Molecular diagnostic testing can identify these pathogens, including uncommon and previously undescribed species. Bartonella spp. infections, which are difficult to diagnose by using culture or serology. We analyzed clinical test results of PCR that targeted bacterial 16S rRNA hypervariable V1–V2 regions only or in parallel with PCR of Bartonella-specific ribC gene. We identified 430 clinical specimens infected with Bartonella spp. from 420 patients in the United States. Median patient age was 37 (range 1–79) years; 62% were male. We identified B. henselae in 77%, B. quintana in 13%, B. clarridgeiae in 1%, B. vinsonii in 1%, and B. washoensis in 1% of specimens. B. quintana was detected in 83% of cardiac specimens; B. henselae was detected in 34% of lymph node specimens. We detected novel or uncommon Bartonella spp. in 9 patients. Molecular diagnostic testing can identify Bartonella spp. infections, including uncommon and undescribed species, and might be particularly useful for patients who have culture-negative endocarditis or lymphadenitis.Molecular methods can enable rapid identification of  Bartonella spp. are fastidious, gram-negative intracellular bacteria that are transmitted to humans by insect vectors. The genus includes 12 species associated with human infection: B. henselae, B. quintana, B. bacilliformis, B. elizabethae, B. vinsonii, B. koehlerae, B. clarridgieae, B. alsatica, B. doshiae, B. grahamii, B. rattimassiliensis, and B. tribocorum , although infection can also cause hepatic lesions, ocular disease, osteomyelitis, and endocarditis ; seroprevalence in the PEH population is 5%–15%  or next-generation sequencing (NGS-16S) or performed a Bartonella henselae and B. quintana bi-species–targeted PCR (BT-PCR) requested by the ordering clinician. We included information for all patients who had an acceptable clinical specimen submitted to the University of Washington  Molecular Microbiology clinical diagnostic reference laboratory during 2003–2021. Acceptable specimen types were fresh frozen tissue, formalin-fixed paraffin embedded (FFPE) tissues, and body fluids other than blood. To identify Bartonella spp. as the final species assignment, had sufficient material for testing, and was an acceptable specimen type for the assay performed and if the presence of PCR inhibitors was excluded (inhibitors precluded ruling out Bartonella spp.). If a patient had multiple specimens submitted >30 days apart, we included only the information provided with the first positive specimen submission in the analysis. From the specimen submission form, we obtained the patient’s sex and age, US state and healthcare facility where the specimen was submitted, specimen collection date, and specimen description .We evaluated patient information if the specimen had The study was approved by the University of Washington Institutional Review Board . This study was reviewed in accordance with policies and procedures of the Centers for Disease Control and Prevention and was determined to be exempt from Institutional Review Board requirements.The University of Washington Molecular Microbiology laboratory performed all clinical testing pursuant to its high-complexity Clinical Laboratory Improvements Amendments license and College of American Pathologists accreditation. Laboratory-developed processes were validated in accordance with standards set by the Clinical Laboratory Standards Institute and monitored for quality through regular proficiency testing, biannual external inspections by the College of American Pathologists, and incorporation of control reactions as prescribed by the Clinical Laboratory Improvements Amendments.Bartonella spp. by BT-PCR incorporated broad-range 16S primers and 2 primer sets that amplified ribC alleles of B. quintana and B. henselae. The 16S primers also detect other Bartonella spp. but at a higher limit of detection: 100 templates per reaction for other Bartonella spp. compared with 5–25 for the Bartonella species-specific primers. We sequenced PCR products by using the Sanger method and assigned taxonomic classification after BLAST analysis (https://www.ncbi.nlm.nih.gov/refseq) records . For diagnostic reporting purposes, species with validly published names according to the taxonomic code were identified at the species level in the clinical diagnostic report; otherwise, we identified the genus in accordance with the laboratory’s standard operating procedures .2 tests to compare categorical variables and Mann-Whitney U tests to compare age distributions. For comparisons between patients who had B. quintana infections and those who had B. henselae infections, we excluded information from patients who had specimen results indicating another Bartonella sp. We performed all statistical analyses by using R software  and year of specimen submission for all BT-PCR assays, including those in which Bartonella spp. was not detected. Similar denominator data for PCR-16S and NGS-16S testing were not available.To examine the proportion of specimens infected with Bartonella spp. infection (Bartonella spp.), and both BT-PCR and PCR-16S sequencing on specimens from 121 (28%) patients. We detected Bartonella spp. DNA by both BT-PCR and NGS-16S in a specimen from 1 (<1%) patient and by BT-PCR, PCR-16S, and NGS-16S in a specimen from 1 (<1%) patient. We performed species-level identification for 272/272 (100%) specimens on which we performed BT-PCR, 163/265 (62%) specimens on which we performed PCR-16S sequencing, and 5/7 (71%) specimens on which we performed NGS-16S sequencing. Of 2,273 specimens submitted for BT-PCR during 2003–2021, we identified Bartonella spp. in 282 (12%) specimens from 272 patients.We identified 430 clinical specimens from 420 patients that had molecular evidence of nfection . We perfBartonella spp. in a higher proportion of specimens submitted as unfixed tissue  than those submitted as FFPE tissue . The total number of annual specimens submitted for BT-PCR testing increased over time; an annual median of 18 specimens during 2003–2012 increased to an annual median of 225 during 2013–2021  of specimens during 2013–2021; peak detection during this period occurred in 2019, when Bartonella spp. were detected in 17% of submitted specimens.We identified 013–2021 . OverallBartonella spp., we identified B. henselae in specimens from 338 (80%) patients, B. quintana from 54 (13%), B. clarridgeiae from 4 (1%), B. vinsonii from 2 (1%), and B. washoensis (GenBank accession no. ON402466) from 1 (1%). We identified Bartonella at the genus level in the remaining 21 (5%) patients; of those, we identified 2 candidate species through subsequent analysis: 1 case of endocarditis caused by Candidatus Bartonella mayotimonensis (Bartonella sp. (GenBank accession no. ON402515) (Bartonella sp. was identified in each patient.Among the 420 patients with detectable N402515)  Table. OBartonella spp. detected in >1 specimen and available data regarding their sex, 245 (62%) were male  were male compared with those who had detectable B. henselae . Age at the time of specimen collection was available for 415/420 (99%) patients; median age was 37 years (range 1–79 years). Most  patients were 18–65 years of age, 134/415 (32%) were <18 years of age, and 45/415 (11%) were >65 years of age. Patients who had detectable B. quintana in >1 specimen  were older than those who had detectable B. henselae .Among 397 patients who had ere male . A higheB. quintana more frequently in cardiac specimens  and B. henselae more frequently in lymph node specimens . We detected B. henselae in axillary , inguinal , and cervical  lymph node specimens and in cardiac , abscess , and liver  specimens. We detected B. washoensis in 1 lymph node specimen (unspecified anatomic location) and B. vinsonii (n = 2) and B. clarridgeiae (n = 4) only in cardiac specimens. For patients with Bartonella spp. identified in cardiac specimens, the aortic valve  was most frequently involved, followed by the mitral valve . We detected Bartonella spp. in >1 valve from 8 (6%) patients. Of cardiac specimens that had >1 valve affected, 105/116 (90%) were from the left side of the heart.Specimen descriptions were provided for all specimens. The most common specimens submitted were cardiac , lymph node biopsy or aspirate , and abscess fluid  . We idenBartonella spp. in cardiac tissue of male  than female  patients. However, 57 (38%) female patients had Bartonella spp. detected in lymph node specimens compared with 61 (25%) male patients, and 71 (47%) female patients had Bartonella spp. detected in other (not cardiac or lymph node) specimen types, compared with 77 (31%) male patients (p<0.0001)  or other noncardiac specimen types , whereas Bartonella spp. was most frequently identified in cardiac specimens from patients who were 18–65  and >65  years old (p<0.0001). For patients <18 years of age, B. henselae was the most commonly identified species .We observed a higher proportion of <0.0001) . For pat>10 patients in 8 (22%) states and for <5 patients in 16 states and the District of Columbia (46%). Among states with >10 specimens in which we identified Bartonella spp., California  and Washington  had the highest proportion of specimens infected with B. quintana; B. quintana was not identified in >10% of specimens in any other state.Information on the origin of specimens was available for 361/420 (86%) patients, representing 36 states and the District of Columbia . The staBartonella spp. infections. Those cases highlight the broad clinical spectrum of disease caused by Bartonella spp., provide evidence that multiple species can cause bartonellosis, and demonstrate the utility of clinical molecular testing for pathogen identification.We report 420 cases of bartonellosis in the United States identified by uniform, clinical molecular diagnostic methods at a single reference laboratory during 2003–2021, representing 36 US states and including 140 persons who had endocarditis because of B. henselae was the most frequently identified species causing bartonellosis. Although B. henselae was most often detected in lymph node specimens, consistent with cat-scratch disease  and FFPE (8%) tissue specimens highlight how preanalytical factors, such as formalin fixation, can limit assay yield. Other potential factors that can limit sensitivity of molecular methods include specimen selection, organism prevalence, and tissue volume. Formalin fixation damages DNA and can reduce assay sensitivity but has not always reduced positivity rates, perhaps because histopathologic evaluation permits selection of tissue most likely to contain microbial DNA (Bartonella spp. because they represented more severe illness, and submitted specimens were primarily from tissues known to be infected by those pathogens. Second, the specimens did not represent a random sample of persons with bartonellosis; therefore, we could not estimate incidence or perform statistical inference testing. Third, not all geographic regions or states were equally represented, limiting our ability to compare results between different geographic areas. Fourth, we had little information regarding clinical features of the patients from whom specimens were collected, limiting our ability to determine potential risk factors on the basis of medical or social history. Fifth, preanalytical specimen handling can affect diagnostic yield; we could not assess or control variations in storage or transport conditions or tissue processing, such as formalin pH or acid-based decalcification of bone. Sixth, clinical testing might have missed Bartonella spp. other than B. henselae or B. quintana that were present at levels below the limit of detection for the 16S primers, because the ribC primers were designed to increase specificity and sensitivity for detecting B. henselae and B. quintana. Finally, some specimens might have been misclassified, leading to a higher proportion of specimens categorized as abscesses or tissue if more specific information on anatomic site was not provided on the specimen submission form.The first limitation of our study is that the analyzed specimens were not representative of all infections caused by Bartonella spp. Those methods should be considered for patients who have culture-negative endocarditis or lymphadenitis of unclear etiology, particularly in persons with established risk factors, including exposure to cats or prior homelessness. Broader use of molecular methods in suspected cases of bartonellosis will help elucidate the full clinical spectrum of Bartonella infections and increase awareness of this underrecognized pathogen.In conclusion, molecular methods provide a powerful diagnostic tool to detect infections caused by Bartonella spp. infections identified by molecular methods, United States.Additional information for


