A discourse analysis was performed based on an online document under the headline: “What is Attention Deficit Hyperactivity Disorder ?” published by the National Institute of Mental Health (NIMH), USA. Three parts of the document were analysed: (1) The introductory part, as this sets the tone of the whole text. (2) Parts of the text that were specifically addressed to parents. (3) Etiology and pathology of “ADHD” with reference to a number of different symptoms and behaviors. Inattention and hyperactivity are presented in the document as a floating spectrum of symptoms caused by “ADHD.” Other factors of importance for children's development, that is, early attachment, close relationships, previous experiences, culture, and contexts are ignored. Children who are perceived as inattentive and hyperactive are portrayed as having inherent difficulties with no reference to their emotions or efforts to communicate. The child is viewed as suffering from a lifelong disorder that might not be cured but controlled by a diagnosis and subsequent medication. Parents are advised to control their child's behavior and to strive for early diagnosis in order to receive treatment provided by experts. Those who are presented as experts rely on a biomedical model, and in the document, detailed descriptions of medication to correct the undesired behaviors are provided. The value of judgment in the assessment of different symptoms and behaviors that signifies “ADHD” is absent, rather taken-for-granted beliefs were identified throughout the document. A heterogeneous set of behaviors is solely described as a disorder and hereafter it is stressed that the same behaviors are caused by the disorder. In this manner, cause and effects of “ADHD” are intertwined through circular argumentation. In the Western, industrialized world, there is an ongoing process of individualization in which behaviors, life course, and experiences of human beings increasingly are understood at the level of the individual, whereas the influence of institutions, economy, class, and social crises are underestimated  is a paramount example of how human suffering increasingly is viewed as a psychiatric disorder. Freedman  in a disCo-occurring difficulties tend to be depicted as caused by “ADHD,” even though there might be underlying difficulties that lead to symptoms of “ADHD” as well as to other difficulties  present officially on their website. As parents are influenced by discourses on “ADHD” and are also involved in interventions when a child receives a diagnosis, our priority goal was to examine how “ADHD” and children perceived as having “ADHD” are described, and how the information was used to provide advice to parents. More specifically, the main goal was to identify, by the use of a discourse analytical approach, naturalized and taken-for-granted assumptions. Influenced by Jörgensen and Phillips , we formconstructed as the building up of words, categories, and repertoires, and so on, which portrays a special version of the world. But it is also constructive because using the words, categories and such produces the perceived world. The second principle implies that discourse is action-oriented, meaning that we are acting out within a social arena when writing or talking. The third principle acknowledges that a discourse is always situated; words or writings are situated as it takes place in an institutional setting or within a “particular argumentative framework” ?” published by National Institute of Mental Health (USA). It was gathered from the website of the institute; www.nimh.nih.gov/health/publications/attention-deficit-hyperactivity-disorder/index.shtml and downloaded on October 25, 2015. Three parts of the text were selected for the discourse analysis. (1) The introductory part, as this sets the tone of the whole text and was considered important for the comprehension of the remaining parts. (2) Those parts of the text that were specifically addressed to parents. (3) Etiology and pathology of “ADHD” with reference to a number of different symptoms and behaviors.Discourse analytical steps. As pointed out by Yardley ( Yardley , languagEthical considerations. When adopting a discourse analytical approach, the researcher's responsibility also implies to be sensitive to those ethical issues that need to be considered in the investigation. Both questions that are raised to the text and the text itself must be evaluated from an ethical frame of reference. Discursive analysis is a technical and analytical activity rather than a way to provide understanding of individuals and their subjective experiences. Since the method, by definition, implies that arguments are decomposed, problematized, and even questioned, the method should be used with caution when studying individuals who, in any way, are disadvantaged or marginalized. There is a risk that we as researchers place ourselves in a superior position by making use of the individuals’ narratives not telling them that their talk is going to be decomposed and scrutinized. An alternative purpose of discursive methods is however to analyse how communities of, for example, researchers and professional organizations use language on a “macro level” (Seymour-Smith, It is not clearly stated in the first part of the document to whom the information on “ADHD” is provided. Further down, it appears that the information concerns both parents that suspect that their children are suffering from “ADHD” as well as parents whose children already have received a diagnosis. In this way, parents who perceive their child as inattentive and/or hyperactive become directed toward “ADHD” as an explanation for the perceived problematic behaviors of the child. Thereby, the focus is pointed in the direction of “ADHD” as the most likely answer to the parents’ worries and questions.Although “ADHD” is characterized as a floating spectrum of symptoms, it is transformed into a distinct entity that appears clearly defined solely by its name. While it is difficult to define the dividing line between normal and abnormal, the label “ADHD” appears sharp and exact and explanatory in itself. The use of the word “severe” makes the reader observe characteristic differences between the normal and the abnormal child. The definition of abnormal behaviors is, however, a result of social decision-making, and a sharp line between normal and abnormal behaviors is illusory as pointed out by Börjesson  and WintAn image of “ADHD” as a legitimate medical disorder is established by the first sentence: “ADHD is one of the most common childhood disorders.” The repeated use of the term “disorder” together with a number of references to brain imaging and brain chemicals creates an impression of a chronic and long-term disability. A detailed and clearly defined description of “ADHD” seems nevertheless hard to concretize. The subtle language reveals the incompleteness of the medical discourse: “To be diagnosed with the disorder, a child must have symptoms for 6 or more months and to a degree that is greater than other children of the same age.” Since social and relational aspects of children's behaviors, emotions, and reactions are toned-down, the reader gets the impression that the described difficulties are causal consequences of “ADHD.” Nothing is mentioned about circumstances within the family that might lead to the child being “out of control”: “Parents may first notice that their child loses interest in things sooner than other children, or seems constantly ‘out of control’.” “Often, teachers notice the symptoms first, when a child has trouble following rules, or frequently ‘spaces out’ in the classroom or on the playground.” No remarks in the text, or references, are to be found concerning the organization of the school in order to understand why the child has troubles following rules or “spaces out.” Alternative discourses are thus excluded. It is stated in the document that “ADHD can be mistaken for other problems.” It is further stated that: “For example, adults may think that children with the hyperactive and impulsive symptoms just have disciplinary problems.”The discourse of causation leaves no room to question the legitimacy of “ADHD” and so the reader is assured that “ADHD” has a biomedical origin. More specifically, explanations to behaviors such as inattentiveness, hyperactivity, and impulsivity are delayed maturation of the child's brain: “Brain imaging studies have revealed that, in youth with ADHD, the brain matures in a normal pattern but is delayed, on average, by about 3 years. The delay is most pronounced in brain regions involved in thinking, paying attention, and planning. More recent studies have found that the outermost layer of the brain, the cortex, shows delayed maturation overall, and a brain structure important for proper communications between the two halves of the brain shows an abnormal growth pattern. These delays and abnormalities may underlie the hallmark symptoms of ADHD and help to explain how the disorder may develop.” Presumably, after this declaration, some parents get the impression that “ADHD” is a diagnosis with objective criteria. A critical reader however would question why a delay in maturity becomes equivalent with a disorder. In addition, average group differences concerning “ADHD” or any other condition say little about the unique individual Falkum, .In fact, as shown in the document, there are no biological markers, environmentally defined categories, or objective tests to distinguish “ADHD” as a discrete condition. Rather, diagnostic criteria are subjectively interpreted from the behavior of the child: “No single test can diagnose a child having ADHD. Instead, a licensed health professional needs to gather information about the child, and his or her behavior and environment.” Professionals as well as teachers and parents are involved in the evaluation and examination process, and subsequently in the diagnostic process. Rafalovich  as well Although the expected behavior of being “out of control” is absent, the child might nevertheless meet the criteria for a diagnosis, as exemplified here: “They may sit quietly, but they are not paying attention to what they are doing. Therefore, the child may be overlooked, and parents and teachers may not notice that he or she has ADHD.” The criteria of inattention thus seem hegemonic. Since inattention is a considerably varying concept, according to the document it concerns both being easily bored and switching from one activity to the other and moving slowly, “ADHD” is a subject that varies considerably. Both the child with hyperactive behaviors and the child who is “quiet and well-behaved” are candidates for an “ADHD” diagnosis. There is thus a circular argument in that ADHD is defined according to the presence of particular behaviors which the diagnosis is then proposed to explain. Furthermore, the behaviors associated with ADHD seem hard to define: “Children mature at different rates and have different personalities, temperaments, and energy levels. Most children get distracted, act impulsively, and struggle to concentrate at one time or another. Sometimes, these normal factors may be mistaken for ADHD. ADHD symptoms usually appear early in life, often between the ages of 3 and 6, and because symptoms vary from person to person, the disorder can be hard to diagnose.”The idea that children suffer from inherent medical disorders diverts attention away from problems that are contextual, such as, for example, problems within the school or within families. Bad feelings in parents are exemplified as stemming from the child's problems and not from family dynamics or other contextual