infection to humans.The findings presented in this manuscript reinforce the concept of “One Health” approach, which requires close communication in all aspects of health care for humans and animals, with the aim of supporting public health in general. It is worth highlighting that there are many vectors that could harbor  vectors . TherefoBartonella koehlerae in Spain, corroborating that the parasite can also be detected in dogs. Bartonella spp. infection should also be considered in Spain in humans and dogs presenting with features suggestive of it, such as blood culture-negative endocarditis.To our knowledge, this is the first description of


To validate the association between country-of-birth and disparities in the stimulant use for ADHD among individuals in Western Australia.Using linked data, a population-based retrospective cohort of individuals admitted to hospital before age 25 years was followed through to identify having stimulants for ADHD in 2003–2007. Multivariate logistic and linear regressions were used to characterise associations between stimulants and country-of-birth, geographical remoteness and socioeconomic status.Of 679,645 individuals, 14,122 (2.1%) had a record of having stimulants for ADHD. Of these, 205 (1.5%) were born in Africa, Asia, Middle-East or South America, while 13,664 (96.8%) were born in Australia/New Zealand, Europe or North America. Individuals with traditionally non-Anglophonic backgrounds were around one-half as likely to have stimulants as individuals with Anglophonic backgrounds . Non-Anglophones were an average of 2.7 years older than Anglophones at onset of having stimulants. Individuals from remote and disadvantaged backgrounds had stimulants at younger ages than individuals living in metropolitan areas and with least disadvantage.The results highlight the importance of identifying factors underlying cultural differences in stimulant treatment for ADHD. Improving awareness of cultural variations may foster trust and rapport between patients and clinicians, and so better facilitate the appropriate and effective treatment of ADHD for each patient. Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed chronic neurodevelopmental disorder in children and adolescents . PsychosWe conducted a population-based retrospective cohort study using the WA Data Linkage System and linked three state-wide statutory health databases: the Hospital Morbidity Data Collection (HMDC) for inpatient separation, Monitoring of Drugs of Dependence System (MODDS) for stimulant records, and the Deaths Register . The WA The HMDC is a core dataset routinely linked by the WA Data Linkage Branch to other administrative health data and is one of the largest data collections managed by the WA Department of Health (WADoH) . In 2012WA is a state occupying the western third of the Australian continent with an estimated population of 2.5 million, around 11% of the national total in 2013 . It was Geographical remoteness was scored according to the Accessibility/Remoteness Index of Australia of the Australian Census, using whichever of the 1996, 2001 or 2006 indices were closest to the year of cohort entry, and was grouped into three levels: metropolitan, rural and remote . The indIndividuals’ countries of birth were grouped under eight major geographical regions of the world according to eHRAF  databaseThe outcome measure was at least one prescription stimulant for ADHD dispensed during 2003–2007. Descriptive statistics were performed for all study variables, including means and standard deviations obtained for continuous variables, and frequencies and percentages for categorical variables. Univariate and multivariate logistic regression models were used to examine factors associated with stimulant use. Individuals’ age for initial prescription stimulants between 2003 and 2007 were compared using multiple linear regression. Missing values where information was unknown for each variable were treated as a separate ‘unknown’ exposure category so that all subjects were included in the analyses. Individuals who died prior to 2003 were excluded from the study sample. Individuals identified themselves as Aboriginals were also excluded from the analysis. This exclusion followed the methods employed in a previous study due to likely cultural differences in the understanding of ADHD and attitudes towards medication between Aboriginals and non-Aboriginals .Of the 679,645 individuals admitted to hospital for the first time by the age 25 years, 14,122 (2.1%) received a prescription stimulant for ADHD treatment during 2003–2007. The characteristics of the cohort are shown in Table Both univariate and multivariate models indicated that individuals with LPNO backgrounds were approximately half as