The study of the relationship between adult Attention deficit hyperactivity disorder (ADHD) and bipolar disorder has received more attention in recent years and there is limited information in this area. On the other hand, there is a significant comorbidity between ADHD and bipolar disorder with substance use disorder. In this study, we investigated the prevalence of comorbidity of adult ADHD and substance use disorder among a group of bipolar patients admitted to a psychiatric hospital.One hundred fifty patients from a total of 200 consecutive patients who were referred to the emergency department of Roozbeh Psychiatric Hospital in Tehran, diagnosed with bipolar disorder based on the initial psychiatric interview and needed hospitalization, were evaluated again by an experienced faculty member psychiatrist by using a subsequent interview based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition(DSM-5).They were evaluated using the Structured Clinical Interview for DSM-5 (SCID-5) questionnaire to confirm the diagnosis of bipolar disorder and the comorbidity of adult ADHD and substance use disorder.p value = 0.025). There was no statistically significant relationship between substance use disorder and age of onset of the first episode. .From 150 patients diagnosed with bipolar disorder, 106 patients (70.7%) had adult ADHD. 89 patients (59.3%) had substance use disorder and 58 patients (38.7%) had both of these comorbidities with bipolar disorder. Comorbidity of adult ADHD was associated with the earlier onset of the first mood episode in bipolar disorder (Due to the limitations of studies on adult ADHD comorbidity with bipolar disorder, especially in hospital settings, as well as the increased risk of association with substance use disorder, further multicenter studies in this area with larger sample sizes can increase awareness in this regard. Although the global mental health survey estimates the prevalence of lifelong and 12-month bipolar disorder at 2.4 percent and 1.5 percent, respectively, there are many differences between countries that may be due to methodological or even cultural differences , 4.Early onset of bipolar disorder is reported to be associated with a lower prognosis, longer treatment delays, and more association with substance use disorders . Early aOn the other hand, with the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults and psychotic disorders in children and adolescents, the possibility of a link between ADHD and bipolar disorder has been raised more than ever . HoweverDespite various studies, the exact association between ADHD and bipolar disorder remains unclear in many respects . The resThere are various reports of a higher prevalence of ADHD among patients with bipolar disorder than in the general population  This issOn the other hand, the role of comorbidities associated with ADHD is important because of the long-term or lifelong nature of some of these disorders . Some stADHD, meanwhile, is a common comorbid disorder with substance use disorder with a worse prognosis . VariousThe earlier age of onset of bipolar disorder, due to its greater association with comorbidities and poorer prognosis, indicates the need for earlier diagnosis of the disorder and appropriate pharmacological and psychological therapeutic measures .Due to the limited studies conducted on the co-occurrence of adult ADHD and bipolar disorder and the need to achieve the diagnostic validity of these comorbidities on the one hand and the need to simultaneously pay attention to the comorbidity of substance use disorder with the above two disorders, in this study we have evaluated these important comorbidities among a group of patients with bipolar disorder admitted to a referral psychiatric hospital.The relationship between adult ADHD and bipolar disorder has been seriously considered by experts in recent years, and it seems necessary to fill the knowledge gap by conducting studies in different hospital / clinic settings and / or referral conditions. On the other hand, the comorbidity between bipolar disorder and substance use disorder, as one of the most common psychiatric comorbidities, has long been considered . The maiTrying to gain more insight into the pathophysiology of bipolar disorder associated with adult ADHD and substance use disorders, given the new therapeutic aspects involved and how to proceed with subsequent health care, can be the next steps in this evaluation .In order to achieve the appropriate sample size, using the sample size formula in the study of the prevalence of the disorders (the following formula), we obtained a relative estimate of the required sample size.In this formula, “n” is the number of participants in the study, “p” is the estimation of the ratio in the study population , “d” is the accuracy of estimating the prevalence and α is the estimation of the first type error.p = 0.5) who were referred to the emergency department of Roozbeh Hospital, the accuracy of estimating the prevalence of 0.1 (d = 0.1) and the first type error of 0.05 (α = 0/05), the sample size required to estimate the prevalence of bipolar disorder in this study was 96 patients. Finally, a total of 200 consecutive patients were considered as the sample size of the study.”According to the estimated prevalence of 0.5 of comorbidity of substance use disorder and ADHD among patients with bipolar disorder . They were evaluated using the Structured Clinical Interview for DSM-5 (SCID-5) questionnaire to confirm the diagnosis of bipolar disorder and the comorbidity of adult ADHD and substance use disorder.Also, for evaluation in terms of recent substance use, patients underwent urinalysis.Using the researcher-made questionnaire, other information such as demographic information, psychiatric history, etc. were obtained from the patient and her/his family. If any of the patients wanted to leave the study, they could leave it at any stage.This study was conducted between November 2019 and February 2020. Data collection in this study was done by one of the senior psychiatry residents of Roozbeh Hospital together with one of the psychiatry interns , under the direct supervision of a faculty member of the department of psychiatry of Tehran University of Medical Sciences. The various stages of data collection and analysis have also been performed under the direct supervision and execution of one of the statistical experts.All patients over the age of 18 referred to the psychiatric emergency department, who had admitted to hospital due to their psychiatric status after the initial assessment and had been diagnosed with bipolar disorder, entered to the study with informed consent.Exclusion criteria included the patient's unwillingness to continue attending the study at any stage of the study, as well as the patient's leaving the hospital for any reason, before completing the desired assessments.The emergency department and other hospital wards of Roozbeh Psychiatric Hospital in Tehran were the study sites. This hospital has 16 emergency beds and 220 beds in different wards. It is the largest academic psychiatric hospital in Iran and many of its patients are complex psychiatric cases who are referred from different hospital centers or other cities in Iran for diagnostic and therapeutic measures.In addition to inpatient wards, this hospital has a daily outpatient clinic for continuous outpatient care of patients discharged from the hospital as well as for other outpatient visits. The hospital also has a separate inpatient ward and outpatient clinic for the treatment of patients with substance use-related problems (in addition to patients with comorbid disorders with substance use disorder). The subspecialty ward of children and adolescents and the related outpatient clinic along with the occupational therapy and therapeutic exercise units and daily center for the care of patients with severe psychiatric disorders are other wards of this psychiatric hospital.In this center, patients with a variety of psychiatric disorders, especially patients with more severe symptoms and comorbidity with other psychiatric disorders and referrals with diagnostic and therapeutic complexities, receive medical and diagnostic care.The average number of annual visits in the emergency department of this hospital is more than 5000 visits. Trained psych-nurses are responsible for caring for patients without the need for the presence of companions. In a limited way and in necessary circumstances, court-mandated admissions are done in this center. The typical length of stay is between two weeks to one month, which is tried to be reduced to a minimum by expanding the support services such as social work services, providing various types of psychiatric and psychological care services and equipping the day center.This hospital is an educational and therapeutic academic center which is affiliated with Tehran University of Medical Sciences and the services provided in it are covered by various medical insurances. Patients and their families pay a limited fee for inpatient services or outpatient visits.Patients were included in the study based on the available sampling method and consecutive selection of patients based on the mentioned criteria and after obtaining written consent. Interviews and completion of relevant forms and the use of study tools were done after stabilization of the psychiatric conditions of patients in the emergency department or after transfer to the inpatient wards. In particular, the diagnostic evaluation for adult ADHD was performed at another time point after recovery from the acute episode.Also, especially in patients with acute manic / mixed episodes, special attention was paid to the symptom count level versus the diagnostic level in order to increase the accuracy in identifying the symptoms related to ADHD comorbidity. Regarding the patients in the mania episode, special attention was paid to the psychiatric history of the patients based on the history taken from the patients' families. Due to the severity of symptoms and short duration of initial symptoms in patients in this psychiatric referral center, in all cases, the interval between the onset of symptoms and the time of admission was less than one month before admission. Accordingly, in addition to examining patients in the last stages of hospitalization before discharge, the condition of patients in longer periods before hospitalization  was carefully considered and evaluated by an experienced psychiatrist and faculty member.In this situation, special attention was paid to the symptoms related to psychomotor activity, speech and concentration. The above symptoms were considered as part of the ADHD criteria if, in addition to the comorbidity of the symptoms in the recent episode, they were associated with a decline in social, educational or occupational function outside of the recent episode, according to the history taken. Also, focusing on the Diagnostic and Statistical Manual of mental disorders-fifth edition(DSM-5) diagnostic criteria, symptoms were considered ADHD symptoms only if they did not occur exclusively during the recent episode and were not better justified by other associated problems such as substance withdrawal or intoxication.SCID-5 is a valuable tool for use in clinical settings. Interview questions rate each criterion, whether or not they exist, according to SCID-5 diagnostic criteria . Osorio Mohammadkhani et al., have evaluated psychometric properties of Persian translation of this tool in terms of reliability and validity . They anIn this study, SCID-5 was used to diagnose ADHD. Somma et al., in their study, emphasized the reliability and validity of this tool for this purpose. In their report, they mentioned the general omega coefficient value 0.88. They also stated that general ADHD factor explained 81.0% of the SCID-5 ADHD criteria reliable score variance . Also inP values of < 0.05 were considered to be statistically significant.Statistical analysis was performed using SPSS v21. Continuous variables were summarized as mean (SD) and categorical variables as proportions (%). The relationship between qualitative characteristics was test using χ2 Test and Fisher's Exact Test. This study was performed based on the code of ethics obtained from the ethics committee of Tehran University of Medical Sciences with the code number IR.TUMS.MEDICINE.REC.1399. 