reasons. Parents are comforted by the assumption that they need education about “ADHD” and help to handle negative feelings: “Before a child is diagnosed, frustration, blame, and anger may have built up within a family. Parents and children may need special help to overcome bad feelings. Mental health professionals can educate parents about ADHD and how it impacts a family.” The reader is taught that if the child receives special help, bad feelings caused by “ADHD” can be overcome. In the NIHM document, bad feelings in parents are depicted as a result of the child's inherent inattention and hyperactivity. It is reasonable to assume that parents feel bad if their children have difficulties. However, such feelings might as well be reactions that arise between individuals who are closely related to each other according to Clarke et al.  and CritNo observable strengths and positive characteristics in the child are mentioned in the document. When an alternative explanation is raised, it still concerns the inner state of the child indicating signs of psychiatric disorder: “Has anxiety or depression, or other psychiatric problems that might cause ADHD-like symptoms.” Although researchers (e.g., Saul, In the document, those who advocate the biomedical discourse are portrayed as experts who have the “correct” knowledge about “ADHD” and hold the power to choose a proper language whenever this label is introduced to the lay public or elsewhere. In their role as experts, they should explain how children with “ADHD” could be best understood and helped. A reference, attached to the document, gives the impression that there are strong reasons to believe that parts of the brain are involved in the pathogenesis of the disorder. “A study of children with ADHD found that those who carry a particular version of a certain gene have thinner brain tissue in the areas of the brain associated with attention. This research showed that the difference was not permanent, however, and as children with this gene grew up, the brain developed to a normal level of thickness. Their ADHD symptoms also improved.”The biomedical model is portrayed as the evident paradigm, since about a third of the document concerns medication. Professionals who do not adhere to the biomedical model thus implicitly become positioned as unable to help children with “ADHD.” “With treatment, most people with ADHD can be successful in school and lead productive lives. Researchers are developing more effective treatments and interventions, and using new tools such as brain imaging, to better understand ADHD and to find more effective ways to treat and prevent it.” Alternative discourses that acknowledge other understandings and solutions to the children's difficulties are thus excluded. It is assumed that expert professionals are willing to assist children who meet the criteria for an “ADHD” diagnosis. Children perceived to have ADHD need to be evaluated in order to determine whether they qualify for special education services. “Once your child has been evaluated, he or she has several options, depending on the specific needs. If special education services are needed and your child is eligible under the Individuals with Disabilities Education Act, the school district must develop an ‘individualized education program’ specifically for your child within 30 days.” An early identification is stressed to be crucial. “Recognizing ADHD symptoms and seeking help early will lead to better outcomes for both affected children and their families.” The outcome and the future for afflicted children who do not receive help at an early stage are, as this sentence illustrates, not so promising. “These symptoms can make it difficult for a child with ADHD to succeed in school, get along with other children or adults, or finish tasks at home.”The biomedical discourse assumes that there is a consensus among professionals on how to interpret the behaviors of the child, which means that pharmacological treatment is the preferred intervention. Graham et al.  describeNon-medical treatments, such as behavioral training and educational interventions, are discussed briefly after a lengthy description of brands of medication that are available for the afflicted child; “Behavioral therapy aims to help a child change his or her behavior. It might involve practical assistance, such as help organizing tasks or completing schoolwork, or working through emotionally difficult events.” Three pages of the document are devoted to describing medical treatments, a half page is devoted to describing psychotherapy, and one and a half page is devoted to giving advice to parents.Information and advice given to parents are typically presented as aiming at controlling and changing the child's behaviors: “If your teen breaks rules, your response should be as calm and matter-of-fact as possible. Punishment should be used only rarely. Teens with ADHD often have trouble controlling their impulsivity and tempers can flare. Sometimes, a short time-out can be calming.” The categorization of children assumed to suffer from “ADHD” leads to generalizations. Through the diagnosis, the child is distinguished from other children and may incorporate a new identity, shaped by the characteristics of “ADHD.” Hence, the diagnosis functions as a filter through which individuals understand their difficulties, emotions, and themselves, a process that has been described by Brinkmann . It is aThe diagnosis is portrayed as a relief for the children as well as for adults who receive a diagnosis later in life since this ought to provide them with an explanation for their difficulties and in turn allow them to handle their problems more effectively. As it is put forward that children should be diagnosed as early as possible, a good parent is a parent who understands that they should help their child to receive a diagnosis in order to prevent future problems. “For some adults, a diagnosis of ADHD can bring a sense of relief. Adults who have had the disorder since childhood, but who have not been diagnosed, may have developed negative feelings about themselves over the years. Receiving a diagnosis allows them to understand the reasons for their problems, and treatment will allow them to deal with their problems more effectively.” Personal advantages for the parents are that they will have an explanation for the child's difficulties.Although behavioral training and educational interventions are mentioned in the NIMH document, the inventors are categorizing “ADHD” as a biomedical disorder with medication as the first-choice treatment. Phenomena such as dysfunctional relationships between parents as well as stress and illness in the family can lead to inconsistent and/or insensitive parenting which in turn can result in hypervigilance, fast responses, and inability to regulate emotions (Crittenden & Kulbotten, In the document, there are no attempts to scrutinize any aspect of the “ADHD” diagnosis. Questions that could be raised are: Who and what made the children feel like failures in the first place? How can acceptance of a dysfunction be associated with a more positive development? Seen from the viewpoint of a psychosocial discourse, a diagnosis can be perceived as transporting blame to the child presuming that the child is living in a vacuum. Diagnoses currently are depicted as beneficial since they counteract stigma connected to mental distress. At the same time, according to Timimi , medicalA discourse is repeatedly constructed by the exclusion of other possible interpretations that belong to the field of discursivity, a term originated from Laclau and Mouffe's  discoursIn searching for the prevalence of discourses in the field of “ADHD,” it became clear that the biomedical discourse dominated, and under its wings has made room for a conglomerate of different medical and pharmacological research branches. The discursive method enabled us to entail a critical approach to “taken-for-granted knowledge” maintained by this dominant discourse. The discursive method also made it possible to raise crucial questions with reference to the agenda of the NIMH's information to parents who needed guidance for being able to carry on their role as parents. Validity in discourse analysis can be determined by the examination of coherence in what has been presented. To establish validity, it must be evident that different aspects of the analysis are in line with the discourse (Potter & Wetherell, There has been an escalation of biomedical understanding of children's behavioral and emotional problems and a subsequent increase of drug prescriptions for such behaviors (e.g., Polanczyk et al., It is possible that children identify with and even become attached to their diagnosis, as they in their daily interactions are encouraged to inform other people about the diagnosis. Individuals can, for various reasons, take advantage of an illness or a condition. So-called neuropsychiatric diagnoses have the capacity to relieve suffering to shortcomings and in some cases even provide rewards, such as medication or permission for sick leave (Carone, Iverson, & Bush, What consequences will an increase of medicalization of human problems infer on how we conceptualize relationships and social life? To diagnose peoples' vulnerability foremost as biomedical disorders may lead to marginalization. Humans are social beings and a great deal of our psychological distress might originate from social and close relationships early in life. Instead of making the window to “normality” shrink we need to broaden our views on human growth and human conditions.


Attention-deficit/hyperactivity disorder (ADHD) is a common, early-onset and enduring developmental disorder whose underlying etiological and neurobiological processes are the current focus of major research. Research strategies have made considerable effort in elucidating the complex genetic architecture of ADHD and indicate various pathways from genotype to phenotype. Understanding ADHD as a neuropsychiatric disorder enabled to investigate markers of neural activity as endophenotypes to better explain the link from gene to symptomatology . Overcoming the originally rather restrictive requirements for an endophenotype, imaging genetics studies are supposed to offer a much more flexible and hypothesis-driven approach towards the etiology of ADHD. Although 1) ADHD often persists into adulthood, thus remaining a prevalent disorder, and 2) imaging genetics provides a promising research approach, a review on imaging genetics in adult ADHD – as available for childhood ADHD (Durston 2010) – is lacking. In this review, therefore, findings from the few available imaging genetics studies in adult ADHD will be summarized and complemented by relevant findings from healthy controls and children with ADHD that are considered important for the adult ADHD imaging genetics approach. The studies will be reviewed regarding implications for basic research and possible practical applications. Imaging genetics studies in adult ADHD have the potential to further clarify pathophysiological pathways and mechanisms, to derive new testable hypotheses, to investigate genetic interaction effects and to partly influence practical applications. In combination with other research strategies, they can incrementally foster the understanding of relevant processes in a more comprehensive way. Current limitations comprise the incapability to discover new genes, a high genetic load in patients potentially obscuring the effect of single candidate genes, the mostly unknown heritability of the endophenotype and the heterogeneous manifestation of ADHD. Attention-deficit/hyperactivity