likely to receive stimulants compared with those with HPNO backgrounds  Table . FemalesThe mean age at onset of stimulants for those with a LPNO background was nearly three years older than in those with a HPNO background  Table . Males rOur study found that prescription stimulants in WA varied significantly according to an individual’s country of birth. In particular, the odds of having stimulants in those born in Africa, Asia, Middle-East or South America were around one-half, and the mean age was 2.7 years older than in those born in Australia, Europe or North America. These findings are consistent with those documented in the earlier Ghosh et al.  study whThere were several limitations of the method used in this study. First, the individual’s country of birth variable was used as a surrogate given the absence of more direct ethnicity information. Groupings based on country of birth limited the capacity to detect differences between ethnicities and regional variations within countries to some extent, although it is generally agreed that country of birth plays a role in influencing individuals’ beliefs and attitudes. Second, detailed immigration information was unavailable and, therefore, we could not evaluate the association between stimulant use and refugee status or skilled migration. Third, our datasets did not allow us to identify anyone diagnosed with ADHD, yet not treated with stimulants. Fourth, as the stimulant data were only available from 2003, starting from initiation of the Stimulant Regulatory Scheme in WA, the first record in the stimulant dataset might not have been the first stimulant record in an individual’s life. In the absence of information prior to 2003, we were unable to observe the duration of stimulant treatment or dose information and, therefore, possible progression of ADHD symptoms in an individual’s life. Findings were further limited by the fact that records of dispensed prescription stimulant may not always determine the actual pattern of stimulant use for ADHD treatment, especially because there is a high prevalence of diversion and misuse of pharmaceutical stimulants among the adolescent and young adult student populations with ADHD . NeverthThe strengths of this study compared with previous published studies were the use of whole-population linked data on a study population of nearly 700,000; a study cohort representing approximately 40% of the WA population aged 0–25 years between 1980 and 2007; and use of a comparison group of people with no records of stimulant use for ADHD. Whilst the representativeness of our cohort and the purity of exposure contract were far from perfect, they were superior to what can be achieved in a clinic-based research setting where subjects are typically highly selected and their treatments obtained outside unreliably recorded.Cultural attitude towards ADHD behaviour, and resistance to accept a biomedical cause of ADHD and medication treatment are the prime reasons for a reduced likelihood of prescription stimulant and delayed onset of stimulant use among LPNO groups. Individuals’ perceptions of normal and pathological behaviour are largely determined by cultural beliefs which influence their care-seeking behaviour . For exaLower rates of medication treatment and delay in treatment were documented among Latino adolescents and youth in Venezuela largely due to a reluctance to accept medication treatment . ResearcOur findings also revealed that males were 69% more likely to receive stimulant than females possibly due to gender variation in ADHD manifestations, where boys exhibit more hyperactivity than girls, who display mostly inattentiveness . As ADHDWe found individuals living in the metropolitan areas were more likely to have prescription stimulants. Studies have examined differential healthcare access, availability of physicians and ready access to healthcare services in major cities as factors influencing regional variation in stimulant treatment . DiffereUsing a different method, this study validated cultural differences in stimulant treatment for ADHD reported in previous research, and identified significant country of birth variations, as well as gender, regional and socioeconomic disparities in stimulant use for ADHD in WA. Individuals born in Africa, Asia, Middle-East or South-America were less likely to have stimulant treatment than individuals born in Australia/New Zealand, Europe or North America. A greater likelihood of stimulant treatment among boys, individuals living in metropolitan areas, and living with socioeconomic disadvantage was also observed. The findings highlight the need for tailoring ADHD diagnosis, treatments and service delivery appropriately to children and adolescents from diverse cultures.