421. All participants and their caregivers were aware of the study and how it was conducted when they entered the study. All the provisions of the Helsinki Declaration were taken into account in the implementation of this study. Study participants were assured that all information obtained from the study was confidential. Written informed consent was received from all the study participants and their caregivers.The total number of participants in the study included 150 patients with bipolar disorder referred to the emergency department of Roozbeh Hospital in Tehran who had been admitted to the emergency room. 69 (46%) of them were men and 81 (54%) were women. The mean age of study participants was 35.1 (standard deviation = 11.9) years. 65 of them (43.3%) were single, 57 (38.0%) were married, 24 (16%) were divorced and 4 (2.7%) were widows. Below diploma education with 67 patients (44.0%) had the highest prevalence in terms of level of education among participants. Other demographic information is provided in Table According to DSM-5 criteria, 64 (42.7%) were in the depressed episode and 86 (57.3%) were in the manic episode. 20(3.13%) patients were admitted for the first time and the rest had a previous history of psychiatric hospitalization.One hundred six patients (70.7%) had adult ADHD. 89 patients (59.3%) had substance use disorder. 58 (38.7%) patients had both adult ADHD and substance use disorder comorbidity. Fig.  72(48%) p value = 0.025 based on Fisher's exact test). In patients with bipolar disorder with the first episode under the age of eighteen, 68 patients out of 86 (79.1%), in the age group of 18 to 25 years, 30 out of 45 (66.7%) and in the age group over 25 years, 8 out of 19 (42.1%) and in total, 106 out of 147 patients (70.7%) had comorbidity with Adult ADHD.Comorbidity of ADHD was statistically associated with the earlier onset of the first episode in bipolar patients . In patients with bipolar disorder under study, in the age group under 18 years, 50 patients out of 86 (58.1%), in the age group of 18 to 25 years, 26 patients out of 45 (57.8%), in the age group over 25 years, 13 patients out of 19 (68/4%) and a total of 89 patients out of 150 (59.3%) had substance use disorder.There was no statistically significant relationship between substance use and the age of onset of the first episode . Out of 106 patients with bipolar disorder with comorbidity of Adult ADHD, 58 patients (54.7%) and out of 44 patients with bipolar disorder without comorbidity of Adult ADHD,31 patients (70.5%) had comorbidity of substance use disorder.There was no statistically significant relationship between comorbidity of ADHD in patients with bipolar disorder referred to the emergency department of Roozbeh Hospital and substance use disorder in them . However, there was no statistically significant relationship between substance use in bipolar patients and the age of onset of the disorder. Also, there was no statistically significant relationship between adult ADHD in bipolar patients and substance use.Attention to the comorbidity of these three disorders is especially important because in many studies, only limited comorbidities between some of these disorders are addressed. Also, the existence of these complex comorbidities is often associated with diagnostic complications and therapeutic resistance. This is especially reported in cases requiring hospitalization in referral centers.In a study of 56 patients with bipolar disorder, Sachs et al. examined the possible association between childhood ADHD and the early onset of bipolar disorder (the onset of the first episode under the age of 19) . They reIn a study in Italy, Masi et al. surveyed 59 patients with bipolar disorder under the age of 18 and reported that about a quarter of them had ADHD comorbidity at the onset of the first episode . They alAttention to inter-individual differences and variations in the context of the development of inattention symptoms is important in this regard. In general, different sets of genes have been reported as important and influential factors at the baseline and developmental coarse of ADHD symptoms .Also, paying attention to the impact of environmental factors on the course of the disease and the role of treatment and care measures in this field can be effective in forming the transfer of ADHD from one age period of life to another. In this regard, more emphasis is placed on the impact of environmental factors on neurodevelopmental processes. A point that can be changed to some extent with social context . In thisOn the other hand, Duffy, in a review study, stated that the clinical diagnosis of ADHD in children of patients with bipolar disorder is not a reliable predictor of bipolar disorder. However, he reported symptoms of anxiety and depression, as well as inattention among these children and adolescents, as part of the evolve of bipolar disorder based on some evidence. Also, in their study, the risk of ADHD was not increased among the children of patients with bipolar disorder . In our Wingo et al., in a systematic review, noted an increasing diagnosis of adult ADHD and highlighted the small number of studies related to comorbidity of adult ADHD and bipolar disorder . They deHowever, various studies report different prevalence of adult ADHD among patients with substance use disorders. According to some studies, the prevalence of adult ADHD in this group of patients is estimated at 13% . As the In an international study in 10 countries, Glind et al. reported an adult ADHD comorbidity with substance use disorder of 40.9% among 3,558 treatment seeking substance use disorder patients . In a stIn a study of 90 patients with bipolar disorder in the euthymic phase, Karaahmet et al. reported an adult ADHD comorbidity of 23.3% in these patients . This grNierenberg et al., in a study referring to the comorbidity of 60 to 90% of ADHD disorders in childhood and adolescence with bipolar disorder, described the prevalence and implication of this disorder in adulthood in bipolar patients as less clear  They repIn our study, which was performed on 150 hospitalized patients with bipolar disorder in an academic psychiatric hospital center in a continuous period of time, more than 70% of patients had commorbid of adult ADHD. According to the mentioned studies, patients with bipolar and ADHD comorbid disorders go through a more severe course of the disease. On the other hand, the psychiatric hospital where our study was conducted is the referral center for more complex psychiatric cases in Iran, therefore, this point may be one of the reasons for the high comorbidity rate between these two disorders in our study. Also, the use of accurate assessment tools for bipolar patients in terms of adult ADHD comorbidity and attention to the diagnosis of this disorder, can be effective in identifying this high percentage of comorbidity.Another important point in this regard is to evaluate the persistence of ADHD symptoms from adolescence to adulthood. In a study by Jahangard et al., the prevalence of ADHD in young adult Iranian students was reported to be 13.4–16.5% and estimated to be higher than worldwide prevalence rate . In theiAlso, despite some views on the increasing prevalence of substance use disorders in the early onset of bipolar disorder , in our Hunt et al. also described comorbidity between bipolar disorder and substance use disorder as common. They reported a comorbidity of 33% between the two disorders. They also reported the highest possible association with illicit drug use . As in oGarakani et al., in a review of 113 patients with a dual diagnosis of bipolar disorder and substance use disorder in an inpatient setting with a mean age of 32.6 years, reported a 24% prevalence of ADHD among this group . In theiAlthough comorbidity of substance use disorder in bipolar disorder is one of the highest rates of comorbidity in psychiatry, relatively limited conclusions and consensus have been reached on effective treatments for these conditions. This comorbidity can be associated with important effects on the recognition and management of bipolar disorder. Attention to integrated psychosocial interventions such as integrated group therapy (IGT) and other methods has been emphasized by some experts due to the difficulties of medication management in this group of patients along with psychopharmacological therapies and mood stabilizers such as Valproate , 79.Also, due to the high comorbidity of psychiatric disorders with ADHD, including bipolar disorder, the need to detect and treat these disorders is highly emphasized. Considering the use of stimulant medication to treat ADHD manifestations, after stabilizing the mood with mood stabilizers as well as restrictions on the use of stimulant medication when accompanied by motor tics and psychotic symptoms, are other recommendations .On the other hand, in many cases, not paying attention to the comorbidities mentioned in patients with bipolar disorder can be associated with negative therapeutic consequences and complex therapeutic resistance. This is an important point that can be considered by clinicians and requires full assessment of the severity of comorbid symptoms and related pharmacological and psychological treatments. This is especially important in terms of accompanying substance use disorder. In this regard, due to the limitations of related clinical trials in patients with bipolar disorder and comorbidity of substance use disorder (being in such a comorbidity status as a measure of exclusion criteria in many studies), we face a limitation in valid evidence for therapeutic interventions , 82. ThiAlso, the high prevalence of ADHD comorbidity among patients with bipolar disorder, especially in cases of high severity of symptoms, emphasizes the need for effective treatment of this disorder among these patients. Attention to effective treatment management in this field for the negative effects of some stimulants on mood and also, attention to some psychological interventions (despite the limited evidence of effectiveness) can be considered by