disorder (ADHD) represents a common, early-onset and enduring neurodevelopmental disorder with a worldwide-pooled prevalence of 5.3% in childhood and adolescence . In adulimaging genetics approach neuroimaging data are treated as endophenotypes [Research strategies have made great efforts in elucidating the complex genetic architecture of childhood and adult ADHD , 8; assoenotypes , 11, whienotypes ): variatenotypes ) when imAlthough the endophenotype concept for neuropsychiatric disorders  was rathAlthough 1) ADHD often persists into adulthood, thus remaining a prevalent disorder, and 2) imaging genetics provides a promising research approach, a review on imaging genetics in adult ADHD – as available for childhood ADHD  – is laca Although this distinction is arbitrary and may not always be unambiguous, it should help to better organize the available data. Table Literature searches using available data bases  were conducted to find imaging genetics studies in adult samples of ADHD till May 2013). Eight studies  were then classified into two categories, i.e. cognitive and affective-motivational approaches, depending on whether they applied cognitive or emotional-motivational paradigms.013. EighPatients with childhood and adult ADHD show impairments in different cognitive domains , 19 whicContinuous performance tasks  involveIn these tasks, subjects are required to maintain or manipulate information in memory to fulfil specific experimental conditions. In an fMRI study, Brown et al.  applied These tasks require subjects to ignore specific (task-irrelevant) information to perform the experimental conditions correctly. In an ADHD group, Brown et al.  investigIn the emotional domain, ADHD patients also display various disturbances ; howevera priori expected increased ventral striatal activity in controls vs. ADHD patients, no effect of the haplotype could be discerned.Hoogman et al.  applied Paloyelis et al.  argued aAs the number of available imaging genetics studies in adult ADHD is limited so far, we will shortly refer to exemplary findings in healthy subjects and children. Especially studies on emotional processing are promising. Behavioral studies reveal that ADHD children are less accurate in classifying emotional facial expressions –38. On sNeuroimaging studies in healthy participants provided evidence for distinct pathways for explicit versus implicit processing of emotions in faces  and voicApart from dysfunctional emotional processes, other endophenotypes need to be considered in further studies, e.g., neuropsychological deficits, such as measures of attention, executive function and processing speed . FurtherSo far, imaging genetics studies in adult ADHD are – compared to other lines of ADHD research – rather scarce and research is still at its beginning. Nonetheless, the available findings provide an outlook on the potential chances of this research approach which – in combination with complementary approaches – may help to increase our knowledge about the pathophysiological pathways in adult ADHD. Yet, several limitations need to be considered as well (see below).The imaging genetics approach provides an improved insight into possible, important pathophysiological pathways and it allows deriving testable hypotheses that promote a better understanding of the neurobiology of normal and pathophysiologically altered behavior. Studies reporting that gene variants influence neural markers independently of diagnostic status e.g., , 25, 32), 3225, 3Candidate genes that have been replicated empirically in large-scale association studies  can be tested regarding their functional impact in a hypothesis-driven approach. These genetic findings indicate an involvement of specific psychopathological pathways which can be further investigated in imaging genetics studies: For example, the association of the DAT 9-repeat allele with adult ADHD led to our hypothesis that this allele – which influences the frontal-striatal loop – may be associated with a concurrent less efficient prefrontal functioning in our adult ADHD sample .Imaging genetics has the potential to be used in a translational manner, thus allowing basic findings to influence practical applications. If specific gene variants are highly associated with altered brain activation in specific cognitive or emotional domains, a more tailored pharmacological or psychotherapeutic intervention can be chosen, thus offering new treatment targets . Mattay Complex interactive effects of several genes with individually small impact  have beein vivo and in vitro investigations, animal models, combined PET-fMRI measurements) helps to identify important pathophysiological mechanisms. For example, the research on the risk haplotype in the LPHN3 gene originated from pedigree linkage studies in a Columbian genetic isolate [Imaging genetics is one element that in combination with other – also distant – research strategies . This mOften, the question remains whether the applied imaging paradigms are in fact heritable. To date, a few studies already indicate heritability of the brain activation during working memory , 68 and As dopaminergic candidate genes have been extensively investigated in molecular genetics studies , 70, imaADHD shows a considerable overlap in clinical symptoms  with BPD. High genetic correlations for these disorders support the hypothesis that ADHD in childhood might even be a precursor of BPD in adulthood . Thus, fAnother aspect which is often not considered in current research literature on ADHD is its rather heterogeneous manifestation. Refining research in this respect might reduce contradictory results and simultaneously enhance comparability between studies. Also in this context, imaging genetics could be one approach to define ADHD subtypes that are more strongly related to differences in underlying neurobiology than current “clinical” diagnostic classifications. Some studies focusing on DSM-IV subtypes  did not provide any significant effects , 73, whiThe review is based on only a few studies which prevents drawing strong unequivocal conclusions. These studies are also rather diverse with regards to paradigm, endophenoype measurement and investigated candidate genes.Taken together, current literature on the genetics of ADHD is not conclusive. Here, imaging genetic studies could come into play and lead to new insights regarding the complex and diverse pathways from the level of genetic vulnerability to overt clinical symptoms. Also, presently, the reported research findings are not directly applicable in clinical practice for adult ADHD  which is an aspiration for the near future. As in 30% of ADHD patients stimulant treatments do not lead to symptom improvements , furtheraOne study [ne study  was not


Nonylphenol (NP) belongs to the family of endocrine disruptors, and it is widely used in industrial applications and is ubiquitous in daily foods. Animal studies have suggested that NP exposure might promote motor hyperactivity, likely by causing deficits in dopaminergic neurons. However, research assessing NP exposure and epidemiology studies on human populations are limited. The aim of this study was to explore the association between child NP exposure and ADHD while considering particular covariants, such as lead levels and dopamine-related gene variations.DRD4, and dopamine transporter, DAT1). Socio-demographic variables, maternal lifestyle factors during pregnancy and family medical history were obtained using a questionnaire.A case-control study was conducted on patients with clinically diagnosed ADHD; the Swanson, Nolan and Pelham, Fourth Revision (SNAP-IV) questionnaire was used to identify normal controls aged 4–15 years. Participants were examined for urinary NP concentrations, blood lead levels, and select single-nucleotide polymorphisms of two dopamine-related genes . No significant difference in urinary NP concentration was found between the children with ADHD and the control subjects . ADHD was significantly more prevalent among males in this study . The analysis was repeated after excluding the females, but this had no effect on the association between NP and ADHD. The regression model, including or excluding females, indicated no increased odds of having ADHD in the context of NP exposure after adjusting for covariants.A total of 97 children with doctor-diagnosed ADHD and 110 normal controls were enrolled. The blood lead levels in both groups were similar (1.57±0.73 vs. 1.73±0.77 μg/dL, This study indicated that NP exposure might not promote ADHD in children, even though children in Taiwan had relatively high levels of NP compared to those reported previously and those in developed nations. Nonylphenol (NP) and its parent compound, nonylphenol polyethoxylate (NPnEO), are used in various manufacturing processes and in a wide range of products to which humans are exposed –5. The aHumans may be exposed to NP through drinking water; the intake of contaminated foods; the inhalation of air; and absorption via the skin , 16. NP DRD4) and dopamine transporter (DAT1) genes and ADHD have been most frequently verified [Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood neurobehavioral conditions, with a prevalence ranging from 5.9%-7.1% worldwide and from 7.5%-9.9% in Taiwan , 24. ADHverified . Lead isverified . Low-levverified , 33–35.Animal studies have revealed that the chronic application of NP sensitizes mouse brains and causes neuronal apoptosis . IntraciThe study protocol was approved by the Taipei City Hospital institutional review board. All participants gave verbal or written assent. Written informed consent was obtained from the participant’s parents or guardians. We recruited subjects between 4 and 15 years of age in outpatient waiting rooms at Taipei City Hospital. The case subjects in this study were children with ADHD identified by board-certified pediatricians or psychiatrists after at least a three-visit clinical assessment. Consecutive children admitted for initial or follow-up ADHD treatment were recruited as cases during the study period, with the exclusion criteria of neurological deficits or mental retardation. The diagnosis of ADHD was performed in accordance with the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised criteria (DSM-IV-TR) .Control subjects were recruited by randomly selecting healthy children without ADHD aged 4–15 years who utilized Taipei City Hospital for non-ADHD-related visits during the same study period. The same exclusion criteria for the cases were applied to the controls. Controls were screened for the absence of ADHD symptoms based on assessments of their behavior at home and in the classroom by the parent(s) and teachers, respectively, according to the Chinese version of the Swanson, Nolan and Pelham, Fourth Revision (SNAP-IV) questionnaire –46. The Ninety-seven ADHD subjects (N = 97) and one hundred ten normal controls (N = 110) were recruited. The response rates were 54.8% (97/177) and 52.6% (110/209) in the case and control groups, respectively. In this case-control study, the participating subjects also were investigated by questionnaires regarding demographic features, lifestyle factors of the mother during pregnancy and family history of nervous system diseases. Subjects provided a spot urine sample and blood  sample during the clinic visit.4- Nonylphenol (p-isomers >85%) was obtained from Fluka . Methanol, n-hexane, acetone, acetonitrile, hydrochloric acid, acetic acid, and ammonium acetate were LC grade, and all were obtained from Merck . β-Glucuronidase (type H-2) was purchased from Sigma-Aldrich (USA). Deionized water, obtained using a Millipore water purification system , was prepared before use and was collected in a glass container.High-performance liquid chromatograph (HPLC) coupled with a fluorescence detector  was used for NP analysis. The reverse-phase column was a Luna C18 (250 x 4.6 mm) with a 5-μm particle size. The isocratic mobile phase was a mixture of acetonitrile and water  with a 1.0 mL/min flow rate. The fluorescence detector was operated at an excitation wavelength of 275 nm and an emission wavelength of 300 nm. The samples were injected at volumes of 20 μL.This study adopted the same NP analytical method used previously in this lab . Before To avoid contamination of NP, glassware was used for the urine collection for both the case and control groups. Urine samples were sealed, chilled, and transported to the lab immediately. No NPnEO (which is biodegraded to NP)-containing detergents and plastics were used during sample collection, preparation and analysis. NP concentrations were adjusted using creatinine concentrations to correct for variable urine dilutions in the spot urine samples. Urinary creatinine concentrations were determined using a commercially available diagnostic enzyme method  that is based on a modified Jaffe reaction . The conTM, Norway) was used to verify the precision and accuracy of the analytical measurements. For the BLL measurements, the LOD was 0.001 μg/dL with a CV of 3.2%.Peripheral blood was drawn using a syringe or venoclysis needle, which was then sealed in a heparin-containing vacuum tube and immediately transported at 4°C to the laboratory. One milliliter of whole blood was frozen separately and stored for lead analysis. The BLLs were measured using inductively coupled plasma-mass spectrometry . Trace Elements Serum L-2 (Seronorm2) greater than 0.995, and each specimen was calibrated and adjusted using a blank sample. The results are reported as the mean of two replicate measurements. Moreover, quality control samples were analyzed in each batch.The following quality controls were adopted for the NP and BLL measurements: a minimum of five calibration concentrations were used for each batch with correlation coefficients  and stored at room temperature until analysis.DRD4 and DAT1 were selected by screening the CHB (Han Chinese in Beijing) panel from the HapMap database (http://hapmap.ncbi.nlm.nih.gov/). To avoid redundancy and to obtain complete genetic coverage, we evaluated linkage disequilibrium patterns and set a maximum r2 threshold of 0.8 for all SNPs that possessed a minor allele frequency (MAF) ≥0.05. The non-synonymous SNPs were further inspected using the University of California at Santa Cruz (UCSC) genome browser (http://genome.ucsc.edu/). For the tagged SNPs, MAF values ≥0.1 were used to check the genetic variations in the CHB by browsing the 1000 GENOME database (http://www.1000genomes.org/).Genotype analyses with haplotype-tagging SNPs of DRD4 and DAT1 SNPs was performed using the MassARRAY Platform  at the VYM Genome Research Center, National Yang-Ming University. Amplifications were performed in a 384-well polymerase chain reaction system at a minimum concentration of 10 ng/μL DNA. The genotypes were tested for deviation from Hardy-Weinberg equilibrium, and associations were analyzed using standard chi-square goodness-of-fit tests (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl).Genomic DNA from peripheral blood leukocytes was extracted by using a DNA mini kit . DNA from saliva was isolated using a QIAamp DNA Mini Kit  according to the manufacturer’s instructions. Genotyping of the DRD4 and DAT1 were measured in this study, and the other variables were obtained from clinical records or questionnaires completed by the parents.We examined covariates and potential confounders for the association between NP exposure and ADHD. Predictors were chosen based on their association with ADHD in previous studies. The following variables were considered as potential confounders: BLLs, dopamine-related gene variations, age, gender, BMI, maternal age at childbirth, gestational age at birth (<37 weeks or ≥37 weeks), parental education (high school education and below or college or advanced training), maternal smoking during pregnancy (yes or no) and maternal drinking during pregnancy (yes or no) , 49–53. p<0.05. Logistic regression analyses of NP concentrations and ADHD with and without adjusting for covariant factors were conducted to investigate the odds ratio. Covariates were included in the multivariate analyses if they were related to ADHD at p<0.1. A covariate was controlled if the adjusted and unadjusted coefficients between NP exposure and ADHD differed by 10% [th, 25-75th and >75th percentiles.SPSS version 17.0 was used for the statistical analysis. Measurements below the LOD were given a value corresponding to LOD/2. We assessed the significance of differences between the case and control groups using the 2-sided nonparametric statistical Mann-Whitney U test for consecutive data and chi-squared tests or Fisher’s exact test for categorical data, where appropriate . The stad by 10% . Dose-re2 = 16.7, p<0.01). The mean ages (±SD) of cases and controls were 8.9±2.8 years and 8.9±2.0 years, respectively. Children with and without ADHD did not differ in terms of age, BMI, maternal age at birth, and maternal smoking during pregnancy. Age-related differences were examined, and no differences in the effect estimates were observed.p<0.1, only maternal education levels and maternal drinking during pregnancy had a greater than 10% coefficient difference in the unadjusted and adjusted regression analyses, and these two variables were adjusted in the logistic regression model.Control children had significantly higher paternal and maternal education levels compared to children with ADHD. This study also found an association between maternal drinking during pregnancy and ADHD. ADHD cases were significantly associated with a family history of nervous system diseases compared with the reference subjects. Among those variables with DRD4 and DAT1 among the study participants. We observed a nominal significant difference in a DRD4 gene polymorphism (rs752306) between the case and control groups. However, the difference may have resulted from the limited number of subjects. Logistic regression models of NP and ADHD were estimated after including dopaminergic gene variations (those with p<0.1) to determine whether genetic variation influences the risk of having ADHD. Variations in dopaminergic genes did not modify the association between NP exposure and ADHD in this study.p = 0.15). There was a small difference  in the association between NP exposure and ADHD after adjusting for BLLs compared to the unadjusted association.There were challenges involved in obtaining blood during participant recruitment, especially for school-aged ADHD participants, and the difference in BLLs between the case and control groups was not significant. Therefore, we discontinued the blood collection after we had recruited 146 subjects (44 cases and 102 controls). The BLLs of these 146 subjects ranged from 0.44–4.71 μg/dL , and leap = 0.43). Moreover, logistic regression analyses, with females included and excluded, suggested that children with creatinine-adjusted NP concentrations higher than the median may not present with a greater risk of having ADHD compared to children with concentrations below the median (Urinary NP was detected in 97.6% of the participants . The cone median . The oddp<0.01), with few positive maternal drinking subjects reported in the control group. After exclusion, the limited number of participants with in utero alcohol exposure did not affect the adjusted odds ratio in the logistic regression analysis.We detected a significant association between maternal drinking during pregnancy and ADHD (p<0.01); ADHD was approximately three-fold more likely to be diagnosed in boys than in girls [p = 0.67, data not shown). Higher urinary NP levels did not increase the odds ratios between NP and ADHD when females were either included or excluded . The BLLs in this study were lower than those in the other two studies in Taiwan, which reported measurements of 5.50±1.86 μg/dL for 934 primary school children in 2002 and a range from 1.97 to 2.49 μg/dL for children 5–9 years of age in 2012 [Lead exposure alters the dopamine system, which is relevant to the pathogenesis of ADHD , 65. Low in 2012 , 68. LeaA previous study in this lab assessed the NP exposure of pubertal students aged 10.9–13.6 years and reported a geometric mean (GM) urinary NP level of 1.27 μg/g cr.; 30% of the urine samples were positive for NP . In thisThe differences in NP levels between our study and other reference values reported in the Belgian and American data may be caused by several factors. First, NPnEO, which are biodegraded to NP, are massively produced and widely used in Taiwan –75. SecoWe report an absence of association between urinary NP concentrations and ADHD and no increased odds of ADHD for children with higher NP levels. The regression analyses, with and without excluding females, suggested that higher NP exposure may not promote the risk of having ADHD. Furthermore, no dose-response effects were observed.According to Muller’s pharmacokinetic study, a bioavailability of 20% and a half-life of 2–3 h in blood were reported for NP. Moreover, only 10% of the applied dose is excreted in the urine [Estimated daily exposure of NP (μg/day/Kg b.w.) = urinary NP levels (μg /L) x urine excretion per day (L/day) /10% NP exposure excreted through urine /body weight of participants (Kg)The estimated daily exposure to NP in this study was lower than the tolerable daily intake (TDI) of 5 μg/day/Kg b.w. proposed by the Danish Institute of Food Safety and Toxicology . MoreoveThis study has a number of strengths. To the best of our knowledge, this is the first published study related to the association between pediatric urinary NP concentrations and ADHD in Taiwan. Moreover, the SNAP-IV questionnaire, a tool with acceptable reliability, was used to screen children with suspected ADHD. The diagnosis of ADHD was confirmed through an extensive evaluation based on the DSM-IV-TR clinical diagnosis performed by pediatricians or psychiatrists. Chances of misclassification between ADHD and non-ADHD were therefore minimal. In addition, we examined or adjusted for various important factors, including dopamine-related gene polymorphisms, exposure to lead, several socioeconomic indicators and maternal lifestyle factors.However, this study also has several limitations. The limited sample size was related to the challenge of recruiting school-age children, especially those with ADHD, to participate in the study. The limited participation rate may be another limitation. Taipei City Hospital is a metropolitan hospital that serves the local population and accepts referrals from all the administrative districts in the city. In addition, 97.1% of the participants in the present study live in this metropolitan area. The cases and controls were recruited from the general pediatric clinics, not specific ADHD clinics, at the same hospital. Because attendance at Taipei City Hospital and the chance of being selected for the study were not dependent on NP levels, the chance of selection bias was probably low . In addiThis case-control study found that NP exposure, at the estimated dosage of ~1.65–2.48 μg/day/kg b.w., was not a risk factor for ADHD in school-age children in Taiwan after adjusting for confounding factors. No differences were observed in BLLs between children with and without ADHD. More studies are warranted to further confirm the lack of a relationship between NP exposure and ADHD in children.