Two models of attention deficit hyperactivity disorder (ADHD) coexist: the biomedical and the psychosocial. We identified in nine French newspapers 159 articles giving facts and opinions about ADHD from 1995 to 2015. We classified them according to the model they mainly supported and on the basis of what argument. Two thirds (104/159) mainly supported the biomedical model. The others either defended the psychodynamic understanding of ADHD or voiced both models. Neurological dysfunctions and genetic risk factors were mentioned in support of the biomedical model in only 26 and eight articles, respectively. These biological arguments were less frequent in the most recent years. There were fewer articles mentioning medication other than asserting that medication must be combined with psychosocial interventions (14 versus 57 articles). Only 11/159 articles claimed that medication protects from school failure. These results were compared to those of our two previous studies. Thus, both French newspapers and the specialized press read by social workers mainly defended either the psychodynamic understanding of ADHD or a nuanced version of the biomedical model. In contrast, most French TV programmes described ADHD as an inherited neurological disease whose consequences on school failure can be counteracted by a very effective medication. Mass media have widely discussed attention deficit hyperactivity disorder (ADHD) and have contributed to shape its perception by the public , three weekly newspapers  and two major regional dailies (Le Progrès and Sud Ouest). We selected national journals on the basis of their circulation ranking, after exclusion of specialized journals such as L’Equipe (sport), Les Echos (economy) or TV Magazine (TV programmes). We selected two regional dailies that widely differ regarding their distribution area. We used the EUROPRESSE database (www.europresse.com) to collect all articles published from January 1995 to December 2015 in these nine newspapers and containing the keyword “hyperactivity/hyperactive”. We used this keyword rather than the French translation of ADHD (TDAH) because it is much less common in the French media than “hyperactivity”. We identified 709 articles and, then, excluded: (i) articles where the term “hyperactivity” is used to describe the behaviour of normal people (e.g. hyperactivity of a politician); (ii) articles where hyperactivity is only associated with another disease (e.g. hyperactivity in children with autism); and (iii) articles that marginally mentioned ADHD and provided no information or opinion about it. We kept 159 articles dealing with “hyperactivity” considered as a disorder or, at least, a symptom. The list is available on request to the first author.We collected press articles dealing with ADHD in four major French national daily newspapers (We classified each article into three categories: (i) those that mainly support the biomedical model of ADHD; (ii) those that mainly defend the psychodynamic understanding; and (iii) those that voice both views. We also analysed the discourse about ADHD through five detailed questions that may or may not be discussed in each article. The first one is related to the contribution of genetic factors to ADHD etiology. We classified articles reporting on this question as (i) defending that genetic factors are the main contributors; (ii) defending that environmental rather than genetic factors play a major role; and (iii) giving voice to experts defending both views. The second question is related to the causes of ADHD beside genetic factors. We considered four classes of causes: (i) neurological or neurodevelopmental dysfunctions; (ii) premature birth; (iii) inappropriate education (either provided by parents or school); and (iv) other causes . The third question is related to ADHD treatment: when an article tackles this question does it favour medication, psychotherapy or a combined treatment? The fourth question is related to the effectiveness of medication to decrease the risk of academic underachievement. The fifth question concerns articles discussing the use of brain imaging to diagnose ADHD. We identified in each article whether or not it discussed these five questions. Therefore, for each article we filled a reading table of 23 items. This reading table was first coded by one author (FG) and then independently coded by the other author (SP). The few disagreements were resolved by discussion. The reading table of the 159 articles is given in supplementary material (Ponnou-data.xlsx). All articles were written by journalists. They often gave voice to health professionals  and to parents, either as short quotations or full interviews, but not to children. However, we did not quantify these quotations in the present study.Among the 159 articles we found only 55 explicitly defending the psychodynamic model, either alone (26 articles) or voicing both models (29 articles). About two-thirds of articles were classified as mainly supporting the biomedical model. This percentage was remarkably stable over two decades .Table I.Le Monde, 16 November 2009)The contribution of genetic factors to ADHD is likely strong, according to experts. Studies suggest that the heritability of ADHD might range between 60% and 80%. This means that an ADHD patient might have a 60 to 80% chance of inheriting it through genes. : “It is