Poor sleep quality has been reported among adults with attention-deficit hyperactive disorder (ADHD) and has been associated with reduced sensory-processing abilities and low work performance. However, the relationships among sleep quality, sensory processing and the insufficient work performance of adults with ADHD is still unclear.Following the World Health Organization’s international classification of functioning, disability and health concepts, this study compares sleep quality and sensory processing (body functions) and work performance (participation) of adults with ADHD to those of controls, and examines the relationships among those components in adults with ADHD.Participants were 69 adults with ADHD and 52 age- and gender-matched controls. All completed a sociodemographic questionnaire, the Mini Sleep Questionnaire, the Adult/Adolescent Sensory Profile and the Occupational Questionnaire.Compared to controls, the adults with ADHD showed significantly poorer body functions  and lower work performance. Significant correlations were found between sleep quality and sensory-processing abilities and between sleep quality and work performance among adults with ADHD. Regression analysis revealed that for adults with ADHD, sleep quality accounted for 22.0%, and sensory sensitivity accounted for 10.9%, of the variance of their work performance.Sleep quality, together with sensory processing patterns, has a significant influence on work performance of adults with ADHD. Because work is a vital occupation for adults, these body functions need to be considered in clinical settings, and further research on this topic is required for better understanding of the phenomena.ADHD add Sleep quality add work performance add sensory processing


Over the past decade, researchers have been seeking to understand the consequences of adult attention-deficit/hyperactivity disorder (ADHD) for different types of everyday behaviors. In this study, we investigated the associations between ADHD and political participation and attitudes, as ADHD may impede their active participation in the polity.This observational study used data from an online panel studying the adult Jewish population in Israel, collected prior the national elections of April 2019 (N = 1369). ADHD symptoms were assessed using the 6-item Adult ADHD Self-Report (ASRS-6). Political participation , news consumption habits, and attitudinal measures were assessed using structured questionnaires. Multivariate linear regression analyses were conducted to analyze the association between ADHD symptoms (ASRS score <17) and reported political participation and attitudes.200 respondents (14.6%) screened positive for ADHD based on the ASRS-6. Our findings show that individuals with ADHD are more likely to participate in politics than individuals without ADHD symptoms . However, participants with ADHD are more likely to be passive consumers of news, waiting for current political news to reach them instead of actively searching for it . They are also more prone to support the idea of silencing other opinions . The findings hold when controlling for age, sex, level of education, income, political orientation, religiosity, and stimulant therapy for ADHD symptoms.Overall, we find evidence that individuals with ADHD display a unique pattern of political activity, including greater participation and less tolerance of others’ views, but not necessarily showing greater active interest in politics. Our findings add to a growing body of literature that examines the impact of ADHD on different types of everyday behaviors. Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric syndrome characterized by marked lack of attention and/or hyperactivity and impulsiveness . These sPolitical participation—the voluntary actions engaged in by members of the public in the political arena—is considered a cornerstone of functioning democracies, enabling nonprofessionals-citizens to influence public policy and the elected officials who shape those policies . TraditiThe association between ADHD and political participation deserves more attention both because it is a relatively common condition and because of its distinctive characteristics . SeveralAnother known predictor of political participation that can be relevant for ADHD symptoms is political interest –35. It iAttentiveness to various political messages in the competitive environment of the political domain raises questions regarding the views of individuals with ADHD on tolerance to multiple opinions and voices in the political sphere. This matter is particularly important since it might conflict with one of democracy’s fundamental qualities—freedom of speech. Hence, an interesting question we can address in our analysis is whether ADHD is associated with intolerance towards freedom of speech and to what extent it reflects on other democratic norms. Lastly, some evidence indicates that individuals with ADHD might show less trust in governmental institutions. For example, Dvorsky et al. (2022) show that lower COVID-19 vaccination willingness and trust were correlated with ADHD among adolescents . As a goThe current study is based on a 5-wave online panel study, with a sample representative of the adult Jewish population in Israel. Data for the larger project were collected between January and April 2019, before and after the national elections held on April 9 of that year. The relevant data for this study were gathered in three waves between January 28 and March 29, 2019. Most of the measures were collected during the first wave. News-gathering habits were reported in the second wave. Two measures—symptoms of ADHD and (curbs on) freedom of speech—were reported in the third wave. In case a measurement was collected over more than one wave, we included in our data the first time the question was presented to the participants . To assure that our panel is representative of the general population, participants were recruited from the overall iPanel pool based on demographic quotas that approximate these same demographics among the general Israeli population. These included gender, age, geographical location, education, religiosity, and income. As in most recent political studies –39, the To assess the presence of adult ADHD symptoms, we employed the widely used Adult Self-Report Scale (ASRS) screening tool . StudiesTraditional political participation. Following similar studies that examined political participation  and the possibility of new elections”; “There are times when it seems better to deviate from the rules of the democratic game in order to achieve significant change.” A composite index was created by averaging responses to the two items .Political orientation. Respondents were asked to place themselves on a political orientation scale ranging from 1 to 7, where 1 indicates the extreme right and 7 the extreme left . .Trust in political institutions. In three items, participants reported their level of trust in the government, parliament, and politicians on a scale from 1  to 5 (very high level of trust). Responses were averaged to create a composite index .Political interest. In four items, participants were asked to report on a scale of 1 (strongly disagree) to 5 (strongly agree) their level of interest in politics . A composite index was created by averaging responses to the four items . The full wording of all measures can be found in the Online Appendix.Covariates. To test whether ADHD symptoms affect political participation and attitudes above and beyond other potential explanations, we controlled for other known factors. These include sex, age, level of education, level of income, religiosity, and stimulant therapy. As political orientation and interest are also known factors of political participation, we controlled for them as well. Lastly, we controlled for participants’ political knowledge. To measure political knowledge participants were presented three questions concerning current affairs. The scale ranged from 0  to 3 .We first examined the association between ADHD symptoms and our outcome variables by comparing the dichotomous non-ADHD and ADHD groups . Differences in proportions between ADHD and non-ADHD individuals were assessed using Pearson’s chi-square analysis. Next, we divided participants into five groups according to their ASRS-6 scores and tested whether a higher ASRS score is associated with specific political behaviors and attitudes. As a third test, we reran all analyses comparing two groups of respondents: those who scored above 17 in the ASRS-6 but were not taking prescribed ADHD medication; and all respondents who were taking such medication, regardless of their ASRS-6 scores. Finally, to test whether having ADHD symptoms is correlated with political behavior and attitudes above and beyond other factors that might influence the latter, we ran a multivariate linear regression analysis controlling for the following variables: age, sex, level of education, level of income, religiosity, political orientation, political interest, political knowledge, and stimulant therapy. All analyses were conducted using SPSS , Version V25 . The level of statistical significance was set at p < .05.