Previous studies suggested that the presence of ADHD in children and young adolescents may affect the development of personality. Whether or not the persistence of ADHD in adult life is associated with distinct personality patterns is still matter for debate. To address this issue, we compared the profiles of the Temperament and Character Inventory (TCI) that assesses personality dimensions in 119 adults ADHD and 403 controls.ANCOVA were used to examine group differences (controls vs. ADHD and ADHD inattentive type vs. ADHD combined + hyperactive/impulsive types) in Temperaments and Characters. Partial correlation coefficients were used to assess correlation between TCI and expression and severity of symptoms of ADHD.High novelty seeking (NS), harm avoidance (HA) and self-transcendence (ST) scores as well as low self-directedness (SD) and cooperativeness (C) scores were associated with ADHD diagnosis. Low SD was the strongest personality trait associated with adult ADHD. Cases with the ADHD inattentive type showed higher HA and lower SD scores compared to the combined and hyperactive/impulsive types. High HA scores correlated with inattention symptoms whereas high NS and ST scores were related to hyperactive symptoms. Finally low SD and high NS were associated with increased ADHD severity.Distinct temperaments were associated with inattentive versus hyperactive/impulsive symptoms supporting the heterogeneous nature of the disorder. Attention-deficit hyperactivity disorder (ADHD) is characterized by impaired attention control, impulsiveness and hyperactivity (motor restlessness). This disorder affects 3 to 7 % of children and persists in adulthood in roughly 30 to 60 % of subjects . A deletAmong the tools used to assess personality, the Temperament and Character Inventory (TCI), a self-report questionnaire assessing four dimensions of temperament (novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (P)) and three dimensions of character (self-directedness (SD), cooperativeness (C) and self-transcendence (ST)), based on the Cloninger’s biopsychosocial theory of personality, has aroused growing interest in ADHD subjects . Its devCharacters are believed to represent more complex cognitive processes and refer to individual differences in goals, self-concepts and values. Being tightly linked to environmental influences, character dimensions may vary as a function of developmental stages during lifespan.Previous studies on temperaments in adults and children suffering from ADHD led to highly comparable data showing high scores on NS, conceived as the tendency to be impulsive and irritable versus rigid and stoical, high scores on HA, defined as the tendency to be pessimistic and anxious versus optimistic and risk-taking, low scores on P, assessing the tendency to be persevering and ambitious versus easily discouraged and indolent, and low scores on RD defined as the tendency to be sociable and warm versus aloof and cold , 10–21.In terms of character patterns, earlier data reported that ADHD subjects differ from controls by low SD, referring to the tendency to be blaming and inept, low C associated with hostility and opportunism, and high ST describing people who are intuitive and insightful , 21, 22.However, ADHD is not a clinically homogeneous condition. In recent years, three main subtypes (according to DSM-V) have been recognized, the predominantly inattentive presentation if the subject mainly has symptoms of inattention, the predominantly hyperactive-impulsive presentation if mainly symptoms of hyperactivity-impulsivity are present, and the combined presentation where both criteria of inattention and hyperactivity-impulsivity are present. To date, several studies have investigated which personality dimension is associated with specific subtypes of the disorder however leading to controversial data , 23–26. Some studies using the Five Factor Model (FFM) of Personality also investigated the link with the severity of ADHD, but this has been poorly explored using the TCI leading to conflicting data . For insIn conclusion, although concordant results emerged when comparing controls to ADHD subjects, this is not the case when looking at the different subtypes and severity of ADHD. In this perspective, we explored the association between ADHD subtypes and temperament and characters in adult life as well as that between these personality patterns and severity of the disease in a large community-based sample of adult ADHD cases compared to healthy controls. Based on the above-mentioned literature, we were expecting to find high NS, HA and ST scores as well as low SD and C in subjects suffering from ADHD. We also hypothesized that deviation in NS and in HA would be related to hyperactive/impulsive and inattentive symptoms respectively. Finally, we were expecting to find an association between low SD and C scores with severity of ADHD.One hundred and nineteen outpatients with adult ADHD were recruited in a specialized center for the diagnosis and care of adult ADHD patients at the University Hospitals of Geneva. ADHD diagnosis was made according to the DSM-IV criteria based on a clinical interview with trained psychiatrists . Six or more symptoms of inattentive and/or hyperactive-impulsive symptoms were required and should be present before 7 years of age. The number of symptoms was used to determine the ADHD subtype as described by Prada et al. . BrieflyMost of the adult ADHD patients (N = 89) were addressed by either general practitioners or psychiatrists for an initial assessment and for a suspicion of ADHD and were thus free of any psychopharmacological treatment at the time of their recruitment; although some of them previously received antidepressants for previous major depressive disorder. The remaining 30 subjects were already diagnosed with ADHD and were, for most of them, taking psychostimulants when reaching our tertiary center.The comparison group included 403 subjects recruited from the general population in the Blood Donor Center of the University Hospitals of Geneva and School of Dentistry at the University of Geneva.Controls and ADHD patients with neurological conditions such as epilepsia were excluded from the study.The study was approved by the ethics committee of Geneva University Hospitals. Informed written consent was obtained from all participants.A semi-structured interview assessing childhood and adulthood ADHD based on DSM-IV criteria: “Entretien diagnostique pour le TDAH chez l’adulte” (DIVA)  as well Finally, ADHD subjects completed the TCI. The TCI is a 240-items  self-report questionnaire evaluating temperament and character dimensions. Each question should be answered by yes or no, assessing the four dimensions of temperament  and the three dimensions of character . Besides the 7 main scales, the TCI also provides a number of subscales (3 to 5) for each of the temperaments and characters (which will not be taken into account in the current paper). The Cronbach’s alpha was good for each of the TCI subscales with values comprised between 0.89 and 0.93.All of the controls completed the TCI. Among them, 191 subjects were also screened for Axis I disorders for main diagnosis and comorbidities (142 negative), using the Mini International Neuropsychiatric Interview .One-way analysis of covariance (ANCOVA) with adjustment for age, included as a continuous was used to compare the Temperaments’ and Characters’ means between ADHD and controls.Given the high frequency of psychiatric comorbidities in adults suffering from ADHD, and in order to test a "real life" hypothesis, two analyses were performed. The first concerned the whole sample: ADHD subjects without the exclusion of psychiatric comorbidities and all controls. In this analysis, controls corresponded to the notion of non-ADHD. The second analysis was made in ADHD subjects without psychiatric comorbidities and controls after exclusion of psychiatric disorders.ANCOVA was also used to compare the Temperaments’ and Characters’ means between ADHD with the predominantly inattentive type and ADHD with the two other types (hyperactive/impulsive + combined). Given the small number of subjects suffering from the predominantly hyperactive/impulsive ADHD subtype (n = 8), these subjects were pooled with subjects suffering from the combined subtype (N = 65) for statistical purposes.Finally, within ADHD subjects, partial correlation coefficients were computed between TCI temperaments and characters and ADHD symptoms, and severity with adjustment on age and gender. Partial correlation coefficients is calculated between one given variable (ex: NS) and a variable after removing the effects of all other variables entered into the model.As characters are believed to be highly influenced by environmental factors, and thus vary during different stages of lifespan, we wondered whether childhood maltreatment would be associated with characters. Partial correlation coefficients were thus used to assess strength of correlation between different types of childhood maltreatments and TCI temperaments and characters within ADHD subjects.When data was not normally distributed  Box-Cox transformation was used to take the appropriate remedial actions. This procedure helps to identify an appropriate exponent (Lambda = l) to use to transform data into a “normal shape.” The power to which all data should be raised is determined by the Lambda value. To do so, the Box-Cox transformation seeks from Lambda = −5 to Lamba = +5 until the best value is found. Then the appropriate action to transform the data is taken. STATA SE v.12.0 was used for the analyses and p value of ≤0.05 was considered as significant.(1/521) = 28.3; p < 0.0001), higher HA scores (F(1/521) = 54.2; p < 0.0001), higher ST scores (F(1/521) = 9.2; p = 0.003), lower SD scores (F(1/521) = 269.7; p < 0.0001) and lower C scores (F(1/521) = 26.4; p < 0.0001). Similar results were obtained (same magnitude of effect size) after exclusion of psychiatric comorbidities in ADHD subjects and exclusion of psychiatric disorders in controls (Table Table /521 = 28(1/118) = 9.3; p = 0.003 and F(1/118) = 5.2; p = 0.024)  of personality showing that ADHD subjects whatever is their age display deviation in several personality dimensions . In a reOur results also reveal that HA and NS scores may differentiate inattentive from hyperactive/impulsive ADHD subtypes , 53, 54.In conclusion, our study offers a compelling picture of personality deviations in ADHD and how they relate to symptom dimensions. Longitudinal studies are clearly needed in this field in order to better understand the complex interplay between personality and ADHD symptoms.ADHD, Attention-deficit hyperactivity disorder; ANCOVA, One-way analysis of covariance; ASRS, Adult ADHD Self-Report Scale; C, cooperativeness; CTQ, Childhood Trauma Questionnaire; DIGS, Diagnostic Interview for Genetic Studies; DIVA, Entretien diagnostique pour le TDAH chez l’adulte; FFM, Five Factor Model; HA, harm avoidance; NS, High novelty seeking; P, persistence; RD, reward dependence; SD, self-directedness; ST, self-transcendence; TCI, Temperament and Character Inventory; WURS, Wender Utah Rating Scale.