clinicians .On the other hand, therapeutic resistance in cases with ADHD diagnosis, especially at younger ages, may indicate comorbidity with bipolar disorder. This can be accompanied by a marked increase in morbidity and disease burden among these patients. The possible comorbidity of substance use disorder at a later age can also lead to exacerbation of related symptoms and related diagnostic problems. This issue should also be considered by clinicians for the need for diagnostic attention and possible changes in psychopharmacological and psychosocial interventions and the creation of the necessary substrates by administrators and policymakers.One of the limitations of our study was its implementation in a hospital setting. In order to have more secure access to the information needed to complete the questionnaires and to ensure the patient history, it was necessary to ensure that the patients' psychiatric status was stable. It was also necessary to obtain information from patient caregivers in order to complete some parts of the history. Another important point was the complexity of the referral cases to the university hospital where the study was conducted. Thus, the focus of the study was on obtaining an accurate history of the patient's psychiatric illness.Also, due to some overlapping symptoms between mania episode and ADHD, such as increased psychomotor activity, speech and distractibility, the patients' condition was monitored regularly to assess the appropriate time for the interview. In addition, for this purpose, during the study, a close relationship was established with the patients' physicians. Other available resources, such as patients' families and caregivers, were also used to obtain more accurate information for diagnostic conclusions in obscure situations. Despite the best efforts made to accurately distinguish ADHD symptoms from the remaining symptoms of the mania / mixed episode, it seems that the use of other questionnaires related to symptom identification and diagnosis of ADHD, such as the Conners' Adult ADHD Rating Scales(CAARS), can help increase diagnostic accuracy. This point can be used in designing related future studies.Another point is that although there was no statistically significant relationship between ADHD in bipolar patients and substance use disorder, due to the limited sample size and the proximity of p value (0.07) to the cut-off point (0.05), the need for attention and continuation of studies with larger sample size and multi-center conditions are considered.In this study, one of the main goals was to investigate the comorbidity of substance use disorder with bipolar disorder. Accordingly, we have examined this disorder in relation to the use of alcohol and other non-alcoholic substances other than tobacco in order to more accurately investigate the use of illicit drugs in this group of patients.One of the strengths of our study was the assessment of the comorbidity of adult ADHD among complex cases with more severe courses of illness among many cases under study. This made it possible to achieve the prevalence of adult ADHD and substance use disorder comorbidity among this group of patients with bipolar disorder.In our study, a high prevalence of adult ADHD comorbidity was observed in patients with bipolar disorder during hospitalization. About two-thirds of patients with this comorbidity had a history of substance use. About half of the bipolar inpatients also had a history of substance use. However, there was no statistically significant relationship between substance use in bipolar patients and the age of onset of the disorder and there was no statistically significant relationship between adult ADHD in bipolar patients and substance use.There was also an association between adult ADHD and the early onset of bipolar disorder. Paying attention to mood symptoms among children and adolescents with ADHD can be helpful in early detection of cases with comorbidity of bipolar disorder in these patients and provide effective and needed treatments sooner.Also, due to the problems that exist in the identification and treatment of patients with adult ADHD worldwide, proper screening of patients with bipolar disorder is very important in terms of ADHD symptoms to achieve more effective treatment and more effective control of symptoms. In our study, there was no relationship between substance use disorder in bipolar patients and the age of onset of the disorder, which may indicate a less likely direct causal relationship between substance use disorder and the onset of bipolar disorder, especially in cases with early onset of the disorder. There was also no relationship between adult ADHD in bipolar patients and substance use disorder, which may have emphasized the important role of bipolar disorder in accompanying substance use disorder compared to ADHD. Due to the limitations of studies on adult ADHD comorbidity with bipolar disorder, especially in hospital settings, as well as the increased risk of association with substance use disorder, further multicenter studies in this area with larger sample sizes can increase awareness in this regard.Also, the results of our study emphasize the need for clinicians to pay attention to overlapping symptoms between bipolar disorder, ADHD and substance use disorder. On the other hand, diagnostic complexity in the case of comorbidity of the above two or three disorders emphasizes the need for early detection of the disorder in childhood and adolescence and at the school level. A point that can be seriously considered by health policy makers and administrators. Also, in this regard, the necessity of training teachers, experts and even clinicians to refer cases in a timely manner to specialized levels of psychiatry is emphasized.


Here, we aimed to understand the neural modulations of the attention networks underlying these improvements. Fifty boys (25 with ADHD) participated in a functional magnetic resonance imaging (fMRI) study in which unique (novel) or repeatedly presented (familiar) sounds were placed before a visual flanker task in 2/3 of the trials. We found that presenting any sound improved task performance in all participants, but the underlying neural mechanisms differed for the type of sound. Familiar sounds led to a stronger increase in activity in the left posterior insula in patients with ADHD compared to typically developing peers. Novel sounds led to activations of the fronto-temporoparietal ventral attention network, likewise in ADHD and TD. These changes in signaling by novelty in the right inferior frontal gyrus were directly related to improved response speed showing that neural orienting network activity following novel sounds facilitated subsequent attentional performance. This mechanism of behavioral enhancement by short distractions could potentially be useful for cognitive trainings or homework situations.Distractibility is one of the key features of attention deficit hyperactivity disorder (ADHD) and has been associated with alterations in the neural orienting and alerting networks. Task-irrelevant stimuli are thus expected to have detrimental effects on the performance of patients with ADHD. However, task-irrelevant presentation of  Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent disorders in childhood and adolescence  on behavioral attentional performance  as well as to utilize external cues to increase the readiness to respond (phasic). The behavioral advantage of using phasic alerting cues seems to be unimpaired in children with ADHD as they benefit from task announcing information similar to typically developing (TD) children  as well as the automatic allocation of attention toward changes in the environment (bottom-up)  as well as the influence of novel sounds to the baseline without sound and extracted the specific novelty effect (novel vs. standard sound).Here, we were interested in how alerting and/or orienting responses caused by novel sounds would influence brain activity and behavior during the subsequent execution of a visual flanker task  had to be excluded: In both TD participants and one patient with ADHD we incidentally found brain abnormalities . Two more patients with ADHD performed at chance level, which we interpreted as either lack of motivation or severe misunderstanding of the task. Thus, the final sample consisted of 25 ADHD patients and 25 typically developing children and adolescents . All parTwelve patients were currently on stimulant medication (11 methylphenidate / 1 dexamfetamine) and discontinued the intake at least 24 h before and during the experiment. Four ADHD patients previously took stimulants (discontinued on average for 2 years) and nine were medication naïve.Twenty participants were diagnosed with the combined subtype of ADHD, three with the predominantly inattentive subtype and two with the predominantly hyperactive-impulsive subtype. Furthermore, six participants in this group met diagnostic criteria for a comorbid oppositional defiant disorder (ODD). The comparison group of TD children paralleled the ADHD group in terms of age but displayed significantly higher IQ values and scores of attentional abilities .The behavioral task consisted of a modified version of the Eriksen flanker task . We further assessed the individual measures of spectral content , spectral structure (harmonics-to-noise ratio) and temporal variability (standard deviation of frequency and amplitude) of each sound stimulus via Praat software (www.praat.org)  cut to be of equal duration of 500 ms and edited to match in volume (60 dB) using the software Audacity .The experimental session started with a training block of the task  outside the scanner. During training, novel sounds were not included, but half of the trials were preceded by the individual standard sound. Participants had the opportunity to repeat the training, if necessary and to ask questions. In the scanner, a comfortable volume level was adjusted under scanner noise individually for each participant. Then, participants performed three experimental task blocks with 120 trials each . Visual and auditory stimulation as well as recording of responses took place 3 .FMRI scanning took place on a 3T Philips Achieva dStream using a 32-channel head coil. A high resolution individual T1-weighted structural image was first collected in 192 sagittal slices with a voxel size of 1 mm3. Then, 290 whole-brain functional images were measured for each experimental run. An echo planar imaging (EPI) sequence parallel to the anterior-posterior commissure in axial planes was utilized. The sequence acquired 35 slices in ascending order with a spatial resolution of 3 mmPreprocessing and statistical analyses of the functional images was realized with the Statistical Parametric Mapping software  running on Matlab Version 2021b . Preprocessing with SPM encompassed realignment to the first image in the respective run and co-registration of all images to the individual mean. Functional images were then spatially normalized to the anatomical T1 template provided by SPM  and smoothed with a 6 mm FWHM istotropic Gaussian kernel. A highpass filter was applied at a cutoff of 1/128 Hz to remove low-frequency drifts.lmer function of the