obvious that hyperactive children suffering from attention deficit are increasingly numerous. One cannot put forward genetic mutations. Therefore, we must wonder about societal changes.” Twelve articles voiced both opinions. Of the eight articles supporting a major genetic causation for ADHD, only one echoed a scientific study. On 2 October 2010, the most respected French newspaper Le Monde echoed a study published in the prestigious medical journal The Lancet and claiming that DNA deletions or duplications are twice as frequent in ADHD children as in unaffected ones  ADHD is said to be: “an immature neurological functioning in the frontal area [of the brain], that is supposed to control impulsivity”. Only one article published in 2009 discussed these possible dysfunctions and challenged this conclusion on the basis of scientific arguments: differences observed with brain imaging techniques between ADHD children and controls are mild, often inconsistent between studies and do not prove that they are the cause rather than the consequence of the disorder . This representation of ADHD as resulting from neurological dysfunctions reached its maximal frequency during an early period (2001–2005) and then declined in absolute number .Among the 159 articles examined, 26 represented ADHD as caused by neurological dysfunctions. For example in the e number  and evene number . MoreoveLa Croix (25 May 2011) put: “A Swedish study published in the journal Pediatrics highlights that premature birth is linked to the risk of receiving an ADHD treatment some years later.” It must be noted, however, that prematurity is not a major concern in France: the rate of premature birth is much lower (5.8%) than in the USA (12.7%) Since the late 1990s psychiatrists have made up a new disorder to describe children who are disruptive at school: attention deficit hyperactivity disorder. And, then, they have diagnosed children who present symptoms of inattention such as squirming in their seats, moving their feet or challenging all forms of authority. In other words they have transformed into a mental disorder, and then into a world-wide epidemic, what was nothing but a disturbance linked to difficult relationships between children, parents, educators and teachers. Canadian scientists … have performed a prospective study on 4874 children who lived with both their parents in 1994. They then compared the rate of psychostimulant prescription in 2000 between children still living with their two parents and children whose parents had divorced. The results showed that 6.1% of the children whose parents had divorced were on medication whereas only 3.3% of those living with the parental couple were.  reported: “Several scientifically sound studies have demonstrated that excessive exposure to screens [TV or video games] is linked to attention deficit.” Four articles highlighted the possible risk linked to the excessive consumption of certain food , but another article, in agreement with short-term studies  stated about ADHD: “A diagnosis of ADHD justifies a methylphenidate prescription.” Eighteen articles cited various alternative options only . The vast majority Methylphenidate, the only drug authorized [in France] to treat ADHD, has been put at its rightful place: never as first-line therapy, always in combination with therapies and only if the child and his/her parents are in real need of it to silence symptoms until the troubles ease. The effects of this drug [methylphenidate] are worrying and the future of medicated children reaching adulthood is unknown. On medication, growth is slowed down, heart rate and blood pressure are increased, and psychotic symptoms may occur. In France and other European countries cases of abuse and addiction are documented. This prescription should be the last resort for treating only the most severe cases. . In the early period (1995–2000) 60% of the articles expressed the fear that this medication might have unknown long-term side effects and might be diverted and abused. Most articles also emphasized that psychostimulant medications are overprescribed in the USA and quoted experts that warned against over-prescription in France. After this early period, these criticisms were less frequent but did not disappear . These cThe number of articles questioning medication is also given in % of the total number of articles in the same period see .Academic underachievement was frequently cited as the inescapable consequence of untreated ADHD  and thisL’Express (29 March 2004) reported: “Studies about the long-term outcomes of methylphenidate treatment show no benefit regarding academic underachievement and social integration compared to untreated ADHD sufferers.” In contrast, among the 11 articles suggesting that medication is protective, six reported only on individual cases of ADHD children that improved their school performances after starting medication. A typical example from La Croix (7 May 2013) illustrates this rhetoric: “Julien, who for long was not able to benefit from a standard school, is now medicated. With the drug this 10-years old boy is able to concentrate, to keep up at school and regains his self-confidence.” The five remaining articles put this type of assertion: “Medication can prevent school exclusion and the fall of school performances” .While French press articles frequently mentioned school