Background: Abundant work indicates ADHD abnormal posterior brain structure and function, including abnormal structural and functional asymmetries and reduced corpus callosum size. However, this literature has attracted considerably less research interest than fronto-striatal findings.Objective: To help address this imbalance, the current study replicates and extends our previous work showing abnormal parietal brain function in ADHD adults during the Conner’s Continuous Performance Test (CPT).Method: Our previous study found that ADHD adults had increased rightward EEG beta (16–21 Hz) asymmetry in inferior parietal brain regions during the CPT (p = 0.00001), and that this metric exhibited a lack of normal correlation  with beta asymmetry at temporal–parietal regions. We re-tested these effects in a new ADHD sample and with both new and old samples combined. We additionally examined: (a) EEG asymmetry in multiple frequency bands, (b) unilateral effects for all asymmetry findings, and (c) the association between EEG asymmetry and a battery of cognitive tests.Results: We replicated our original findings by demonstrating abnormal rightward inferior parietal beta asymmetry in adults with ADHD during the CPT, and again this metric exhibited abnormal reduced correlation to temporal–parietal beta asymmetry. Novel analyses also demonstrated a broader pattern of rightward beta and theta asymmetry across inferior, superior, and temporal–parietal brain regions, and showed that rightward parietal asymmetry in ADHD was atypically associated with multiple cognitive tests.Conclusion: Abnormal increased rightward parietal EEG beta asymmetry is an important feature of ADHD. We speculate that this phenotype may occur with any form of impaired capacity for top-down task-directed control over sensory encoding functions, and that it may reflect associated increase of attentional shifting and compensatory sustained/selective attention. The other seeks to indulge as much detail as possible in order to generate a prolonged sensory immersive experience.If a person wants to find an apple “to eat” on a cluttered countertop, it is task-adaptive to identify that stimulus using the minimal sensory detail required. Here, the apple’s constituent esthetic characteristics and/or peripheral information are task-extraneous. Alternatively, if an artist wants to paint a still-life portrait of said apple, they should indulge as much sensory detail as possible. One approach seeks to Our current line of research began with the simple precept that the first of these approaches (“to identify a stimulus”) is critical for task-directed actions, and that mobilizing this task-specialized manner of information processing likely depended on the coordinated functioning of multiple distributed brain systems, such as: 1) verbal working memory (VWM) to sequence, direct, maintain, and update task directives [with possible support from spatial working memory (SWM) to model integrated plan steps]  verbal w, (2) SWMWe hypothesized that the coordinated functioning of such elements formed an emergent task-directed brain-system or neural context that optimized multiple distributed brain functions toward task-directed actions  , 11. We We first examined this hypothesis in ADHD adults using behavioral laterality paradigms. These demonstrated: an ADHD bias toward non-verbal sensory encoding, greater RH contribution to processing task stimuli, associated linguistic impairments, and abnormal interhemispheric interaction , 13, andAlthough not yet widely understood, these findings are well aligned with extant ADHD literature. Slow naming speed is identified in ADHD –27, whicWith complex executive function (EF) tasks the literature is more variable, showing diffuse effects mainly consistent with variable weaknesses across multiple brain systems –49. Neveper se, but rather more broadly reflective of any form of impaired task-directed brain-system functioning. Consistent with this, rightward biased brain function has been reported across multiple circumstances linked to attention difficulties, and that are often comorbid with ADHD   –70. AccoTo pursue this goal, we previously evaluated whether rightward biased information processing in ADHD was distinct from the similarly described characteristic in reading impaired samples . At thatThe current study’s goal was to replicate these EEG beta findings in a larger ADHD sample and extend these results by newly evaluating: (a) EEG asymmetry across multiple frequency bands and brain regions, (b) whether asymmetry in ADHD can be attributed to unilateral activations, (c) the correlations among asymmetry effects, and (d) the associations between EEG asymmetry and cognitive ability. This last goal is critical in that, as noted, our conceptual framework suggests that increased RH contribution to sensory processing could result from multiple and variable impairments across a set of integrated brain functions that serve task-directed actions. By examining the association between sensory processing asymmetry in ADHD and a battery of cognitive tasks, we hope to gain insight into what aspects of putative task-directed brain-system functioning might be most proximal to manifest rightward biased information processing in ADHD. These study goals are summarized in Table All subjects for the current study were participants in a previous UCLA ADHD family genetics study , 78. OurAfter receiving verbal and written explanations of study requirements, participants provided written informed consent approved by the UCLA Institutional Review Board. Through the UCLA ADHD Genetics Study, all subjects were screened for ADHD and other psychiatric disorders via direct interviews using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version  supplemHandedness was assessed with a shortened version of the Edinburgh Handedness Inventory . This haSubjects were excluded based on the following criteria: past or current documented neurological disorder, a significant head injury resulting in loss of consciousness, a diagnosis of schizophrenia, schizophrenia spectrum disorders, autism, or an estimated Full Scale IQ <80. We did not directly assess for language impairment in our sample. However, an assessment of group differences in several linguistic measures was performed to help rule out language impairment in the ADHD sample.Inclusion criteria for the present study required a lifetime diagnosis of ADHD, and for non-ADHD controls, no evidence of past or current ADHD . In our original study, we required a current rather than lifetime diagnosis of ADHD. This change reflects an increased interest in the brain function characteristics of individuals who present with childhood ADHD, regardless of long-term outcomes. Twenty-three of 90 ADHD subjects in the current study met criteria for lifetime ADHD, but not current . Five ADHD subjects were on stimulant medication and five were on medication for depressive symptoms (SSRIs). The impact of medicated subjects was directly assessed for all reported analyses. See Table Typical testing procedures for the UCLA ADHD genetics study involved a mother and/or father and two ADHD affected offspring coming to UCLA for single visit . During the visit, each family member underwent a clinical, cognitive, and EEG testing battery, with the order of delivery of each component determined by logistical considerations. However, during EEG testing the Conners’ CPT  was alwahttp://www.manscaneeg.com) designed to identify dead and bad channels, vertical and horizontal eye movements, saturation, muscle and movement artifact, and line frequency noise. Subsequent to this automated procedure, an experienced EEG technician visually inspected all data and identified any residual contaminants. Next, continuous EEG was broken into 1-s epochs and artifact-containing epochs were removed on a channel specific basis. Remaining artifact free epochs were then Fast Fourier Transformed (FFT) using MANSCAN EEG software, which uses a Welch’s Periodogram approach (2) from 1 to 21 Hz was exported in 1 Hz bins . Absolute power between 1–4 Hz (Delta), 4–8 Hz (Theta), 8–10 Hz , 10–12 Hz , 12–16 Hz (beta1), and 16–21 Hz (beta2) frequencies was averaged for each electrode. These bands are non-overlapping. For example, beta1 extends up to the 15–16 1-Hz bin, while beta2 begins at the 16–17 1-Hz bin. Technicians involved in the EEG recording and processing were blind to ADHD diagnostic status.EEG recording (256 samples/s) was carried out using 40 silver chloride electrodes using the International 10/20 locations and was referenced to an average of signals recorded separately at each ear lobe. Eye movements were monitored by electrodes placed on the outer canthus of each eye for horizontal movements and above the eye for vertical eye movements. EEG was recorded during the Conners’ CPT II , lastingapproach . We specOur primary interest was to replicate and extend our previous finding of R > L beta2 asymmetry in the inferior parietal region of adults with ADHD during the CPT . Thus, tLastly, in our efforts to further characterize the nature of atypical functional asymmetry in ADHD, the current study also examined separate left and RH activations for AIs that showed significant group differences. To generate EEG power measures for individual electrodes and frequency bands of interest, power in a target frequency at a given electrode was divided by the averaged total power (1–21 Hz) across the scalp (26 electrodes in standard 10–20 positions). This electrode-set did not include electrodes placed inferiorly to the axial plane of the 8/7s or electrodes used for detecting eye artifact . These individual electrode measures will be referred to as “globally normalized” (GN) power.d′) indicating accuracy adjusted for false alarms.The CPT required subjects to monitor a central fixation on a computer screen while single capital letters are sequentially and centrally presented during 6 continuous blocks of 20 trials with either 1, 2, or 4 s inter-stimulus intervals (ISIs) (2 blocks for each ISI). Total task time is 15 min. The order of ISI block presentation is randomized within subjects. The task requires subjects to press the space bar using their dominant hand with every letter presentation except for the letter “X.” The “X” occurs on 10% of the trials within a given ISI block. Behavioral performance was assessed using the following standard CPT measures : (1) compost hoc we also examined CPT P8–P7 asymmetry in multiple frequency bands to test the “beta specificity” of this effect. In the original study we also examined correlations between the beta2 P8–P7 AI  and other AIs in the beta band, and tested the association between P8–P7 beta2 asymmetry and CPT task performance. The current study builds on these approaches.In the original study we tested beta asymmetry effects; however, as a (1)n = 43) and with our current full sample comprised of both the original and newly added ADHD participants (n = 31 + 43 = 74).To examine the robustness of our previously identified rightward beta2 asymmetry in the inferior parietal region (P8–P7) of adults with ADHD during the CPT , we re-tested our original analysis with a new cohort of adult ADHD subjects ((2)Next, in an attempt to further characterize this asymmetry effect, three additional analyses were performed: (a) to assess whether rightward EEG asymmetry in ADHD is specific to the beta2 frequency band at the P8–P7 AI, we examined EEG asymmetry across multiple frequency bands and brain regions, (b) to examine whether uncovered asymmetry effects in ADHD were driven by separate left and/or RH activations, we tested group differences in unilateral right and LH electrodes comprising any AI that showed a group difference, and (c) to further examine whether the EoI was distinct, or associated with other asymmetry effects, we tested correlations between the EoI and any newly uncovered asymmetry findings.p < 0.00001), but not in ADHD subjects (p = 0.49) .These analyses provided an opportunity to directly re-assess two key outcomes from our original study: (1) group differences at the P8–P7 AI were only evident for the beta2 frequency band, and (2) beta2 asymmetry at P8–P7 and TP8–TP7 AIs were highly correlated in controls . For each AI that showed group asymmetry differences, linear regression was used to examine whether EEG asymmetry interacted with ADHD diagnostic status to predict cognitive abilities. Group differences in cognitive abilities were also directly assessed.p = 0.025) and reduced sensitivity (d′: p = 0.02), and (2) in ADHD subjects only, greater rightward beta2 asymmetry at the P8–P7 AI was associated with fewer commission errors (p = 0.048).These analyses allowed us to re-assess two key outcomes from our previous study: (1) ADHD subjects had increased CPT commission errors , results are reported without multiple comparison adjustments. Moreover, in our efforts to further characterize the EoI, our interest was specifically to identify meaningful patterns of EEG-to-behavior effects. Hence, we present these findings without multiple comparison adjustments and limit our interpretation of results to a “pattern level of analysis,” which helps guard against type-1 error. The three statistical methods utilized in the current study are presented below.All analyses were performed using SPSS (v21). All significant findings were re-tested with medication status  entered as additional covariates and the resultant medication adjusted p = 0.11). Moreover, since subjects responded with their dominant hand during the CPT, co-varying for handedness in our EEG analysis also adjusted for any CPT response hand effects.General linear model univariate ANOVA was utilized to examine group differences in EEG asymmetry and cognitive task performance. Outcome measures were entered as the dependent variable, with diagnostic status (ADHD versus Control) entered as a fixed factor, and handedness and the presence of an anxiety and/or mood disorder were entered as covariates  and other EEG asymmetries that showed group differences, and partial correlations were used to this same end in ADHD subjects while adjusting for medication status. Where relevant, we used Fisher’s elations . For thiLinear regression was used in secondary analyses to examine whether ADHD affection-status interacted with EEG asymmetry measures of interest  to predict cognitive abilities. Here, a cognitive measure was entered as the outcome variable, with the following variables entered as predictors: handedness, anxiety-status, mood-status, affection-status, the AI of interest, and an interaction term of affection-status by the AI of interest. In this way, we assessed whether ADHD subjects showed unique associations between EEG asymmetry and cognitive measures. Prior to performing these analyses, we utilized the univariate procedure described above to characterize group differences on cognitive measures used in these secondary analyses Table .Table p = 0.046). With the full sample, the replication of the EoI was highly significant (p = 0.00003) and remained so after adjusting for medication status  in the beta2 band, which is reported due to a conceptual interest.Examination of multiple frequency bands and AIs across the scalp demonstrated several instances of atypical rightward parietal asymmetry in ADHD. Rightward parietal asymmetry in ADHD subjects was evident at the temporal–parietal AI (TP8–TP7) in theta, beta1, and beta2 frequency bands, the inferior parietal AI (P8–P7) in the beta2 frequency band, and the superior-parietal AI (P4–P3) in theta and beta2 frequency bands  to assess association between the EoI and the other AIs that showed group differences. The Fisher r-to-z test: z = 2.2, p = 0.03) (Table r-to-z test. Note: there were no associations (r < 0.02) between the EoI and the frontal trend effect in either group (results not shown).Assessment of correlations between the EoI and the other AIs examined replicated our previous finding. ADHD subjects had a significantly weaker correlation between P8–P7 beta2 asymmetry and TP8–TP7 beta2 asymmetry (Fisher’s 3) Table . This waCognitive measures utilized in these secondary analyses cover several domains, such as: VWM, SWM, EFs, processing speed, attention, verbal phonologic ability, and motor dexterity Table .p = 0.025).The goal of these secondary analyses was to examine whether uncovered atypical EEG asymmetry in ADHD impacts cognitive functioning. However, before examining EEG-to-cognition associations, we first tested group differences in cognitive measures using the univariate procedure described above. Several group differences emerged Table . We did Regression analysis (described above) examined whether ADHD affection-status interacted with EEG asymmetry measures to predict ADHD cognitive characteristics. Several findings demonstrated a unique EEG asymmetry-to-cognition association pattern among ADHD subjects Table . Our prep = 0.00001) showing ADHD adults had increased rightward P8–P7 beta2 asymmetry during the CPT, and in post hoc analysis confirmed that this result was specific to the beta2 frequency band. We refer to this finding as our “EoI.” That study also found that while controls showed a robust positive correlation between beta2 asymmetry at the P8–P7 and the immediately anterior TP8–TP7 AI, ADHD subjects had no such effect. Lastly, this original study demonstrated a unique ADHD association between rightward P8–P7 beta2 asymmetry and fewer CPT commission errors.Our original study compared adult ADHD and control subjects’ EEG asymmetry during the Conners’ CPT in beta1 (12–16 Hz) and beta2 (16–21 Hz) frequency bands . That stp = 0.00003), again demonstrating that ADHD adults exhibit atypical rightward P8–P7 beta2 asymmetry during the CPT. Moreover, group differences at this inferior parietal index were again limited to the beta2 frequency band. We also replicated our previous finding showing that ADHD subjects exhibit a reduced correlation between beta2 asymmetry at the P8–P7 and TP8–TP7 AIs. We did not replicate our original finding showing that rightward P8–P7 beta2 asymmetry in ADHD was associated with fewer CPT commission errors.The current study sought to replicate and build upon these results using a larger ADHD sample. Expanded elements included: (a) testing additional frequency bands, (b) testing unilateral effects for all asymmetry findings, and (c) testing the association between ADHD abnormal asymmetry and a battery of cognitive tests. This current study replicated the EoI , and in additional bands for temporal–parietal , and superior-parietal (P4–P3: theta) indices. We also identified that three of five ADHD parietal beta asymmetry findings, including the EoI, were linked to greater unilateral right-sided beta power. Lastly, we uncovered multiple abnormal associations between rightward parietal asymmetry in ADHD and cognitive abilities.The nature of parietal brain function continues to be debated; however, some general themes have emerged. First, it has become increasingly clear that the complexity of the human parietal cortex mirrors that of the frontal lobes and plays key roles in many of the higher order operations traditionally ascribed to frontal brain regions –97. NextThis left–right dimensionality is evident across superior, inferior, and temporal–parietal regions. For example, the RH superior-parietal lobe (SPL) shows specialization for spatial orienting , while tContinuing this pattern of left–right specialization, the RH temporal–parietal junction (TPJ) has been associated with stimulus-driven attentional shifting , 104, whThe current study demonstrated abnormal increased rightward asymmetry in ADHD subjects across each of these parietal brain regions . This indicates that, during the CPT, ADHD subjects exhibit some form of increased weighting of right-lateralized brain regions previously associated with: orienting attention in space (RH SPL), sustained attention (RH IPL), and more flexible attention and cognitive sets (RH TPJ). The most robust and perhaps straightforward expression of this outcome is likely indicated by our beta2 findings.EEG beta has been associated with attention-directed information processing –75, 105,ADHD subjects exhibited rightward beta2 asymmetry in all parietal indices  with increased unilateral right-sided beta2 power evident for superior (P4) and inferior (P8) aspects. The relative weakness of the unilateral P8 effect when compared to P8–P7 asymmetry and the lack of unilateral effects in temporal–parietal regions indicates that rightward beta2 asymmetry is the critical metric within inferior and temporal–parietal brain regions. In contrast, the relative strength of the unilateral P4 effect versus P4–P3 asymmetry suggests that greater right-sided beta2 power is the critical metric within superior-parietal regions. Hence, we can refine our description of our findings to say that, during the CPT, ADHD subjects exhibited a relative increased weighting of RH versus LH contribution (as measured by rightward beta2 asymmetry) across inferior and temporal–parietal regions along with greater unilateral RH superior-parietal contribution (as measured by P4 beta2 power). Generally speaking, this pattern suggests some form of abnormal increased weighting of external-perceptual versus verbal-motoric processing across inferior and temporal–parietal brain regions with possible associated abnormalities involving the distribution of attention in space (the RH SPL effect).ADHD rightward EEG asymmetry was additionally evident in the theta band at the superior-parietal index (P4–P3), and in theta and beta1 bands at the temporal–parietal index (TP8–TP7). EEG theta has been implicated in the coordination of long-range cortical interactions and internally oriented brain functions such as working memory . The banfunctional asymmetry between brain regions thought to support attentional-state setting and applied attentional operations. Coordination of such mechanisms may be a key aspect of successful task-directed brain functioning  between beta2 asymmetry at the inferior (P8–P7) and temporal–parietal (TP8–TP7) AIs during the CPT. This demonstrates an ADHD reduced coordination of ctioning , 110 as Our analysis of EEG-to-cognition showed a pattern of abnormal reversed association between parietal asymmetry and cognitive abilities in ADHD. That is, where rightward asymmetry was associated with better or worse performance in ADHD subjects, an opposite pattern or non-effect was evident in controls. The majority of these findings indicated that rightward temporal–parietal asymmetry (across multiple frequencies) was associated with better VWM ability in ADHD, but worse VWM ability in controls. There were far fewer cognitive associations with superior (P4–P3: theta and beta2) and inferior (P8–P7: beta2) asymmetry. Asymmetry in these regions was exclusively associated with tasks that required constant attention to external visual stimuli, and for these sensory demanding tasks, ADHD subjects’ rightward superior and inferior parietal asymmetry was exclusively associated with worse performance.We previously discussed that increased RH TPJ activation occurs with flexible shifting attention. It has also been linked to the use of mental imagery. Greater activation of RH TPJ has been shown to occur during mental rotation tasks –114 inclAccording to this literature, the observed association between rightward TP8–TP7 asymmetry and better VWM ability in ADHD might reflect an ADHD default bias toward flexible attention and visual forms of cognition, which although maladaptive for the CPT, may bear advantages for tasks that benefit from mental imagery. ADHD subjects did exhibit better performance on the backward digit span task, which of the tasks utilized, is arguably the most likely to benefit from mental imagery. Moreover, in ADHD