lme4 package and included a random intercept for participants as well as age as covariate of no interest. The fixed main effects and interaction of the factors Sound (novel vs. standard vs. no) and Group (ADHD vs. TD) were modeled and tested using Wald tests (Type-II ANOVA tables) in the car package. If applicable, post-hoc t-tests were calculated. In a second step we directly tested for differences between standard and novel sounds minus baseline with the same model approach [fixed effects for sound  and group].The behavioral measures of interest were changes in accuracy , mean reaction time (RT) and the coefficient of reaction time variability  for novel and standard sounds vs. the baseline without sound. First, we used linear mixed effects models to investigate the overall effects of the sound manipulation and ADHD on accuracy, RT and RTV. All models were computed in R statistics with the Furthermore, partial correlations controlling for age (ppcor package) were calculated to investigate the relationships between changes in task performance  and changes in neural signaling between novel and standard sounds in areas of interest as well as between these measures and IQ, d2-task performance and ADHD symptoms , respectively.Statistical analysis with SPM was based on the general linear model (GLM) approach. Individual GLMs included the three effects of interest (three sound conditions) and two effects of no interest  as well as 24 additional nuisance regressors based on the co-registration step during preprocessing to account for volume-to-volume head motion . Moreover, the absolute difference between odd and even slices and slice variance were used to estimate within-volume motion for each TR. These regressors were included as further confounds in the GLM and were used to identify excessive motion (>4 × SD) in single volumes. These volumes were excluded using additional volume-specific regressors. Finally, the canonical hemodynamic response function time-locked to the onsets of the flanker task display was used to convolve the regressors. Then, individual contrast images were generated for the contrasts of interest to be used for second level group statistic.t-tests). Then, we used two-sample t-tests to compare participants with and without ADHD regarding activity during standard > no sound baseline, novel > no sound baseline as well as novel > standard sound trials. An additional age regressor was included in all group contrasts to account for the wide developmental range. All contrasts were initially calculated with a threshold of p < 0.001 (uncorrected). The results were then corrected for multiple comparisons using a cluster-level false discovery rate (FDR) of p < 0.05.Second level analysis of the fMRI data aimed on the one hand to investigate the neural basis of beneficial sound effects particularly in children and adolescents with ADHD. On the other hand, we wanted to disentangle the effects of alerting by standard sounds and alerting/orienting by novel sounds during task performance in general. Therefore, we first inspected group-wise activations associated with standard sounds as well as novel sounds compared to the baseline without sounds in each group. In the same manner, we determined the specific effect of novelty by contrasting novel with standard sounds per group , we computed the contrasts of interest over all participants, extracted percentages of signal change from the peak voxel and calculated partial Pearson's correlations between these measures controlling for age.p = 0.0009] and that sounds had a significant influence on accurate responding [main sound: p = 5.02e-13]. The repeatedly presented standard  as well as the novel sound  improved accuracy compared to the baseline without sound. Moreover, the effect of both sound conditions was elevated in the ADHD compared to the TD group [interaction: p = 0.005].An overview over the changes in task performance from baseline by novel and standard sounds in children and adolescents with and without ADHD is depicted in p < 2.2e-16] and participants with ADHD responded overall more slowly than TD children and adolescents [main group: p = 0.00038]. The coefficient of response time variance (RT) was not influenced by group or sound as defined in the model . When pooled together, we however did see a significant decrease in RTV for sounds vs. no sound baseline .Average response times were accelerated by both sound conditions compared to no sound [main sound: p = 0.012]. But they also revealed no differences between novel and standard sounds [p = 0.228] nor did we see differential effects per group [p = 0.228].To further explore the individual changes of novel and standard sounds and control for differences in the baseline, we used the respective differences to the no sound baseline for a direct comparison between novel and standard sounds. These models confirmed the overall greater increase in accuracy of both sounds on participants with ADHD (on average 6% improvement) compared to their typically developing peers (on average 2.48% improvement) [p > 0.18) but we found a trend of an interaction between sounds and group on RTV [p = 0.09]. This trend resulted from a tendency of RTV to be reduced more by novel compared to standard sounds in the patients with ADHD whereas TD peers displayed the opposite trend of an increased benefit from standard sounds . None of these results changed significantly when only ADHD patients with combined presentation were included (N = 20).via t-tests in each group (one-sample) and then compared between groups (independent sample)  . For bot sample) . A simil sample) . The finIn line with these group wise contrasts, group comparisons revealed no difference between the groups in brain activation following novel sounds (neither when compared to the baseline without sound nor to standard sounds). However, the comparison of activity pattern evoked by standard sounds during task execution (standard > no) revealed enhanced activation for ADHD patients compared the TD peers in the left posterior insula extending to the putamen (depicted in the group clusters in N = 50) to identify a common network of novelty-related brain activation during task execution  and right STG  as well as rIFG  for the whole sample .As we could not detect novelty related differences in neural activity between children and adolescents with and without ADHD, we collapsed over all participants . Exploratory inspection of this relationship between rIFG activity, group and RT revealed that the correlation was based upon the participants with ADHD. When considered alone, the patient group showed a correlation of r = −0.45 (p = 0.02). TD peers, on the other hand, displayed a weaker relationship that failed statistical significance   and used these parameters to identify correlations between brain activity and task measures of interest . We found a significant negative correlation between neural activity in the rIFG and the difference in mean RT across all participants ( = 0.15) . No assoThe current study aimed to identify activity in neural attention networks that underlie the beneficial effects of task preceding sounds on subsequent performance in children and adolescents with and without ADHD. We were particularly interested in the effects of unique (novel) sounds compared to a repeatedly presented standard as both types of sounds should function as alerting cues, but only novel sounds were supposed to elicit an orienting response.We found that novel sounds caused activity in large bilateral clusters spanning the STGs extending to anterior TPJs as well as the right IFG in all participants, without detectable alterations in patients with ADHD. This network is in line with former descriptions of the ventral attention (orienting) network (VAN)  or specific characteristics of the ADHD sample. We only included males and about half of our ADHD sample had used stimulant medication over the lifespan. Twelve patients currently took medication and although they discontinued the intake for at least 24 h, it cannot be ruled out that responsivity to the task preceding tones is altered in comparison to medication naïve participants.Overall, we showed that sounds acting as warning cues can improve performance in all participants but particularly in ADHD patients. Moreover, and potentially caused by an underlying disorder-specific alertness deficit MRI data from the underage study participants was not obtained for ethical reasons. Behavioral data, group fMRI data and code will be made available upon reasonable request from the corresponding author. Requests to access the datasets should be directed to The study was reviewed and approved by the Local Ethics Committee of the Otto von Guericke University, Faculty of Medicine. Participants and their legal guardian received a detailed oral and written information about the study procedure. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. Participants were also asked to provide written assent.JT, AB, BB, H-HF, and KK designed the study. JT and CB-Z performed the experiment. JT and KK analyzed the data and wrote the manuscript. AB, CB-Z, BB, and H-HF edited the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the Deutsche Forschungsgemeinschaft .The 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Though many adults with ADHD underperform professionally, are more stressed, and have more days of sickness absence compared to adults without ADHD, few studies have explored the experience of working as an adult with ADHD. This study explores the general experience of working with ADHD, including stress and work-related mental illness.Semi-structured telephone interviews were conducted with 20 working adults with ADHD. Interview topics included how the ADHD diagnosis and/or symptoms of ADHD may have affected participants on the job, how work may have affected participants’ well-being, and the need for support and accommodation. Qualitative content analysis was used to explore verbatim transcripts from the interviews.Working and living with ADHD, Needs, and Special abilities, with a total of eight subcategories. Subcategories were Specific challenges; Relationships and cooperation; Negative consequences; Planning, prioritization, organization, and structure; Support, interventions, accommodations, and aids; Openness, understanding, and acceptance; Strategies; Strengths and qualities.The analysis yielded three themes that describe some of the challenges of working with ADHD: Further knowledge about the challenges of working with ADHD is needed in workplaces; where organizational support is lacking, much in terms of accommodations and aids is up to the employee, and the disclosure of diagnoses may be associated with great dilemma.The online version contains supplementary material available at 10.1186/s12888-022-04409-w. During the last two decades, the proportion of sick leave in Sweden due to psychiatric diagnoses has increased drastically. In 2016, psychiatric diagnoses accounted for 27% of newly registered and 44% of ongoing sickness cases . The incAdults with attention deficit hyperactivity disorder (ADHD) may have particular difficulties balancing work, leisure, and family, and run a high risk of suffering