χ2 = 29.41(4), p < .001) and income (χ2 = 20.63(4), p < .001) were correlated with ADHD, while sex, education, religiosity, and political orientation were not (ps > .119).A sample of 1,374 participants was recruited for this study. Of these, 1369 panelists completed the relevant questionnaires, 44.0% of whom were female. Two hundred (14.6%) subjects screened positive on the ASRS  and were coded as having symptoms of ADHD. While this number is higher than identified in the adult population (estimates range from 1% to 7.3%) , we belit(1013) = 2.781, p = .006, Cohen’s d = .292) and in traditional ways, t(1367) = 3.077, p = .002, Cohen’s d = .235. At the same time, participants with ADHD had a greater tendency to be passive consumers of news—i.e., waiting for political news to find them rather than actively seeking it out, t(1364) = 2.922, p = .004, Cohen’s d = .224. Respondents with ADHD were also less tolerant towards others voicing their opinions, t(1367) = 2.004, p = .045, Cohen’s d = .153. We did not observe a significant difference between participants with vs. without ADHD in their sense of representation, willingness to curb democratic norms, trust in political institutions, general interest in politics, or consumption of popular news media. We categorized participants dichotomously as screening positive or negative for ADHD based on the widely accepted cutoff score of 17 . HoweverOur third set of analyses compared respondents who screened positive for ADHD in our study but were not taking stimulant drugs to treat their symptoms (N = 179), and all respondents who reported taking stimulants regardless of their ASRS-6 scores (N = 52). Several pharmacological agents are used for the treatment of ADHD. Those therapies attempt to reduce the symptoms of patients and to improve their function. We attempted to evaluate whether the use of such medications is associated with different political participation patterns in subjects who present ADHD symptoms. The results showed no significant differences between the two groups in any parameter except trust in political institutions see .Finally, we ran a set of multiple regression analyses to test the relationship between ADHD symptoms and political behaviors and attitudes while controlling for various factors, including age, sex, education, income, religiosity, political orientation, and use of stimulant drugs. Education, income, religiosity, and age group variables were dummy coded before being added to the regression.Multivariate regressions confirmed the associations found in the t-tests regarding political behaviors and attitudes see . SpecifiPrevious work suggests that genetic and biological factors might help explain some political behaviors –55, 59. Additionally, participants with ADHD symptoms were found to be less tolerant of other people’s views. Considering that participants with ADHD symptoms were not more likely to curb democratic norms as a whole, this might reflect their attentiveness rather than a broader democratic issue.To the best of our knowledge, the impact of ADHD on political behavior has not previously been evaluated. However, a recent study has addressed the use of social media among patients with ADHD. Social media users with ADHD were found to be less agreeable, to post more often, and to use more negations, hedging, and swear words. ADHD is also correlated with addictive social media use . Social Impatience and intolerance towards the opinion of others and/or willingness to interrupt others while speaking are also symptomatic of ADHD as defined by the DSM-V . Our finWhile there was no difference between the ADHD and non-ADHD groups in regard to the amount of political content they consume via popular news outlets, we found that participants with ADHD are more prone to consume news passively, waiting for it to “find them.” This implies, in turn, that these individuals tend to base their current political knowledge on information that is screened for them by others, or that is filtered and curated by social media algorithms. This finding, which was not previously reported, may have implications for how patients with ADHD perceive reality and their vulnerability to being captured by information bubbles.Participants who were treated by stimulants did not differ from non-treated ADHD-positive participants in our study. A possible explanation for this finding is that pharmacological treatments for ADHD affect symptoms over a limited timeframe, even when long-acting agents are used. ADHD patients tend to take their medication in the morning, so as to manage their symptoms during working hours. However, they are more likely to post on social media at night . As suchOur study has four main limitations: First, it was performed on a small population in one specific political context . It is, therefore, difficult to draw general conclusions regarding other countries. At the same time, attention disorders are common worldwide, and we hope that further research will this matter in other countries. Second, this study used a screening tool rather than a clinical diagnosis. Third, it is possible that individuals with ADHD will demonstrate a different pattern of responding to surveys. For example, they might lose interest in the middle of filing the survey, depending on the time of day. As no previous literature on this matter exists, our research was carried out using the conventional method without special adjustment for attention disorders. Forth, it examined political participation through self-reports.Nonetheless, our findings provide insights into the possible effects of ADHD on political behavior. With growing recognition of the existence and impact of ADHD among adults, the effects of the disorder on all aspects of human life are beginning to unfold. Considering that political participation entails voluntary actions taken by individuals to influence public policy and those elected officials who shape those policies, and given that ADHD is correlated with weakened populations, it is important to understand both whether the voices of those with ADHD are heard, and how this segment of society affects the polity.More broadly, as our understanding and acceptance of neurodiversity grows , we needS1 Appendix(DOCX)Click here for additional data file.S2 Appendix(DOCX)Click here for additional data file.S3 Appendix(DOCX)Click here for additional data file.S1 File(SPS)Click here for additional data file.S2 File(ZSAV)Click here for additional data file.


Parental management has an important role in preventing problematic smartphone use among adolescents with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine the parental factors  and adolescent factors  related to parental efficacy in managing adolescent smartphone use (PEMASU) among 237 parents of adolescents with ADHD. PEMASU was measured by the Parental Smartphone Use Management Scale. Parental depressive symptoms and parenting styles  were measured by the Center for Epidemiologic Studies—Depression Scale and Parental Bonding Instrument, respectively. Adolescent ADHD and ODD symptoms and problematic smartphone use were measured by the Swanson, Nolan, and Pelham, version IV scale and Problematic Smartphone Use Questionnaire, respectively. Three models of hierarchical linear regression were performed to examine the parental and adolescent factors related to PEMASU. The results indicated that adolescent older age and more severe ODD symptoms and problematic smartphone use were significantly associated with lower PEMASU, whereas greater parental affection/care was significantly associated with higher PEMASU. This study demonstrated that both parental and adolescent factors contribute to PEMASU among parents of adolescents with ADHD. Intervention programs aiming to enhancing PEMASU need to take these related factors into consideration. Problematic smartphone use (or smartphone addiction) is common among adolescents with ADHD. A study conducted in 4512 South Korean adolescents demonstrated that ADHD symptoms were the most significant factor related to the severity of problematic smartphone use ,4,5. LonThe studies examining family factors of problematic smartphone use in adolescents are scarce . PreviouParental efficacy in managing adolescent smartphone use (PEMASU) may affect whether parents can successfully carry out the management for adolescent problematic smartphone use; however, this has not been discussed in depth in the literature. Overall parental efficacy refers to the belief and confidence the parents have in their competence to successfully execute parenting behaviors and foster children’s positive development . ParentsSituation-specific parental efficacy refers to parents’ belief and confidence the parents have in their competence to ensure children’s attainments of some specific tasks in their daily lives ; for exaFactors that relate to PEMASU in parents of adolescents with ADHD have not been surveyed. As observed in the socioecological model , both adThrough this study, we aimed to examine the associations of parental factors  and adolescent factors  with PEMASU in parents of adolescents with ADHD. We hypothesized that more severe adolescent problematic smartphone use, adolescent ADHD and ODD symptoms and parental depression, and greater overprotective parenting style were significantly associated with lower PEMASU in parents of adolescents with ADHD, whereas a democratic parenting style was significantly associated with higher PEMASU.The methods of recruiting participants have been described elsewhere . In brieTwo child psychiatrists (WJC and CFY) confirmed the eligibility of 237 potential participants, and 231 (97.5%) parents agreed to participate. Regarding the demographics of participants, 192 were mothers and 39 were fathers; mean age was 43.8 years (standard deviation [SD] = 6.1 years); mean number of years of academic education completed was 13.8 years (SD = 2.8 years). Regarding the demographics of adolescents with ADHD, 32 were girls and 199 were boys; mean age was 13.7 years (SD = 1.8 years); 190 were in a two-parent family.All participants provided written informed consent. Trained research assistants explained to the participants how to complete the research questionnaires and assured that their responses would be confidential. Participants completed the research questionnaires in the interview rooms of the psychiatric outpatient units individually and could seek help from the research assistants if they experienced difficulties in completing the questionnaire. The Institutional Review Board of Kaohsiung Medical University approved the study .no efficacy at all) to 6 (extremely strong efficacy). Participants who rated a higher mean score had a higher level of PEMASU. A previous study on parents of adolescents with ADHD supported that the PSUMS had acceptable reliability and validity [The PSUMS contained 17 items assessing the 3 dimensions of PEMASU  in the previous one month . Particivalidity . The intnot at all) to 3 (very much). Participants who rated a higher mean score had the children with more severe ADHD and ODD symptoms. Previous studies have confirmed that the C-SNAP-IV had acceptable reliability and validity [The C-SNAP-IV–parent form contained 26 items assessing children’s inattention (9 items), hyperactivity/impulsivity (9 items) and ODD symptoms (8 items) in the previous one month ,41. Partvalidity . The intvery unlikely) to 4 (very likely). Participants who rated a higher mean score had the children with more severe