failure as a major concern for ADHD children (59 articles), only 11 of these articles explicitly suggested that medication can protect children from this risk . In addiLe Progrès, 26 November 2002) suggested that brain imaging is able to detect differences between ADHD children and controls. According to this article, brain metabolism is increased in the frontal region of ADHD children. It is likely that this article echoed a study published in November 1990 in The New England Journal of Medicine claiming that glucose metabolism is depressed in the frontal region of ADHD adults. Indeed, this study has been widely covered by US newspapers, while the subsequent studies that disconfirmed this initial claim did not attract newspapers’ attention . The remaining 156 articles we examined did not mention brain imaging.Only one article . However, the percentage of articles exclusively supporting the psychodynamic understanding of ADHD is low and does not depend on the political orientation (According to reports from the French Institute of Public Opinion (IFOP) the nine journals we examined were distributed in three groups according to their main political orientation: HD model . We obseentation . In thisSocial studies about ADHD often express the opinion that the pharmaceutical industry strongly contributes to creating and extending the market for ADHD drugs . Its president since 2002 is very active. She has been cited by 15 articles of our corpus and defends a nuanced view of the biomedical model that acknowledges the complexity of ADHD etiology  of French newspaper articles actually supported the biomedical model.In line with this, several experts defending the biomedical model nevertheless emphasized that ADHD is a real disorder but not a disease. Neurological dysfunctions are put forward in only 26 articles and genetic factors are said to play a major role in only eight articles. Taking into account that five articles highlighted both alleged biological causes, only 29 articles out of the 133 articles classified as defending either the biomedical model alone, or both models, put forward biological arguments in support of the biomedical model. Moreover, these alleged neurogenetic arguments were less frequent in the recent period (2011–2015). Thus, according to most French newspapers, ADHD is a real syndrome that may require medication in combination with other therapeutic approaches, but not a neurological disease that can be treated by a drug.Studies investigating ADHD representation in US and Swedish newspapers during the 1990s concluded that the general press favours the biomedical model  rather than on the society and this might reflect the influence of psychoanalysis in France. In line with our observation, Horton-Salway , p. 533,Considered as a whole, the discourses about ADHD in the French general press and in the specialized press directed at social workers were similar in several aspects. First, a small minority of articles put forward neurological and/or genetic arguments in support of the biomedical model. Second, a few articles asserted that medication protects ADHD children from school underachievement. Third, both discourses remained almost silent about the role of major social factors such as poverty, school policies and the influence of the pharmaceutical industry. However, the psychodynamic understanding of ADHD dominated in the specialized press (56%) whereas it did not in the general press (35%) (Ponnou et al., In contrast, the discourse about ADHD in French TV programmes widely differed from that of the general and specialized press. First, 16 out of 60 French TV programmes discussed the contribution of genetic factors to ADHD and 11 of them claimed that ADHD is a genetic disease without giving voice to opposite opinions (Bourdaa et al., One major limitation of our studies is that we did not investigate the role of the Internet, although it does play a role, at least through the website maintained by the TDAH-France association (Edwards et al., The biomedical model of ADHD exclusively focuses on the biology of the patient and promotes medication as the most appropriate treatment. French TV programmes mainly defended this strict biomedical model. In contrast, the French press, either general or specialized, mainly defended a more complex understanding of ADHD etiology and treatment. Even medical experts supportive of ADHD medication mainly defended in the press, but not in TV programmes, a nuanced opinion about ADHD: the familial and social contexts must be taken into account, medication can help but in combination with educative and therapeutic approaches. Unfortunately, surveys show that TV programmes represent the main source of information about health for Europeans (European Commission, One might also wonder what medical doctors who defended a nuanced view of the biomedical model in newspapers, but a strictly biological one on TV, actually say to parents. In France the prescription of methylphenidate is constrained: the first prescription, and its renewal each year, must be done by a psychiatrist in a public hospital. We have heard that prescription practices widely vary between hospitals. This may suggest that the discourse to parents that is put forward to justify medication, or its absence, also widely varies and this might deserve investigation.Click here for additional data file.