from mental illness. ADHD is characterized by symptoms of inattention, hyperactivity, and impulsivity. It is one of the most common psychiatric disorders among children and adolescents, and for most patients, symptoms persist throughout adulthood, with associated negative outcomes on both individual and societal levels . WorldwiMany adults with ADHD underperform academically and professionally, compared to their intellectual potential . ADHD adThe relationship between workaholism and ADHD has been demonstrated by Andreassen et al. , among oThe relationship between symptoms of ADHD and stress has been demonstrated by Combs et al. , among oResearchers studying the economic burden of adult ADHD point to increased costs for sick leave . De GraaIn a study of ADHD outpatients aged 19 to 29 years, 38% received sickness absence recommendation, compared to 2.4% in the general population receiving that benefit . All patIn Sweden, the position of professionals with ADHD in the labor market has been emphasized by government agencies , patienIn one of the most comprehensive qualitative studies to date, Brod, Pohlman, et al.  conducteInterviewing adults with ADHD between the ages of 21 and 38, Ek and Isaksson  found thdivergent thinking, hyper-focus, and nonconformist.Studying experiences of young adults with ADHD and the role of context, Lasky et al.  report tInterviewing a well-educated, high-income sample of older adults with ADHD, Brod, Schmitt, et al.  report tQuantitative studies of occupational issues among adults with ADHD tell us much about the negative consequences of working with ADHD. While previous qualitative studies provide further insight into the experiences of working with ADHD, more research is needed on how adults with ADHD experience their working life. This includes specific occupational challenges, successful strategies for coping, and the relationship between work and mental health. This project aims to further study the general experience of working with ADHD, specifically explore stress and work-related mental illness among adults with ADHD, and identify needs in preventing these negative outcomes.In-depth interviews with 20 adults with ADHD were conducted between May and July 2021.Participants were recruited primarily in collaboration with a large Swedish ADHD patient interest group, Riksförbundet Attention. Information about the study was published on social media, together with a link to a website where interested individuals were invited to read more about the study. Terms and conditions were detailed on the website. Before recruitment, the study received ethics approval from the Swedish Ethical Review Authority (Diary number: 2021–01029). Participants were required to be 20–64 years old (Swedish definition of working age), have a diagnosis of ADHD, speak Swedish, work half-time or more, and have work experience equivalent to at least three years full-time. No compensation was awarded for participation. Provision of informed consent was required to submit a notice of interest, thus, written informed consent was obtained from all participants. With this notice, data were collected regarding age, gender, education level, occupational status, work experience, and ADHD diagnosis. Finally, participants submitted their email addresses. In a few days, 90 notices of interest were submitted, and the website was closed to new submissions. All participants were given a random identification code , and their contact information was stored separately from all other data. Thus, participation was pseudonymous.From the pool of notices of interests, 20 individuals were chosen purposefully and stratified to reach a heterogeneous sample concerning demographics. Half identified as women, half as men. Ages ranged from 23 to 60 years, education level ranged from high-school degrees to more than three years of university studies, and work experience ranged from 5 to 40 years. These individuals were contacted via email and invited to schedule an interview. If unavailable, or not responding, another individual of similar age and, if possible, the same gender was contacted. In total, 61 individuals were contacted before 20 interviews had been scheduled and conducted. Table Semi-structured interviews were conducted via telephone by authors M.O. and M.N. The interviews were recorded using digital audio recorders. All recordings were transcribed verbatim by the interviewers. Identifying information was substituted with generic analogs, e.g., “employer”, “city”, or “care provider”.An interview guide was used through all interviews All participants described specific challenges related to working with ADHD, concerning symptoms and/or situations. Among the prominent symptoms were those commonly associated with ADHD, such as distractibility, forgetfulness, restlessness, impulsivity, and impatience. Also prominent were symptoms less typically associated with ADHD, such as emotional dysregulation. Many participants described a hypersensitivity to criticism and failure, and a general sensitivity to changes in mood and atmosphere in and around the workplace, negatively affecting work performance and psychological well-being:I get really stressed out from knowing we won’t get through the agenda. It makes it hard to focus on anything else than seeing the time run out and knowing we won’t finish. It also makes it impossible for me to keep up with the discussion. I can’t keep up with the discussion while focusing on what I think the meeting should really be about. It’s too many discussions and conversations at the same time, on different topics in different areas. (Participant B)The sample was heterogeneous regarding professions, and, as such, challenging situations varied between participants. Recurring, however, were monotone and repetitive tasks, which caused under-stimulation, boredom, and subsequent dejection. Another typical challenge were meetings. Problems with meetings included difficulties staying focused and keeping up with the discussion, trouble gathering one’s thoughts while conversations derail, and stress building up as meetings go overtime:It’s taken a while for my colleagues. They’ve thought I’ve been angry or, well, been in the mood. They feel it’s a little uncomfortable. And I’ve told them what’s what, that I’m saying whatever I’m feeling or thinking, out loud. (Participant C)A large majority of participants mentioned experiences of working alongside and together with other people, and how those encounters affected their experiences of working with ADHD. Prominent was the sense of other’s, imagined or true, judgment of oneself. Some participants described coming across as lazy, ignorant, or incompetent, when dysexecutive. Others described repeatedly being perceived as too much or too straightforward. Many also recalled a history of faux pas in the workplace, as a result of tactlessness and indiscretion:A feeling of impending danger, unease, but you never know what for. It afflicts everything you’re thinking about in that moment. (Participant D)It’s not like you have anxiety for a moment and then you’re good. It just lays there, like a tone, disturbing. (Participant E)Whether participants enjoyed their job, had a good relationship with colleagues, and felt support from management in their vocational aspirations, they all described indisputable negative consequences of ADHD, related to their work. These consequences included negative effects on family and recreation, loss of jobs, unemployment, and symptoms of mental illness. Most prominent among symptoms of mental illness were anxiety, stress, and exhaustion. Several participants described a working life marked by constant anxiety, with spikes in intensity related to work and life events:Regarding stress, many participants described a general sensitivity to stress and feelings of being easily overwhelmed. This was related to feelings of not doing good enough, not keeping up with tasks, and not staying on top of things. For many, this was mediated by symptoms of inattention, such as distractibility and forgetfulness. Some compensated by being exceedingly thorough or working overtime, further depleting their energy reserve. Several participants described being “weathered” by years of stressful work and repeated relapses of exhaustion.If I’m stressed out, and ashamed, and feel stupid, I perform worse at work, too. The effect is crystal clear. In the moments I’m a little happier or more positive, I also perform better. (Participant B)Just as work affected their mental health, many participants also described how their mental health affected their work, positively and negatively:Many participants described circumstances outside work that aggravated the challenges of working with ADHD. Most pronounced were trials related to family and parenthood. Several participants mentioned having children with special needs of their own, and the challenges of working while accommodating them. Not knowing if your child will be able to get out of bed in the morning when you have an important meeting, managing appointments with pediatricians, and always being on-call if something happens at school, introduces another level of strain. A number of participants described the work-family balance as “unmanageable”, fighting to uphold a low-arousal approach when returning home from work, battered.In contrast to specific challenges, negative consequences, and aggravating circumstances, all participants shared thoughts about their current needs, as well as their experiences of successful and unsuccessful interventions, accommodations, and collegial/managerial support.All the little things like deciding for yourself in what order things should be done, how they should be done, what exactly we are in need of… Those things take a lot of time and energy for me, which it doesn’t always do for my colleagues. (Participant F)Many participants experienced great deficiencies in organization and structure at their workplaces, encumbering not only themselves and fellow coworkers with ADHD, but most, if not all, employees. Some described lacking job descriptions and not knowing what to do, leading to a loss of time and energy:The structure of having a job helps me out a lot in my spare time. I never take more than ten days off from work, because I don’t want to. I need the trot of working, to maintain any kind of structure in my life. (Participant D)Participants with experiences of working with clear-cut job descriptions, explicit routines, and consistent implementation, on the other hand, recall thriving and outperforming colleagues. For some, the benefits of structure at work carried over to personal life:The answer is always “what can you do to make it better?”