problematic smartphone use. A previous study demonstrated that the PSUQ had acceptable psychometric propensities [The PSUQ contained 8 items assessing the severity of children’s problematic smartphone use in the previous one month . Particiensities .never) to 3 . A previous study found that the M-CES-D had acceptable psychometric propensities [The M-CES-D contained 20 items assessing the frequency of parental depressive symptoms in the previous one month ,44. Partensities . The intvery likely) to 4 (very unlikely). Participants who rated a higher mean score on the parental affection/care and overprotection dimensions had greater affectionate and warm parenting behaviors and denial of adolescent psychological autonomy with discouragement of adolescent behavioral freedom, respectively. A previous study found that the C-PBI has acceptable reliability and validity [The C-PBI contained 25 items assessing 2 dimensions of long-term parenting behaviors  ,45. Partvalidity . The int2 was included in determining the percentage of variance explained by each model.Categorical and continuous variables were first analyzed using frequency (percentage) and mean (SD), respectively. The correlations among the variables were examined using Pearson correlation analyses. Three models of hierarchical linear regression were used to test the associations of parental and adolescent factors with PEMASU. The 3 sets of independent variables were demographic variables , adolescent factors (adolescent ADHD and ODD symptoms and problematic smartphone use), and parental factors . Parents’ age was not considered in the analysis because of its significant relationships with other demographic variables. The adjusted RThe results of descriptive statistics and correlation coefficients for the variables are presented in The results of three hierarchical linear regression models examining the associations of parental and adolescent factors with PEMASU are shown in The present study demonstrated that the severities of ODD symptoms and problematic smartphone use in adolescents with ADHD were negatively associated with PEMASU. Core ODD symptoms include anger, irritable mood, argumentativeness, defiance, and vindictiveness . AdolescAdolescents who have problematic smartphone use may increase the time spent on using smartphone to achieve satisfaction ,29, becoThe present study found that older age of adolescents was associated with lower PEMASU; however, the effect of age became nonsignificant when the effects of ODD symptoms and problematic smartphone use were considered. Presentations of ODD symptoms and problematic smartphone use may become more severe and intense as adolescents grow up. This study did not discover significant associations of inattention and hyperactivity/impulsivity with PEMASU. The participants in this study were invited from clinical units; therefore, their children received pharmacological and/or behavioral treatment for ADHD. ADHD symptoms might be alleviated.The present study demonstrated that a parenting style of more affection/care was significantly associated with greater PEMASU in parents of adolescents with ADHD. Affectionate and caring parenting behaviors can result in good parent–child interaction  that canTo the best of our knowledge, this study is the first to examine the parental and adolescent factors related to PEMASU among parents of adolescents with ADHD. However, we collected the data based on the parents’ self-report; therefore, there might be single-rater bias. Future studies should collect data from adolescents and not only from parents to reduce the single-rater bias. Second, this cross-sectional study could not make the inference in the temporal relationships between the related factors and PEMASU. Further prospective studies are needed to examine the temporal relationships. Third, the participants were recruited from outpatient clinic units. The source of participants limited the generalization of the results found in this study to parents and ADHD adolescents who have not visited clinic units.The association between ADHD symptoms and PEMASU should also be investigated in the population of ADHD adolescents who have not visited a clinical unit. Several models of behavioral treatment for ODD problems have been proposed for adolescents with ADHD ,49. WhetThe present study identified that ADHD adolescents’ ODD symptoms and problematic smartphone use were negatively associated with PEMASU, whereas parental affection/care was positively associated with PEMASU in parents of adolescents with ADHD. The results indicate that both parental and adolescent factors correlated with PEMASU in parents of adolescents with ADHD. The present study highlights the need for family-based interventions but not only focusing on adolescents for problematic smartphone use in adolescents with ADHD. Provision of parenting resources to enhance PEMASU and affectionate and caring parenting is warranted to increase PEMASU among parents of adolescents with ADHD and reduce the risk of adolescent problematic smartphone use in this digital age.


Motivation is what moves us to act, what engages us in goal-directed behavior. The Self Determination Theory (SDT) is a motivational framework conceptualizing motivation—or internal motives—as a continuum of motivation qualities fueled by satisfaction of the three basic psychological needs Autonomy, Relatedness, and Competence. ADHD has been associated with motivational alterations that contribute to academic difficulties. However, ADHD theories and research are mainly focused on the effects of reinforcement on behavior, with little attention for the broader definition of motivation, that is, internal motives. Therefore, the main objective here was to introduce the SDT as theoretical framework within which we can develop relevant research questions about motivation in the field of ADHD.To this end, we (i) present the SDT as a comprehensive motivational framework, and (ii) describe current motivation-related ADHD theories and research.Based on this, we suggest how SDT can be used as a guiding framework in generating relevant research questions that can help broaden our understanding of the role motivation plays in individuals with ADHD.We conclude that ADHD research on motivation would benefit from (i) including internal motives as potential key mediators in the relation between environmental factors and behavior/symptoms; (ii) studying potential negative effects of external reinforcers intrinsic motivation, affect, and well-being. Finally, we conclude that this framework carries value for further development of clinical interventions for those with ADHD. These ier time) . For exa’s needs   introduce the SDT in more detail, (ii) describe current motivation-related ADHD theories and research in more detail, and then (iii) outline how SDT can be used as a guiding framework in suggesting research questions that can help broaden our understanding of the role motivation plays in individuals with ADHD.SDT is a macro theory of motivation that is built up from five dissociable mini-theories developed and integrated over time . These mA-motivation, this is non-intentional behavior arising from (i) the idea that behavior is not linked with perceived contingency, (ii) feeling incapable to perform the behavior, or (iii) a lack of valuation of the activity  will facilitate the innate drive toward growth as compared to goals that thwart these needs  intrinsic motivation , (ii) internalization of drives , (iii) experienced basic need satisfaction/frustration, and (iv) pursuit of intrinsic goals. These internal motives mediate the relationship between the context on the one hand, and motivated behavior and a variety of life outcomes on the other hand . Extensing e.g., , 2015. Aimplicitly include internal motives. Below, the most prominent ADHD theories that touch on motivation will be briefly explained, and situated on the different levels of Reeve’s motivation model  an altered sensitivity to reward and/or punishment  and (ii)d action   thed action , and (3)d action , 2005.Internal motives that mediate the relation between External triggers and Motivated action  result in attempts to escape such delays when possible (Motivated action), and in strategies to distract from these negative emotions when escaping is not possible (Motivated action)  see .Motivated action) and not the negative emotions experienced during waiting . One strand of studies supporting this model focuses on the increased preference/choice for small immediate rewards over larger delayed rewards in individuals with ADHD compared to their typically developing peers. More specifically, these studies show consistently and strongly (with a medium effect size) that individuals with ADHD, when presented with choices between smaller immediate and larger delayed rewards, choose the smaller immediate rewards more often than individuals without ADHD . Similarly, but more specifically focused on the executive function Inhibitory Control, Secondly, Motivated action  research has shown that compared to typically developing peers, individuals with ADHD demonstrate a medium-sized reduction in striatum activation when anticipating money that is offered contingent on performance  could be a first step. A first hypothesis might be that ADHD symptoms and related difficulties such as EF dysfunctions and externalizing problems might elicit a more controlling style from the teacher . What the causal direction of this relation is, will need to be the focus of future research. Likely, there is a bidirectional relation that dynamically develops over time. Moreover, if ADHD is indeed associated with decreased basic need satisfaction, ways in which the basic needs of individuals with ADHD can be effectively supported by their parents and teachers should be assessed as well, and this may have implications for interventions (see below).It is an empirical question whether individuals with ADHD prefer different goals than individuals without ADHD. May extrinsic goals—such as wealth and fame—be preferred over intrinsic ones—such as self-acceptance, affiliation, and community contribution—to a larger degree in those with ADHD as compared to typically developing individuals? And would (the pursuit of) the experience of self-acceptance, affiliation, and community contribution be associated with decreased externalizing behavior in individuals with ADHD?Of particular interest may be to study motivation of individuals with ADHD not only in the academic domain, but across life domains. Motivation in the academic domain has been studied extensively. An influential review of We believe it is unlikely that individuals with ADHD would have low intrinsic motivation in general, across life domains and contexts. It seems more probable that individuals with ADHD, like individuals without ADHD, will experience high intrinsic motivation for certain activities and low intrinsic motivation for others. For example, Moreover, longitudinal studies can elucidate if children and adolescents with ADHD experience a developmental delay in goal directed behaviors. Finally, the association between motivation and