subjects only, rightward frontal beta2 asymmetry (F8–F7) was associated with better mental arithmetic, and our own and others’ previous work (described in the introduction) has indicated greater reliance on, or bias toward, visual cognition and sensory processing strategies in ADHD –15, 59.Finally, as noted, rightward superior (P4–P3) and inferior (P8–P7) parietal asymmetry in ADHD was exclusively associated with worse performance for tasks that required continuous attention to external visual stimuli and minimal internal computation. One interesting possibility is that poor task-regulation of RH TPJ function may create a circumstance, whereby ADHD individuals must continually reassert compensatory attention following task-disruptive attentional shifting during the CPT. If true, both rightward asymmetry at superior and inferior parietal indices, and their negative association to sensory weighted behavioral tasks, may reflect ADHD subjects’ attempting to regain their “attentional footing”  following task-disruptive attentional shifts.The current study replicated our previous finding showing that ADHD adults exhibit rightward inferior parietal (P8–P7) beta2 asymmetry during the CPT. Additional novel analyses established that this was part of a broader pattern of abnormal rightward beta2 asymmetry in superior (P4–P3), inferior (P8–P7), and temporal–parietal (TP8–TP7) regions, with additional frequency bands effects for the temporal–parietal  and superior-parietal (theta) indices. We also replicated our previous finding showing a reduced association between P8–P7 and TP8–TP7 beta2 asymmetry in ADHD. Finally, novel analyses indicated that rightward TP8–TP7 asymmetry in ADHD was associated with better VWM ability, while rightward P8–P7 and P4–P3 asymmetry was associated with worse performance for task requiring continuous attention to visual stimuli.In considering this pattern of results, we suggest a bipartite view of right biased parietal brain function in ADHD that highlights two semi-independent mechanisms, one linked to general state setting operations (RH TPJ), and one linked to applied attention during task-operations (RH IPL). We expect that ADHD individuals may exhibit variability in the primacy and strength of such effects, and/or with regards to their task-adaptive coordination. However, regardless of such variability, we expect that poor functioning and/or coordination of these mechanisms likely results in a convergent requirement for compensatory applied  attention during the CPT, which may explain the relative statistical robustness of the rightward P8–P7 beta2 asymmetry finding. This speculation also suggests that rightward P8–P7 beta2 asymmetry and possibly reduced coordination of P8–P7 and TP8–TP7 beta2 asymmetry may generally index poor task-directed brain function in ADHD  .The notion of abnormal functioning and/or coordination of both applied and state setting attentional operations in ADHD is well aligned with several recognized domains of ADHD pathology. For instance, abnormal norepinephrine (NE) function is implicated in ADHD , and topFurthermore, ADHD has been associated with abnormal network functioning , which implicates abnormal parietal brain function , 120. AlRightward parietal EEG asymmetry in ADHD is also well aligned with identified ADHD reduced posterior corpus callosum size , 128 andp = 0.00001) and full sample (p = 0.00003) and a pattern of rightward asymmetry was evident across all parietal findings, this effect was weaker in our intermediate sample alone . There are possible methodological reasons for this, such as unidentified variation in recruitment strategies, EEG time of day, and/or technician effects over the course of the study (approximately 3 years). However, it is also possible that variability in the strength of this effect portends key information.Although replication of our EoI was highly significant in our initial  –70, as wn-sizes, as was used in our current full sample. In short, we expect that the weaker rightward P8–P7 beta2 asymmetry uncovered in our intermediate ADHD sample may reflect natural variability associated with this effect. We also expect that such variability likely underlies the observed small-to-moderate effect sizes that were associated with the reported group differences in parietal asymmetry.The model also importantly suggests that rightward parietal asymmetry in ADHD is likely to manifest along a continuum of severity that reflects different classes of underlying causal mechanisms, i.e., from fixed modular deficits, to more subtle brain-state derived issues. The currently utilized CPT requires prolonged maintenance of a task-oriented state under conditions of low-reward and is perhaps well suited to capture ADHD asymmetry effects even in the face of such variability. However, optimal assessment of rightward parietal asymmetry in ADHD may generally require time-extended within subject assessment and/or large There are several additional limitations and/or circumstance that should be considered. First, all subjects in the current study, ADHD and controls, were the biological parents of children with ADHD. This bears the possibility that both groups may represent unique variants of adult ADHD and control samples. The ADHD group may reflect a particularly heritable ADHD variant, while controls may represent a unique group inclined to marry ADHD individuals and/or who are perhaps carriers of subclinical ADHD qualities. If the latter is true, this may have reduced our ability to detect group differences.Next, EEG involves multiple sources of measurement (electrodes) with each producing multiple data components , making the issue of multiple testing a central challenge. Researchers sometimes average signal across electrodes to limit the number of tests, but this sacrifices analytic resolution. Another approach, repeated measures ANOVA bears data loss issues as data must be available for each level of every included variable in order for a given subject’s data to be utilized, and because of channel and/or frequency specific EEG artifact this is a significant issue. Linear multilevel modeling can circumvent this problem; however, this approach was not utilized in the original study that we sought to replicate.a priori hypothesis of rightward parietal asymmetry in ADHD strongly limits this risk, and so we did not correct for multiple testing. Moreover, with the expanded analyses our primary goal was to identify coherent patterns of results (in EEG asymmetry and EEG asymmetry association to cognition), which also reduces the risk of type-1 error. In short, we acknowledge that without correcting for multiple testing our current results remain vulnerable to type-1 error. However, given the clear patterns within our current findings and their alignment with our earlier study results and our a priori hypothesis, we feel this possibility is remote.The original study used univariate ANOVA to test group differences in individual AIs, and due to our specific interest in replicating that study’s finding we used the same approach. This results in many analyses being performed increasing the risk of type-1 error. However, we judged that the highly targeted nature of our replication analyses and our specific Lastly, the original study required a current diagnosis of ADHD, whereas this study used a lifetime diagnosis. A lifetime diagnosis may include individuals who had childhood ADHD that waned as they grew into adults. In our current full sample, this represented 23 of 90 ADHD subjects . The decision to include ADHD individuals based on a lifetime diagnosis reflects a growing awareness that non-persistent ADHD may be an important variant form of adult-compensated rather than adult-remediated ADHD. That is, recent findings suggest that while some ADHD individuals grow to compensate for and/or experience diminished clinical symptoms, their brain functioning and cognitive abilities may continue to exhibit atypical ADHD-linked characteristics , 136. FuThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To the Editor: To investigate bats as potential reservoirs for Bartonella spp. in Vietnam, we screened a range of bat species to determine the prevalence and genetic diversity of Bartonella spp. in bat populations in southern Vietnam. In a study of bat biodiversity in southern Vietnam, 60 bats were trapped at 6 sites in Dong Nai Culture and Nature Reserve and Cat Tien National Park, Vietnam, in May 2013. Bats were trapped by using mist nets and harp traps set at ground level, and were euthanized by using isoflurane (http://www.avma.org/KB/Policies/Documents/euthanasia.pdf) for cataloguing at the Vietnam Academy of Sciences and Technology, Hanoi. Blood specimens were collected by cardiac puncture, and external measurements were recorded. Bats were speciated according to morphology (http://www.iucnredlist.org/).Bartonella spp. DNA by using primers specific for the citrate synthase A gene  of 44 compared with 1 (6.2%) of 16 fruit-eating bats . The prevalence of Bartonella spp. did not differ between sampling locations . Extracted nucleic acid was subjected to conventional PCR to detect lla spp. . Among iocations  or by eshttp://blast.ncbi.nlm.nih.gov/Blast.cgi) to assess sequence similarity. Potentially novel Bartonella phylogroups were identified as having <96% sequence similarity with all publicly available sequences in GenBank (Bartonella spp. and trimmed to the 327-nt region (positions 801–1127) commonly used for taxonomic classification (DNA sequences from the 21 PCR citrate synthase A gene amplicons (GenBank accession nos. KP100340–KP100360) were subjected to BLAST analysis (Bartonella phylogroups (I–X) among 21 Bartonella-positive blood samples from bats in Vietnam . Nine of these phylogroups showed <96% sequence similarity to all previously identified Bartonella sequences, suggesting they might belong to new Bartonella species. Bartonella spp. in Rhinolophus spp. bats were classified into phylogroups I, III, VIII, IX, and X. Phylogroups II and VII were detected in samples from Hipposideros spp. bats, and phylogroups IV and V were detected in Megaderma spp. bats. Phylogroup VI was detected only in a Megaerops spp. bat.Sequence analysis identified 10 distinct Hipposideros spp. bats and showed 96.3%–97.2% similarity to Bartonella spp. isolated from a bat fly found on a Hipposideros spp. host in Malaysia (GenBank accession no. JX416238). This similarity might suggest widespread distribution of this Bartonella spp. lineage in Hipposideros spp. bats or their ectoparasites in Southeast Asia. Additional genetic characterization of strains is needed to determine whether any of these novel phylogroups represent new species and to investigate their evolutionary and ecological relationships with other Bartonella spp. identified in Vietnam and elsewhere.Although 9 lineages  were novel, phylogroup II was identified in 4 Bartonella spp. (by DNA amplification) in bats in southern Vietnam at a prevalence of 35.0%, which is comparable with that reported in Kenya (30.2%) and Guatemala (33.0%) (The primary observation in this study was detection of  (33.0%)  . HBartonella spp., our findings indicate no increase in prevalence by age of bat, which would be expected if persistent infection were common. This finding, and detection of multiple lineages infecting individual bat species, may instead reflect high levels of transmission within and between bat species caused by crowded roosting areas and sharing of roosts by multiple species. This behavior provides opportunities for transmission of Bartonella bacteria or exchange of infected ectoparasites, such as Cyclopodia spp.  is included as an outgroup. Bootstrap support values are shown for nodes with >80% support. Taxa names for sequences determined in this study are indicated in bold italics, phylogroups are indicated in parentheses (I–X), and bat species are indicated after phylogroups.