. I feel like I’m doing everything I can. (Participant B)Experiences of managerial support varied greatly between interviews. While many participants described supervisors and managers as being supportive, the responsibility for designing and implementing accommodations was often appointed the individual:While the experiences of managerial support varied, many participants described supervisors and managers as important or crucial in their experience of working. Certain weight was given to the general attitude of superiors regarding support, and several participants described how a perceived lack of responsiveness could be considerably discouraging. Some participants had greater success working with colleagues to adjust routines and processes in the workplace. For example, some participants had agreements with team members regarding the distribution of tasks. Others found great support in colleagues with similar or other special needs of their own.I have a very detailed to-do list on my computer. I move things around on the list, rather than checking them off, so that I can see I’ve made progress. … The way I’ve set that up, I’ve come up with myself. (Participant E)Although a small number of participants used assistive technology, such as visual timers and screen readers, very few had been in contact with an occupational therapist. Most participants, however, used mobile and computer applications to organize, plan, and prioritize their work, including intelligent to-do lists, reminders, calendars, and timers. In all cases, the selection and implementation of such applications were done by participants themselves, without professional assistance:Regarding healthcare support, many participants described significant improvements in functioning at work following pharmacological treatment of ADHD symptoms. Experiences of other interventions in routine psychiatric care, however, were scarce, and generally disappointing. For example, some participants recalled experiencing a lack of knowledge among healthcare providers, beyond basic diagnostic criteria for ADHD. Several participants desired interventions catered to relatively functional adults, focused more on executive function rather than basic organization skills.I’ve gotten used to being open with my needs, both with my colleagues and with my boss. I usually don’t talk about my diagnosis, but I wouldn’t lie if someone asked. However, I do feel that I have to be open with the fact that I need help organizing things. (Participant G)Many participants described how coming to terms with their ADHD-related deficits, often through diagnosis and subsequent (self-)education, enabled them to work constructively with their challenges at work. For some, it also facilitated self-compassion. Experiences of disclosing the diagnosis at work, however, varied. Some shared it confidentially with select colleagues, some only with their closest supervisor, and some spoke openly about it. Other participants were vocal about specific deficits, symptoms, and challenges, rather than disclosing their diagnosis:Responses to disclosure also varied. Some participants experienced significant relief and improved relationships with coworkers. Others recall supervisors and managers not knowing how to deal with the information, and a general lack of understanding of the challenges of adult ADHD. Many participants described a dilemma surrounding disclosure. On the one hand, disclosure may facilitate accommodation, while raising awareness. On the other hand, a diagnosis should not be a prerequisite for accommodation, and the actual informational value of a diagnosis is limited. Several participants also feared discrimination or bias.While there was a clear consensus among participants that advantages of ADHD symptoms or an ADHD diagnosis were slim to none, nearly all participants described acquired strategies, personal strengths, and unique qualities that significantly improved function and sometimes alleviated burden at work.During a day, I often make lists of things I feel discontent with. That way, I have them recorded to return to, instead of carrying them with me and feeling it’s something personal. You have to maintain a more pragmatic view of things. (Participant H)Many participants employed formal analysis and rigorous problem solving to understand and deal with challenging situations and circumstances at work. Some described performing it on the spot when faced with a challenge, while others made notes of situations during the day to later analyze and try to remedy:Together, the participants described a wealth of solutions to challenges at work. Beyond positive effects of the beforementioned analyses, efficient approaches included stimulus control, frequent breaks, and intentional gaps in the agenda. Many participants also mentioned successful preventive strategies, including engagement in exercise, outdoor life, and other valuable pastimes.I find it easy to come up with multiple ways to solve a problem, and I’m able to choose between them. Also, I never get stumped in a situation, whereas I often see colleagues get completely paralyzed. (Participant E)Many participants described a certain creativity and quick-wittedness. This would be expressed in situations such as brainstorming meetings and problem solving, as well as in social settings. For some participants, these traits would go hand in hand with a perceived above-average ability to think outside the box and come up with effective solutions when colleagues and partners were stuck:I have a huge number of ideas of things to do. I’ve learned to keep quiet about that, sometimes, because you always end up having to do them yourself. (Participant E)However, many participants described their wealth of ideas as both a blessing and a curse, as concurrent impulsivity could lead one to express ideas, including possibly controversial ones, in situations where one would be better off keeping quiet:Some participants described a positive ability to hyperfocus, being able to direct all their attention to the task, activity, or client at hand, or being able to quickly assimilate crucial information on a topic. A few participants also described certain positive effects of hypersensitivity, such as being able to instantly pick up on changes in mood, attitude, or atmosphere in important meetings, and being able to better empathize with clients.This study explored self-reported ADHD-specific experiences of working with ADHD, including work-related stress and mental illness. Qualitative content analysis of transcripts from 20 interviews revealed three themes of common experiences. The results expand our knowledge on how ADHD adults experience their working life, including specific occupational challenges, experiences of previous interventions, current needs, special abilities, and strategies for coping.Regarding living and working with ADHD, all participants described specific challenges concerning certain symptoms and situations. In addition to the familiar ADHD symptoms of inattention, hyperactivity, and impulsivity, many participants described a prominent burden of emotional dysregulation, as well as general social hypersensitivity. While current diagnostic criteria for ADHD does not include emotional dysregulation as a core symptom, it has been extensively discussed in the literature whether problems with emotional regulation should be considered a primary symptom of (adult) ADHD e.g., –39). Bar. Bar39])Concerning the consequences of living and working with ADHD, several participants described careers characterized by persistent anxiety, stress, and relapses of exhaustion. As previously shown, the association between ADHD, stress, and mental illness, is well documented in quantitative studies. The results of the current study expand our understanding of this relationship, identifying feelings of being overwhelmed, not doing good enough, not keeping up with tasks, and not staying on top of things, as related to perceived stress and overload.Regarding interventions, accommodations, and collegial support, many participants described negative effects of inadequate organization and structure at their workplaces, while some described thriving under better managerial circumstances. The importance of clarity in communication between managers and employees with ADHD has been emphasized by ADHD experts  and manWhile many participants described a significant improvement in working ability after pharmacological treatment of ADHD symptoms, experiences of any further support in healthcare were few and unsatisfactory. While the effectiveness of medications for adult ADHD is well documented , nationFor many participants, circumstances outside work, including family and parental obligations, aggravated the challenges of working with ADHD. However, nearly all participants also described strategies, strengths, and qualities that improved function and alleviated burden. For many participants, formal analyses and problem solving, combined with creativity and quick-wittedness, was a recipe for progress at work. While planful problem solving is a challenge for some with ADHD, these results are in line with the adult-ADHD tendency to positively reappraise current situations and “continually assess, re-assess, compensate and adapt” ( p.814). Qualitative content analysis was used to explore the content of the interviews. The interviews were conducted and transcribed by the authors who later performed the analysis, making for great familiarity with data and the manifest content . For trupre-understanding, i.e., their knowledge of the subject and their familiarity with the context [In all qualitative research, researchers must take into consideration their  context . In this context . In the The limitations of the current study include the recruitment and sampling process. In the information about the study, the aim of studying work-related stress and mental illness was explicit. It is possible that this framing attracted certain interest from adults with ADHD and a more extensive history of stress and work-related mental illness. While this was of interest in the study, perhaps the sample would have been more heterogeneous had the initial information been less specific. The sample did, however, have an appropriate range regarding age, work experience, education level, and profession.Future studies may well consider ethnographic methods to further study the challenges of working with ADHD. For example, researchers may consider observing adults with ADHD in the working environment, to gain further knowledge of specific settings and situations that prove challenging. Future research could also focus on the managerial partners in organizations, e.g., experiences of supervising employees with ADHD and managing the challenges and consequences of ADHD in the workplace.The results of the current study suggest further knowledge about the challenges of working with ADHD is needed in workplaces; where organizational support is lacking, much in terms of accommodations and aids is up to the employee, and the disclosure of diagnoses may be associated with great dilemma. The results of the current study may also inform other social partners, e.g., labor organizations and work environment authorities, and advise regulations, recommendations, and legislation. More knowledge is also needed in health care, where, other than medications, common interventions in routine psychiatric care seem to generally disappoint working adults with ADHD. While psychoeducational interventions on ADHD in general may be provided, participants in the current study asked for interventions catered to relatively high-functioning patients, and the specific challenges they may be facing.Additional file 1. Interview guide.