goal-directed behavior may also be reversed, with goal-directed behavior potentially having an influence on motivation. For example, As some groups of individuals possess an orientation toward more autonomous or controlled regulation strategies , it mighThe focus on external reinforcement to promote desired behaviors might come with potential costs to performance quality, motivation quality, affect, and well-being. The undermining effect of extrinsic reinforcers on intrinsic motivation has been demonstrated in typically developing individuals particularly under certain circumstances such as when the reinforcer is experienced as controlling rather than as informative, and when the motivation quality for that task or activity is reasonably high to begin with . HoweverHowever, the studies included in these reviews consistently rely on typical cognitive laboratory tasks such as arithmetic tasks, continuous performance tests, paired associate memory tasks, repetitive motor tasks, executive functions tasks , and useAdditionally, SDT-focused experiments, as opposed to ADHD studies, typically take into account a range of task-related outcomes besides post-task behavioral persistence, such as performance quality , level of intrinsic motivation, affect, and state well-being during and after the task. All of these seem to decrease when extrinsic incentives are included in the research design . TherefoInternal motives, that is motivation quality and underlying basic need satisfaction, mediate the effect of External triggers such as parental support on Motivated action and Life outcomes  makes use of choice paradigms in which participants choose between smaller immediate rewards and larger delayed ones. Adding measures of individuals’ experiences during waiting such as skin conductance, heart rate, pupil dilation, and subjective ratings, will help gaining insight into internal motives. Specifically, Douglas’ early work showed that behavior/performance of individuals with ADHD significantly improves when tasks are made to be more salient, novel, interesting, or stimulating . While thow this reduced activation is linked to ADHD symptoms  are consistently associated with ADHD symptoms (see for a meta-analysis Internal motives, the “missing link” between environment and behavior (see Moreover, in the research of vior see . Such meA number of specific SDT-based interventions have been developed but not tested in an ADHD population (see for some recent e.g., internal motives including motivation quality and basic need satisfaction as potential key mediators in the relation between environmental factors on the one hand and behavior or symptoms on the other. Also, we have suggested to study potential negative effects of external reinforcers applied in situation of high intrinsic motivation, on outcome measures such as intrinsic motivation, affect, and well-being. Finally, we believe that this framework also carries value for further development of clinical interventions for those with ADHD, such as the SDT-based Autonomy Support Intervention Program. Our hope is that this overview will stimulate future research, so that we will better and more fully understand which role motivation plays in individuals with ADHD, and which circumstances are optimal for individuals with ADHD to feel supported in their basic needs, and to experience autonomous qualities of motivation.In sum, we suggest that SDT is a useful framework for the field of ADHD, and new research on motivation can be embedded in this framework. Specifically, we have proposed to extend current research to add


ADHD is a condition with extensively researched increased risks of psychiatric disorders, traumatic injury, impulsivity, and delayed response times.To analyze the incidences of fractures in patients with ADHD on various medication regimens.Using the TriNetX database, we created seven patient cohorts, all of age under 25, based on medication types commonly used for ADHD. The cohorts we created were: no medication use, exclusive use of a -phenidate class stimulant, exclusive use of an amphetamine class stimulant, nonexclusive use of formations of either stimulant, exclusive use of non-stimulant medications approved for ADHD, nonexclusive use, and no medications. We then examined rates while controlling for age, sex, race, and ethnicity.The comparison of ADHD to neurotypical individuals revealed an increased risk for all fracture types. For the controlled analysis, all but one cohort had significant differences in each fracture type compared to the baseline cohort of ADHD patients without any medication use. Patients in the “phenidate” cohort had an insignificant difference in risk of lower limb fractures. Patients in the “any medication,” “-etamine,” “stimulant,” and “not ADHD” groups all had significant decreased risks for all fracture types, with confidence intervals often overlapping between treatment modalities.As patients experiment with different medication regimens, providers should be aware of the difference in risk of fracture by medication type. Our results highlight the need for continued research to better discern appropriate medication regimens with the goal of improving overall risk reduction and producing better outcomes for individuals with ADHD. Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common developmental disorders, affecting up to 10% of the population . The group with ADHD is the “Overall ADHD” group, and the group without ADHD was labelled the “Neurotypical” group. We then created six subgroups within the ADHD group based on medication regimen, which can be understood as three cohorts of nonexclusive medication use and three cohorts of exclusive medication use: the “no meds” cohort had never taken an FDA-approved ADHD medication ; the “anThe events of interest in this study were identified as follows: “central fractures,” consisting of fractures of the skull, face, cervical vertebrae, spine, ribs, or pelvis ; “upper limb fractures,” consisting of fractures of the shoulder, humerus, forearm, wrist, or hand ; “lower limb fractures,” consisting of fractures of the femur, lower leg, ankle, or foot ; or “any fractures,” consisting of any prior mentioned fracture type.We performed two sets of analysis using the TriNetX statistical software. First, we established the overall prevalence of our events by comparing the base rate of each fracture type within the large ADHD group to the “neurotypical” or not ADHD group. The results of this set of analysis are presented in t-test values for these characteristics, are presented for each sub-group in Following this analysis, we sought to isolate the effect of ADHD medications on fracture rates. We established the “no medication” ADHD group as the baseline, as they have the neurobiology of ADHD without any medication effects. We then balanced each ADHD subgroup to this baseline cohort based on age, sex, race, and ethnicity using nearest-neighbor matching to a difference between propensity scores <0.1 . The idep-value <0.05. As this study contained only deidentified aggregate data, the Colorado Multiple Institutional Review Board (COMIRB) designated it as non-human research not in need of approval.Once the cohorts were balanced, event rates were extracted from the relevant patient records, and odds ratios with 95% confidence intervals were calculated from the given incidence of each event. Risk reduction was calculated as the risk of event in the baseline group minus the risk of event in the comparison group. The baseline event rate for the “no meds” is not provided, as the individuals analyzed varied based on matching to the relevant medication sub-group. The results of this set of analysis are collected in The original size of each cohort is included in After matching, the cohort size for each event varied from 668 to 13,223. All but one cohort had a significant difference in each fracture type, with all differences being reduced from the baseline, which was the cohort of ADHD patients without any medication use. Patients in the “phenidate” cohort had an insignificant difference in risk of lower limb fractures. Patients in the “any medication,” “-etamine,” “stimulant,” and “not ADHD” groups all had significant decreased risks for all fracture types; detailed results are in In our uncontrolled analysis between neurotypical individuals and all individuals with ADHD, all fracture outcomes occurred more commonly in the ADHD cohort. This replicates an important observation, and likely contributes to the higher rates of injuries in many aspects of ADHD, including traumatic and athletic injuries , 11. ComThe neurobiology of ADHD seems to affect nearly all aspects of health . While sThere are many available treatments for ADHD, and more are approved every year. For young children, the first line treatment is behavioral intervention on the part of the parents, rather than medications . In oldeMany patients, parents, and providers are concerned over the potential side effects of medication types. Within stimulants, methylphenidate is known to decrease the bone density with chronic use in both animal models and human studies , 20. ThiWhile both stimulants and non-stimulants are known to impact behavior, stimulant medications have more frequently been the focus of research. Behavioral changes associated with stimulant medications are known to decrease the chance of fracture in patients with ADHD . Our datOur study is not without limitations. As with all studies involving deidentified, aggregate data, we were unable to trace individuals throughout time or multiple simultaneous events; for example, a patient who fractured their skull, humerus, and femur in the same incident would be present once in each event analysis, while someone who fractured their humerus and repeatedly presented to medical care for pain medication would be present in the data one time for each visit. Furthermore, we did not separate out different types of fracture such as pathological, stress, or traumatic, which may have presented different data. Additionally, we did not directly compare amphetamines and methylphenidates, although substantial differences between amphetamines and methylphenidate medications are recognized in the literature, with amphetamines often having longer effects . While aThis study offers new information that may aid providers in providing information to patients and families regarding the impact of ADHD treatment on bone health. As patients experiment with different medication regimens, providers should be aware of the difference in risk of bone fracture by medication type. Furthermore, our manuscript is the first to directly compare fracture risks in non-stimulant and stimulant medications, finding intriguing differences across medication types that cannot be understood at a causal level from the available data. However, by highlighting potential differences in fractures across medication classes, our results highlight the need for continued research to better discern appropriate medication regimens for individual patients with the goal of improving overall risk reduction and producing better outcomes for individuals with ADHD.