Is an attention-deficit/hyperactivity disorder (ADHD) diagnosis in childhood or early adolescence associated with quality of life in adolescents compared with age-, sex-, and behavior-matched individuals without a diagnosis?In this cohort study, 393 adolescents with an ADHD diagnosis reported similar quality of life overall and on 3 subdomains but significantly worse outcomes for 5 other aspects of quality of life compared with 393 matched adolescents with similar levels of hyperactive/inattentive behaviors but no ADHD diagnosis.These findings suggest that childhood ADHD diagnosis may not result in any improvements in quality of life measures in adolescents and may negatively impact some outcomes, such as risk of self-harm. This cohort study examines quality of life in adolescents who have received a diagnosis of attention-deficit/hyperactivity disorder compared with peers with matched hyperactive/inattentive behaviors but who have not received a diagnosis. Appropriate diagnosis of attention-deficit/hyperactivity disorder (ADHD) can improve some short-term outcomes in children and adolescents, but little is known about the association of a diagnosis with their quality of life (QOL).To compare QOL in adolescents with and without an ADHD diagnosis.This cohort study followed an emulated target trial design using prospective, observational data from the Longitudinal Study of Australian Children, a representative, population-based prospective cohort study with biennial data collection from 2006 to 2018 with 8 years of follow-up (ages 6-7 to 14-15 years). Propensity score matching was used to ensure children with and without ADHD diagnosis were well matched on a wide range of variables, including hyperactive/inattentive (H/I) behaviors. Eligible children were born in 1999 to 2000 or 2003 to 2004 and did not have a previous ADHD diagnosis. All incident ADHD cases were matched with controls. Data were analyzed from July 2021 to January 2022.Incident parent-reported ADHD diagnosis at age 6 to 7, 8 to 9, 10 to 11, 12 to 13, or 14 to 15.P values calculated using bootstrapping to account for matching and repeat observations.Quality of life at age 14 to 15 was measured with Child Health Utility 9D (CHU9D) and 8 other prespecified, self-reported measures mapped to the World Health Organization’s QOL domains. Pooled regression models were fitted for each outcome, with 95% CIs and P = .10), general health , happiness , and peer trust . Diagnosed adolescents had worse psychological sense of school membership , academic self-concept , and self-efficacy ; displayed more negative social behaviors ; and were more likely to harm themselves  than adolescents without diagnosis.Of 8643 eligible children, a total of 393 adolescents had an ADHD diagnosis  and were age-, sex-, and H/I score–matched with 393 adolescents without ADHD diagnosis at time zero. Compared with adolescents without diagnosis, those with an ADHD diagnosis reported similar QOL on CHU9D (mean difference, −0.03; 95% CI, −0.07 to 0.01; In this cohort study, ADHD diagnosis was not associated with any self-reported improvements in adolescents’ QOL compared with adolescents with similar levels of H/I behaviors but no ADHD diagnosis. ADHD diagnosis was associated with worse scores in some outcomes, including significantly increased risk of self-harm. A large, randomized clinical trial with long-term follow-up is needed. This negative effect can extend beyond activities directly impacted by hyperactive or inattentive (H/I) behaviors, thus affecting overall quality of life (QOL).2 The World Health Organization (WHO) defines QOL as “an individual’s perception of their position in life,”3 placing emphasis on the subjective experience and the influence of the environment. Focusing on QOL when measuring impacts of a health condition provides an opportunity to shift away from symptom reduction toward more holistic, patient-centered outcomes.4Attention-deficit/hyperactivity disorder (ADHD) is “a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning…and negatively impacts…social and academic activities”2 Other studies found no association with QOL.6A 2017 industry-funded, systematic review found some evidence that pharmaceutical treatment of ADHD may be associated with improved QOL in short-term trials; however, this improvement is, at best, much smaller than for symptom reduction.7 H/I behaviors exist on a spectrum and correlate positively with impairment in domains, such as academic performance or socioemotional problems.8 Reducing them  can lead to some improvements in these domains.9 The potential for improvement is smaller for children with fewer H/I behaviors, for whom large reductions are impossible.10 For these children, harms associated with the ADHD diagnosis (such as stigma) or from treatment  may outweigh the benefits of symptom reduction.8It is unclear how much of the negative outcomes associated with ADHD in children can be attributed to impairment resulting from the condition itself and how much is due to the labeling effect of the ADHD diagnosis.12 Also, some argue that diagnosing (and treating) earlier in life may lead to better outcomes beyond symptom control.14 In contrast, a watch-and-wait approach favoring later diagnosis may avoid potential harms.15Gender and age are associated with ADHD diagnosis, H/I behaviors, and QOL, with girls being diagnosed with ADHD at much lower rates than boys.16 We hypothesized that children and adolescents benefit from an ADHD diagnosis and that this may result in better QOL among adolescents with diagnosis compared with youths with similar H/I behaviors and demographic characteristics but without ADHD diagnosis.The rationale for this study was to estimate the association of ADHD diagnosis with self-perceived QOL in adolescents. An ADHD diagnosis usually triggers intervention, either pharmacological or nonpharmacological, which should benefit the individual.We aimed to investigate whether an ADHD diagnosis in childhood or early adolescence is associated with improved QOL in adolescents compared with well-matched individuals without diagnosis. Additionally, we examined if any association of an ADHD diagnosis with QOL differed by sex, degree of H/I behaviors, or age at first diagnosis.STROBE) reporting guideline.This study was approved by The University of Sydney’s Human Ethics Research Committee. Informed consent was obtained when the children were recruited into the original cohort study. This study was conducted as a secondary analysis and did not directly recruit any participants. We followed the Strengthening the Reporting of Observational Studies in Epidemiology  and then emulated it18 as closely as possible, given the available observational data  and no years (time zero at age 14-15 years). As the contrast of interest18 was the observational analogue of an intention-to-treat effect, we did not account for crossover during follow-up (but we report it).We used a target trial approach to conceptualize an ideal pragmatic trial . We included data at age 4 to 5 years to determine preselection demographics for age 6 to 7 years.We used data from the Longitudinal Study of Australian Children (LSAC), a representative, population-based sample. A total of 4983 children were recruited into cohort 1 (born 1999-2000) and 5107 children into cohort 2 (born 2003-2004). Full details are published elsewhere.We restricted eligibility to children between the ages of 6 and 15, for whom data were available at age 6 to 7 years and with no reported ADHD diagnosis prior to age 6 years. At each subsequent wave, children either entered the exposure group if a new ADHD diagnosis was reported or the control group if they remained undiagnosed and were matched to a child in the exposure group .At each wave, children whose parents answered yes to the question “Does the study child have attention-deficit disorder or attention-deficit/ hyperactivity disorder?” for the first time were assigned to the exposure group. We used an optimal matching propensity score approach to select controls without a parent-reported ADHD diagnosis and paired them in a 1:1 ratio. We forced exact matching on sex to ensure equal numbers of boys and girls in each group.20 This validated screening instrument combines 5 Likert-scale items to create a score between 0 and 10, with higher scores signaling increasing risk of clinical ADHD.20Importantly, we included a measure of H/I behaviors in the propensity score, using the parent-reported H/I subscale of the Strengths and Difficulties Questionnaire (SDQ).21 advantage or disadvantage score, socioeconomic position z-score,22 mother’s education), and comorbidities . Aboriginal and/or Torres Strait Islander status was determined by asking parents the question “Is Study Child of Aboriginal or Torres Strait Islander origin?” with answer options no; yes, Aboriginal; yes, Torres Strait Islander; and yes, both. Children whose parents answered anything but no were determined to be of Aboriginal and/or Torres Strait Islander origin. Australian Indigenous children generally have worse health outcomes than non-Indigenous children, thus this was treated as a potential confounder for this analysis. The Socio-economic Advantage and Disadvantage score21 summarizes information about the economic and social conditions within an area, with lower scores indicating greater disadvantage and less advantage . The socioeconomic position z-score is a combination measure developed by LSAC researchers as an indicator of socioeconomic status.22 It measures parental education level, income, and occupational status and ranks each family in terms of their socioeconomic position relative to all other families in the sample,22 with higher values indicating relatively higher socioeconomic position .We conducted multiple imputations with fully conditional methods, creating 25 complete data sets with imputed values for all dependent and independent variables to account for missing data.Other variables in the propensity score were LSAC birth cohort, Aboriginal and/or Torres Strait Islander status, household features  location , socioeconomic indicators  as the primary outcome measure because it comprehensively measures QOL across 9 domains and is a preference-based tool, which has been found to be robust in both children and