ADHD is common in psychiatric populations. This study aimed to compare clinical characteristics in adults with and without ADHD who presented with self-harm, and to compare later risk of suicidal behaviour within 6 months.n = 93). Medical records were reviewed for evidence of subsequent suicide attempts (SA) within 6 months; suicides were identified by national register.Eight hundred four adults presented with self-harm  at psychiatric emergency services at three Swedish hospitals. Persons with a discharge ICD-10 diagnosis F90.0-F90.9 or a prescription for ADHD medication were considered to have ADHD (P = .005). A logistic regression model showed elevated risk of suicidal behaviour during follow-up in the ADHD group , although a final regression model suggested that this association was partly explained by age and comorbid emotionally unstable personality disorder.Recent relationship problems were more prevalent in the ADHD group. While the index episodes of those with ADHD were more often non-suicidal, and actual SAs more often rated as impulsive, medical lethality at presentation did not differ in attempters with and without ADHD. Subsequent SAs  were observed in 29% of the ADHD group and 20% in all others (Findings highlight the need for clinicians to take self-harm seriously in adults with ADHD.The online version contains supplementary material available at 10.1186/s12888-022-04057-0. Attention-deficit/hyperactivity disorders (ADHD) are common in psychiatric populations, and there are indicators that suicide risk may be heightened in persons with these disorders. In children and adolescents, studies have shown that ADHD predicts suicidal behaviour –5. This Problems of hyperactivity and attention deficit and related comorbidities may persist into adulthood , 11. Recn = 190), St Göran’s Hospital, Karolinska Institute, Stockholm (n = 479) and the Norrland University Hospital in Umeå (n = 135) in connection with a suicide attempt or an episode of non-suicidal self-injury (NSSI). As previously described [In total 804 patients  aged 18 and older were recruited and interviewed at three university hospitals .Participants were interviewed within a mean of 3.9 (Mdn = 3) days after emergency psychiatric consultation. Interview duration averaged 1–2 hours. All interviews were conducted by mental health staff  specially trained in the application of the assessment instruments . As prevAUDIT (Alcohol Use Disorders Identification Test)  was usedDiagnoses in connection with the index episode were retrieved from psychiatric records. Persons with discharge diagnoses F90.0-F90.9 according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10) were considered to have ADHD. Specific diagnoses in this group include ADHD, attention deficit disorder (ADD), dysfunction of attention, motor control and perception (DAMP) and other specified conditions of hyperactivity. In accordance with the Swedish study of Ljung and colleagues , having Actual suicide attempts in accordance with the C-SSRS  within 6T-tests were used to investigate group differences between patients with and without ADHD/subsequent attempts. Chi-square tests were used to compare proportions between the same groups. Mann-Whitney U Test was used for age group comparisons . Logistic regression models were used to calculate odds ratios for new episodes of self-harm with death intent and analyses were then adjusted for depression, emotionally unstable personality disorder (EUPD), trait impulsivity, sex and age (continuous variable). Similar regression models were created with data stratified by age group. Normality was assessed via visual inspection of histograms for deviations from normal distribution. All t-tests were cross-checked with non-parametric equivalents and yielded similar results. Statistical analyses were performed using SPSS® version 24 for Windows.χ2  = 1372, P = .01. For cases with partial missing data (n = 38), in total 5% of SUAS data, values were imputed. Where data was not imputed, cases with missing data were excluded from the current analysis. Details on other analyses where cases were excluded due to missing data are included in Tables Missing data was investigated using the SPSS Missing Value Analysis (MVA) module and for SUAS, BSA and MADRS tested for missingness mechanism, using Little’s Missing Completely at Random (MCAR) test. Missing data for assessment scales, identified as MCAR or missing at random (MAR) values were imputed by single imputation, using expectation maximum (EM) algorithm. For SUAS, data was treated as MAR instead of MCAR, Little’s MCAR test; A diagnosis of ADHD (ICD-10 F90.0-F90.9) was noted in the case record in connection with the index episode for 76 persons (10%). An additional 17 persons who did not have an F90.0-F90.9 diagnosis were prescribed pharmacological treatment for ADHD at the time of the index episode. Thus, for the purpose of this study, a total of 93 persons (12%) were considered to have ADHD. Methods employed at the index NSSI/SA are shown by ADHD status in Table For those with an actual attempt, self-poisoning was employed as a single method in 400 persons (60%); proportions were nearly identical in patients with and without ADHD.P = .08). Median age was lower  in persons with ADHD (Mdn = 29) than in those without (Mdn = 39). Participants with ADHD were less likely to have a clinical diagnosis of depression at discharge compared to those without ADHD, but proportions with anxiety disorder were similar. A clinical diagnosis of alcohol use disorder was somewhat less common in the ADHD group but the difference in proportions did not reach significance. Just over one tenth of the participants in both groups had a drug misuse disorder. Almost a third of those with ADHD had a clinical diagnosis of personality disorder, compared to one fifth of those without ADHD. Emotionally unstable personality disorder (EUPD) specifically was not more prevalent among persons with ADHD . Autism spectrum disorders were recorded in over one fifth of the participants in the ADHD group.NSSI at baseline was more common among those with ADHD Table . No gendTable P < .001). Among persons with a clinical diagnosis of depression, mean MADRS-S scores were higher in those with ADHD compared to those without . Anxiety scores were also higher in the ADHD group . Three quarters of those with ADHD reported having experienced recent relationship problems prior to index episode, a proportion higher than that observed in participants without ADHD.AUDIT data were available for 605 persons. Almost half of these (48%) had AUDIT scores above the WHO cut-off for hazardous use. Similar proportions of hazardous use were seen in participants with and without ADHD Table . For thoWhile proportions with psychiatric outpatient care after the index episode were similar between groups, patients with ADHD were more likely to have at least one subsequent consultation with psychiatric emergency services within the 6-month observation period Table . Particin = 138, χ2 = 4.67, df = 1, P = .03). Proportions with suicidal behaviour during follow-up in each group were only slightly attenuated after exclusion of participants with EUPD . Methods employed in connection with actual suicide attempts during the follow-up period are shown by ADHD status in Table P = .03). Two of the episodes among persons with ADHD were fatal, as were 8 of those in the group without ADHD .At least one suicide attempt or suicide death was recorded during the 6-month observation period in 29% of those with ADHD (27 out of 93). The corresponding proportion in the group without ADHD was 19% (2(1) = 4.59, P = .03) compared to those without. Risk of at least one fatal/non-fatal suicidal behaviour remained elevated for the ADHD group also after adjustment for clinical diagnosis of depression at baseline  = 3.97, P = .046). Adding EUPD to the model lowered impact of ADHD below the significance threshold, although not by much  = 3.22, P = .073). The predictive OR for EUPD was high in this model  = 24.30, P = <.001). Table 2(1) = 10.54, P = .001), but neither sex nor impulsivity were significant predictors.Stratified regression models on the low and middle age groups  did not yield significant ORs for ADHD. Stratified regression models are detailed in Supplementary Table SAll logistic regression models for the whole sample are detailed in Table 2 = 4.59, In this prospective study of adults who sought hospital care in connection with self-harm, we found that ADHD was associated with a particularly elevated risk of subsequent suicidal behaviour. Patients with hyperactivity disorders were less likely to have received a clinical diagnosis of depression and more likely to have a personality disorder. While the index suicide attempts of those with ADHD were more often characterized as impulsive, proportions with high medical lethality did not differ in suicide attempters with and without ADHD. In the total group, relationship problems were more prevalent in persons with ADHD.While a relatively small proportion (13%) of the patients with ADHD received a clinical diagnosis of depression in connection with the index self-harm episode, self-rated MADRS scores were higher in those with ADHD, both in the total group and in those with a clinical diagnosis of depression. This might represent an