adolescents.25 Secondary outcome measures included academic self-concept, global health, negative social behaviors, overall happiness, peer trust, psychological sense of school membership, self-efficacy, and self-harm . Data were analyzed from July 2021 to January 2022.We first created 25 complete data sets using multiple imputation, then created 5 emulated trials (through propensity score matching at each age point) for each data set. We then pooled data across all emulated trials for all imputed data sets. We conducted linear regression analysis to estimate mean differences for 8 continuous outcomes and logistic regression to estimate an odds ratio for 1 binary outcome, including age at time zero as a design variable. To investigate potential modification, we constructed models that separately included interaction terms between ADHD diagnosis and H/I SDQ score, sex, and age at time zero. For this, we categorized the H/I SDQ variable into low (0-4), borderline (5-7), and high-risk (8-10) bands for clinically significant ADHD.A total of 393 adolescents with an ADHD diagnosis  were age-, sex-, and H/I score–matched with 393 adolescents without ADHD diagnosis . Propens28 Autism and depression or anxiety were above this threshold at 1 age each  and variance ratios of the propensity scores and of the individual variables  remained in the study at age 14 to 15 years, with some missing data for several variables at each age. We imputed data for all missing values (dependent and independent variables) and for participants lost to follow-up. Thus, we used data from all participants who were present at age 6 to 7 years, creating data sets with the same number of participants to select from at every age (8643 participants) (eTable 4 in the P = .10). There was no difference between groups in perceived health , happiness , or peer trust . On 4 other measures, adolescents with ADHD diagnosis reported worse outcomes than those without: they had lower academic self-concepts , more negative social behaviors , a worse sense of school membership , and less self-efficacy . The effect sizes, measured by Cohen d, for these 4 outcomes were all small  . In summary, among matched adolescents, an ADHD diagnosis was not associated with improved QOL but did have some negative associations, including an increase in risk of self-harm.4 However, to our knowledge, our study is the first that explicitly examined the association of the diagnosis with QOL. Other studies in this field have typically used clinically referred samples in which symptomatic participants with documented diagnoses are compared with controls without diagnosis and without symptoms, making it impossible to disentangle the effects of the disorder itself from those of the intervention in QOL.6 Previous intervention studies in this field have focused on medication rather than diagnosis, consequently only including participants with clinical ADHD diagnosis.5 Thus, our study expands the current knowledge that children with ADHD often experience reduced QOL by showing that at least some of this is associated with the diagnosis itself.Our results confirm those reported in other studies, finding that QOL is often lower in adolescents with ADHD compared with those without.29 Interestingly, parents of children with health issues tend to rate their children’s QOL lower than the children do themselves, while healthy children rate it lower than their parents do.29 Although this issue is beyond the scope of this study, we specifically designed our research to only include self-reported outcome measures to avoid bias due to parent reporting.While most studies in this field used parent-reported QOL, our findings align well with those that found smaller to no associations of ADHD with self-reported QOL measures.7 This is reflected in ADHD studies that have reported positive outcomes associated with diagnoses by creating a sense of empowerment and enablement as well as negative associations through disempowerment and stigma.8 We are not aware of research specifically on the association of the ADHD diagnostic label with QOL.Research on the impact of diagnostic labels in other conditions has found beneficial and harmful associations in several areas, such as psychosocial impact, support, future planning, behavior, and treatment expectations.9 However, it is also known that medication comes with numerous harms that may outweigh benefits, especially when combined with harms from the diagnosis and in children without major impairment, ie, those with few or borderline H/I behaviors.31 Still, studies suggest that even in children with subthreshold symptoms, impairment can occur, and they could benefit from additional support.33A diagnosis is usually a prerequisite for treatment, especially for pharmaceutical interventions. While there is limited evidence that ADHD medication increases QOL, research supports a general benefit of treatment on numerous related domains.8) may not be offset by benefits associated with the diagnosis or treatment. This is problematic, as it indicates that youths may be harmed by the diagnosis and that interventions to support them are not achieving the desired effect.Unfortunately, our results indicate no beneficial associations of an ADHD diagnosis with adolescents’ QOL, which is highly concerning. It implies that the harms associated with an ADHD label (such as stigma, prejudice, deflection from other problems, or the perceived inability to changeOur findings highlight the critical need for a large, well-designed, pragmatic trial to evaluate the long-term impact of an ADHD diagnosis on children’s and adolescents’ overall well-being. Moreover, accompanying qualitative research is also urgently needed to further investigate the lived experience of youths, especially their perceptions of benefits and harms associated with an ADHD diagnosis.These results also emphasize the requirement for a cautious clinical approach to ADHD diagnosis in children and adolescents, while underscoring the need for more targeted support to increase QOL in girls and in children with high-risk levels of H/I behaviors, whether diagnosed or not. Policy makers, researchers, and clinicians are urged to work together to develop more systemic solutions to overcome inequities in education and other settings that disadvantage youths because of their gender or neurodiversity, rather than solely relying on medicalizing and labeling them.18 The creation of 5 nested, emulated trials enabled us to avert selection bias and minimize confounding, increasing our confidence in the results. Moreover, we were able to draw on a large data set from a representative, population-based cohort study, with data from 8643 children covering 10 years, making our study results generalizable to the Australian population more broadly. The richness of the data set permitted us to closely match controls on an extensive range of covariates, minimizing confounding. Using multiple imputations enabled us to overcome problems with selection bias often inherent in longitudinal studies. Furthermore, we predetermined the exclusive use of self-reported outcome measures instead of parent-reported proxy measures, allowing us to capture the lived experience of adolescents themselves. Also, we specifically selected validated instruments to measure outcomes across all QOL aspects.A strength of our study is the explicit use of the target trial approach.Our study has some limitations. Importantly, while our approach emulates a target trial, we base our findings on observational, not randomized clinical trial data. As is the case with any observational analysis, we cannot be certain that our results are not influenced by residual confounding. We attempted to incorporate measures of all potential confounders into our propensity scores but were only able to rely on 1 proxy measure of H/I behaviors. A further limitation is study size: although the original data set was very large, the subset of youths with ADHD diagnosis and matched controls only incorporated 746 individuals. Especially for our modification subanalyses, this sample size may have been too small to detect differences.This cohort study found that adolescents with a prior ADHD diagnosis did not report better QOL at age 14 to 15 years compared with matched adolescents without diagnosis and with similar H/I behaviors. This raises important questions about the long-term effectiveness and safety of diagnosing children and adolescents with ADHD, especially for those with low-risk or borderline H/I behaviors. Our findings provide a rationale for a well-designed, large, randomized trial with long-term follow-up.


Ovocystatin has beneficial properties for cognitive function in young rats and might prevents aging-related cognitive impairment in older animals, as well as reduces memory decline in APP/PS1 mice model.Our study aimed at assessing the impact of ovocystatin on microglia activation and neurogenesis.Immunoactivation: Mouse wild type microglia were stimulated with ovocystatin at dose of 100 micrograms/ml. The effect of ovocystatin on nitric oxide production and interleukin 1 beta secretion were determined. Neurogenesis: Primary rat hippocampal neurons of H19-7 cell line was used. The impact of ovocystatin on proliferation, nitric oxide production, and expression of markers of neurogenesis: microtubule-associated protein 2  and Synapsin 1, were determined.It was shown that ovocystatin does not stimulate microglial cells to produce inflammatory mediators. Whereas, no toxic effect of ovocystatin (1-100 ug/ml) on H19-7 cells viability, and dose-dependent down-regulation of proliferation were demonstrated. It was also shown that in primary hippocampal neurons of H19-7 cells incubated with ovocystatin (100 micrograms/ml), the expression level of MAP2 C/D (75kDa) - characteristic form of immature neurons is unchanged. However, the increased expression of MAP2 A/B protein (280 kDa) – characteristic for mature neurons was observed after 6 and 24h incubation with ovocystatin. Relatively to MAP2 A/B, increased expression of synapsin 1 was observed.The ovocystatin might be a potential activator of molecular mechanisms in primary hippocampal neurons, participating in regulation of neurogenesis. Nevertheless, further studies are needed.No significant relationships.