actual between-group difference in affective psychopathology, but another possibility might be that persons with ADHD perceive and self-rate the MADRS items differently than their peers without ADHD. It should be kept in mind that one quarter of the patients with ADHD also had a clinical diagnosis of autism spectrum disorder, which might impact on the manner in which they respond to the MADRS items . While tNeither alcohol use nor drug misuse disorders were more prevalent among persons with ADHD. Further, AUDIT scores and proportions scoring above the WHO cut-off for hazardous alcohol use were similar between groups. Taken together, these findings were somewhat unexpected as previous studies involving both clinical  and prisOne explanation for the increased risk for fatal/non-fatal suicidal behaviour during follow-up in those with ADHD might be the greater degree of impulsivity in patients with this disorder. For those 66 persons with ADHD whose index episodes were actual suicide attempts, these were characterized by impulsivity to a greater degree than in those without ADHD. It has been suggested that trait impulsivity might provide an important mechanism behind the shared genetic risk observed in ADHD and suicide . In our As far as we are aware, this is to date the largest prospective clinical study examining the relationship between ADHD and risk for future suicidal behaviour in adults who self-harm. Participants were well-characterized at the index episode, enabling comparisons of clinical characteristics between persons with and without ADHD. Using ADHD medication as a diagnostic proxy should improve diagnostic validity as these drugs are licensed in Sweden and may only be prescribed on strict indication by board-certified psychiatrists. Comorbidity was examined not only by clinical diagnosis but also by self-rating scales, yielding dimensional measures of affective symptomatology and problematic alcohol use. Trained mental health professionals carried out the interviews, which allowed us to expand on findings of previous register-based Swedish research by providing individual-level data on impulsivity, medical lethality, and recent relationship problems. The participation rate for this study was high, exceeding in total 70%. Both the wider age range  and the shorter follow-up time increase relevance of our findings for adult psychiatric services. The short follow-up interval is clinically relevant in an assessment of a clinical sample , especiaIn accordance with our ethical permission and the European General Data Protection Regulation law (GDPR), we were not allowed to collect any data on those who declined participation. Thus, comparisons between non-participants and participants were not possible and reasons for non-participation were not registered. We relied on clinical data to identify persons with ADHD, and a limitation is thus that we lacked a valid instrument for the evaluation of hyperactivity symptoms. Further, we had no objective measures of cognitive functioning and problem-solving style, which might differentiate patients with and without ADHD. Another consideration is that we did not have access to data on childhood and adolescent psychiatric history  which might contribute differentially to the suicidal process in participants with and without ADHD. We did not have access to information on specific types of psychological treatments administered after the index episode, and various forms of treatment could have had differential effects on new suicide attempts during follow-up. Prospective studies in diverse settings are called for to further characterize the clinical features and subsequent risk of self-harm behaviour in adults with ADHD.ADHD was prospectively associated with suicidal behaviour, although this association was no longer statistically significant when accounting for age and EUPD. Several of our findings might inform clinicians who evaluate and treat patients with ADHD and self-harm issues. As the proportion with high lethality attempts was just as large in those with ADHD as in those without ADHD, this highlights the need for careful evaluation in the clinical context. The finding that persons with ADHD were more likely to use hanging or strangulation during follow-up compared to those without ADHD suggests a tendency towards more violent behaviour. Taken together, our findings highlight that the higher degree of impulsivity in the attempts of persons with ADHD must not be mistakenly equated with low degree of suicide risk. Impulsive attempts are just as likely to result in medical injury as more planned attempts . AnotherAdditional file 1: Supplementary Table S1. Logistic regression models stratified by age groups, prediction of new suicide attempts  within 6 months.


Charonia tritonis. In this study, a short-type PGRP gene (termed Ct-PGRP-S1) was identified in C. tritonis. Ct-PGRP-S1 was predicted to contain several structural features known in PGRPs, including a typical PGRP domain (Amidase_2) and Src homology-3 (SH3) domain. The Ct-PGRP-S1 gene was constitutively expressed in all tissues examined except in proboscis, with the highest expression level observed in the liver. As a typical PRR, Ct-PGRP-S1 has an ability to degrade peptidoglycan (PGN) and was proven to have non-Zn2+-dependent amidase activity and antibacterial activity against Vibrioalginolyticus and Staphylococcus aureus. It is the first report to reveal the peptidoglycan recognition protein in C. tritonis, and these results suggest that peptidoglycan recognition protein Ct-PGRP-S1 is an important effector of C. tritonis that modulates bacterial infection resistance of V. alginolyticus and S. aureus, and this study may provide crucial basic data for the understanding of an innate immunity system of C. tritonis.Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition receptors (PRRs) involved in host antibacterial responses, and their functions have been characterized in most invertebrate and vertebrate animals. However, little information is available regarding the potential function of PGRPs in the giant triton snail  As we know, invertebrates rely solely on innate immunity to protect themselves against various microorganisms because they lack an acquired immune system as vertebrates have. Innate immunity employs several kinds of pattern recognition receptors (PRRs) to discriminate self from non-self, and initiate subsequent immune cascades to eliminate harmful invaders . PeptidoCrassostrea gigas [Since PGRP was purified and shown to bind specifically to bacterial PGN, activating an antibacterial response , subsequea gigas . To dateea gigas ,11. Accoea gigas ,13. The ea gigas , indicatIn recent years, studies focusing on marine PGRPs have made great progress. These marine PGRPs were proven to act as PRRs, opsonins, and bactericidal amidases similarly to their counterparts in terrestrial vertebrates . For exaC. tritonis is an endangered gastropod species of its ecological and economic importance [C. tritonis populations requires solid knowledge of biology and ecology, which can be further improved by studies on maintenance and breeding in captivity [C. tritonis are essential for understanding the evolution, diversity, and immune mechanisms of PGRPs as well as exploring effective strategies and efficacious immunomodulatory methods to control bacterial diseases in this important species. However, compared with the remarkable progress in insects and mammals or other marine animals, there is a research gap on the studies of C. tritonis PGRPs.portance . Protectaptivity . HoweverCharonia tritonis). Given that C. tritonis is an endangered gastropod species, we did not perform pathogens challenge assay to investigate which play the most vital roles in antibacterial immune response in C. tritonis. To further explore its characterization and potential functions, we obtained one full-length open reading frame of the cDNA sequence of peptidoglycan recognition protein Ct-PGRP-S1 and determined its mRNA expression patterns of Ct-PGRP-S1 in different tissues of C. tritonis. The recombinant Ct-PGRP-S1 protein was expressed, and its functions were characterized including amidase activity and antibacterial activity. It is the first report to reveal the peptidoglycan recognition protein in C. tritonis. These results suggest that peptidoglycan recognition protein Ct-PGRP-S1 is an important effector of C. tritonis that modulates bacterial infection resistance of V.alginolyticus and S. aureus, and this study may provide crucial basic data for the understanding of an innate immunity system of C. tritonis.Here, we identified a PGRP gene from the transcriptome of the giant triton snail (C. tritonis (NCBI sample ID: PRJNA695322) [Ct-PGRP-S1 (ID: Unigene31272_All), which was annotated as peptidoglycan recognition protein. The cDNA sequence of the open reading frame of Ct-PGRP-S1 was then determined by TA-cloning and deposited in Genbank under the accession number OP351736. As shown in Ct-PGRP-S1 is 867 bp in size, which encodes for a 288 a.a. protein precursor with a calculated molecular weight (MW) of 31.42 KDa.Based on the gene annotation of the transcriptome of A695322) , we obtaCt-PGRP-S1 contained an Amidase_2 domain and a SH3_3 domain  and Pomacea canaliculate (XP_025096405.1). Furthermore, a range of PGRP proteins from various gastropod mollusks was collected to study the evolutionary relationships by phylogenetic analysis. The results of the phylogenetic analysis revealed that our newly identified Ct-PGRP-S1 has the shortest evolutionary distance from the evolutionary distance from Littorina littorea and Batillaria attramentaria  [Blast analysis showed that the deduced amino acid sequences of mentaria A. Multipmentaria B showed ysteine) ,32,33, wCt-PGRP-S1 was analyzed in various tissues of C. tritonis by qPCR. As shown in Ct-PGRP-S1 was ubiquitously detected in almost all selected tissues except in proboscis, with the strongest expression level in the liver, followed by the mantle, tentacle and salivary glands.The mRNA expression pattern of Ct-PGRP-S1 was seen in the liver among three tissues , followed by the digestive glands and salivary glands. However, the RPKM (reads per kilobase per million mapped reads) of Ct-PGRP-S1 after feeding was upregulated significantly by more than 150-fold in the liver of C. tritonis but remained unchanged in digestive glands and salivary glands. It implied that feeding increases the expression of Ct-PGRP-S1 in the liver but has on impact on the transcript abundance of Ct-PGRP-S1 in digestive glands and salivary glands . rCt-PGRP-S1 was overexpressed after IPTG induction and subsequently purified by using Ni-NTA beads. SDS-PAGE analysis showed that the purified rCt-PGRP-S1 band was approximately 30 kDa , indicating that the amidase activity of rCt-PGRP-S1 was not Zn2+ dependent. This feature is inconsistent with previous results [2+ dependent. The result here suggests that rCt-PGRP-S1 has amidase activity toward PGN, but the amidase activity was not Zn2+ dependent.Based on the domain prediction A,B and h 120 min . However results ,21, whicV. alginolyticus  compared with the group without rCt-PGRP-S1, indicating that rCt-PGRP-S1 suppresses the growth of S. aureus bacteria.The inhibition effects of rCt-PGRP-S1 were investigated on the growth of olyticus A, V.chocholerae B, V. parolyticus C, E. col [PGRPs are a family of PRRs that play crucial roles in host innate immune responses ,34,35, a domain) ,35,36 anP. canaliculate (XP_025096405.1), D. polymorpha (KAH3862486.1), and M. mercenaria (XP_045194511.1). Src homology-3 (SH3) domains, consisting of approximately 60 amino acids, mediate intramolecular associations and form supramodules with their own supertertiary structures [As we know, most PGRPs contain one C-terminal PGRP domain (approximate 165 amino acids), which is homologous to bacteriophage and bacterial type 2 amidases ,12. Howeructures , which forpha KAH62486.1, ructures ,40. Bactructures ,42,43. Tructures . Therefo2+-binding residues, including two histidines, one tyrosine, and one cysteine [2+-dependent. This result was unexpected because the three Zn2+-binding residues in the PGRP domain were completely conserved in Ct-PGRP-S1. However, this is not an exception. Jaeeun et al. demonstrated that the absence or presence of metal ions, such as EDTA, Mg2+, Ca2+, Zn2+, or Mn2+, did not affect the lytic activity of endolysin, although it has three completely conserved Zn2+-binding residues in the PGRP domain [One common feature between invertebrate and vertebrate PGRPs is amidase activity, which hydrolyses the amide bond between MurNAc and L-alanine in bacterial PGN . Previoucysteine ,32,33. HP domain , which iC. tritonis are specialist predators of Acanthaster planci (crown-of-thorns starfish), which is important for the biodiversity of coral reefs and their biological communities [C. tritonis are considered vulnerable, and a decline in their populations will contribute to recurring population outbreaks of A. planci. Aquaculture has been considered as one effective approach that could help restore natural populations of C. tritonis and mitigate coral loss [Vibrio, since there are many reports of bacterial infection causing a massive economic loss in the aquaculture industry [S. aureus infections [V. alginolyticus and S. aureus by direct contact, reflecting the importance of Ct-PGRP-S1 in the antibacterial defense of C. tritonis and providing important evidence to suggest that amidase-active PGRPs may function as the key effectors to promote antibacterial response in hosts.munities . Howeverral loss . We coulindustry ,48,49,50fections ,53,54,55Ct-PGRP-S1, was identified in C. tritonis. Except in proboscis, the Ct-PGRP-S1 gene was constitutively expressed in all tissues examined, with the highest expression level was observed in liver. In addition, the recombinant Ct-PGRP-S1 has been proven to have PGN-degrading activity, non-Zn2+-dependent amidase activity and antibacterial activity against V. alginolyticus and S. aureus. To the best of our knowledge, the present study represents the first discovery on the function of PGRPs in C. tritonis, thus contributing to a better understanding of the functional evolution of PGRPs in gastropoda.In summary, a gene coding a short-type PGRP, named C. tritonis were obtained from Nansha archipelagic waters of the South China Sea. Tissue samples  were collected and quickly frozen in liquid nitrogen for 24 h, and then stored at 80 °C until total RNA extraction as previous described by Zhang et al. [The adult g et al. . The aniC. tritonis Ct-PGRP-S1 gene was found in a transcriptomic database constructed by our laboratory , and the open reading frame (ORF) sequence of Ct-PGRP-S1 was obtained using the primers annotated Ct-PGRP-S1-F/R . Prime-Script RT Kit with gDNA Eraser  was used for reverse transcription. TB Green® Premix Ex Taq™ II  was used for quantitative real-time PCR detection. Tissue expression pattern of Ct-PGRP-S1 was detected by quantitative real-time PCR (qPCR) using the gene-specific primers .Total RNA of multiple tissues, including salivary glands, tentacle, proboscis, mantle and liver from adult  primers , and 18sCt-PGRP-S1 gene except for the sequence of predicted signal peptide was amplified by PCR with the primer sets Ct-PGRP-S1-orf-F/R  to obtain a recombinant plasmid, which was transformed into E. coli BL21 (DE3)-competent cells. Subsequently, PCR and sequencing were used to check for the presence of the target genes with the primer pair pET28b-check-F/R.The cDNA segment (67–864 bp) including the full-length coding sequence of the -orf-F/R . The plaE. coli BL21 (DE3) culture was diluted into 500 mL fresh Luria broth (LB) with 50 mg/mL kanamycin (1:1000). The culture was incubated at 37 °C with shaking at 200 rpm until the cell density reached 0.6 at 600 nm optical density. Overexpression of recombinant proteins was induced by isopropyl-β-D-thiogalactoside (IPTG). Briefly, the culture was shifted to 28 °C and induced by IPTG at 0.5 mM final concentration. After 4 h of induction, the induced cells were harvested by centrifugation at 6000× g for 3 min at 4 °C. The cells were resuspended in 10 mL lysis buffer . Pressure cell disruptor  was used for cell disruption, and cell debris was pelleted by centrifugation at 15,000× g for 30 min at 4 °C. The supernatant was incubated with 2 mL of nickel agarose beads for 3 h with rotation. The slurry was eluted by using a 50–500 mM imidazole gradient. The reaction mixture was then passed through a nickel agarose column, and purified protein was concentrated using Amicon Ultra centrifuge tube  and stored in Tris buffer at −80 °C. The purified rCt-PGRP-S1 protein was characterized using 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Western Blot was carried out according to the methods described by Liu et al. [Bacterial Strain rCt-PGRP-S1-pET28b/BL21 (DE3) was grown overnight in LB medium plus 50 μg kanamycin at 30 °C with shaking at 200 rpm. Then, 500 μL of overnight u et al. . BrieflyS. aureus  was determined according to a previous method with minor modification [2 buffer  at 37 °C. Simultaneously, the Tris buffer without PGN was used as control group. The absorbance (OD) values were recorded at 540 nm per 10 min lasting for 120 min.The enzyme activity of rCt-PGRP-S1 toward PGN from Ct-PGRP-S1 protein was investigated according to the method described by He et al. [Escherichia coli and Vibrio alginolyticus, Vibrio cholerae, Vibrio parahaemolyticus and Gram-positive bacteria Staphylococcus aureus, grown overnight in LB medium at 37 °C. All cells were grown to mid-logarithmic phase (OD600nm ≈ 0.5). The bacterial growth rate method was used to investigate the antimicrobial activity of the purified recombinant Ct-PGRP-S1 protein. The purified recombinant protein was diluted with sterile Tris buffer  to final concentrations of 50 μg/mL, and 50 μL of rCt-PGRP-S1 was added to 900 μL OD600nm of 0.1 E. coli, V. alginolyticus, V. cholerae, V. parahaemolyticus, and S. aureus. Cultures (3 replicates in each case) were then incubated at 37 °C with continuous shaking at 200 rpm in 96-well plates. The wells in which the recombinant protein was replaced with Tris were used as the loading control. The wells in which the recombinant protein and the bacterial culture were left out were used as the blank control. OD600nm was measured at regular time intervals using the Multiskan Ascent plate reader . The antimicrobial activity of Ct-PGRP-S1 was measured by the growth kinetics or maximum cell densities of differenced bacteria.The antimicrobial activity of purified recombinant e et al.  with sli