How socio-political change is associated with the number of individually reported negative life events: a population-based study using the German reunification 1989/1990 as an example.

BACKGROUND: Socio-political change often leads to disruptions in employment and social networks, which can exacerbate health issues and increase mortality rates. These consequences are likely observed as an increase in negative life events (NLEs), serving as indicators of the broader social and health impacts. Using the German reunification in 1989/1990 as an example, this study investigates changes in reported numbers of NLEs and differences regarding sociodemographic characteristics. METHODS: We used data from the population-based Study of Health in Pomerania (SHIP-START-0, SHIP-Life-Events and Gene-Environment Interaction in Depression; N=1932). Numbers of NLEs in different categories (work/financial, social/interpersonal, illness (own) and illness/death (others)) were measured retrospectively in 5-year intervals (1980-2004) using a semistructured interview. Pre-reunification and post-reunification changes were modelled using piecewise mixed-effects Poisson regressions with the 1990-1994 interval (reunification) as change point. Interactions with age, sex and education were examined. RESULTS: The number of most NLE categories, except social/interpersonal NLEs, increased at reunification. Whereas work/financial NLEs slightly decreased post-reunification, illness-related NLEs continued to increase. Higher numbers of social/interpersonal NLEs were found with younger age. More illness-related NLEs were reported with older age, lower education (illness (own)) and by women (illness/death (others)). However, the majority reported no NLEs at reunification (68.2%-80.7%, varying by category). CONCLUSION: Our findings suggest that although some individuals experience a marked increase in NLEs due to socio-political changes, many remain unaffected, emphasising the need for a differentiated understanding of these effects. This increase in NLEs may partly account for ongoing health and well-being disparities among countries with differing transformation histories.

Treatment of adult attention-deficit hyperactivity disorder (ADHD) with transcranial direct current stimulation (tDCS): study protocol for a parallel, randomized, double-blinded, sham-controlled, multicenter trial (Stim-ADHD).

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation treatment used as an alternative or complementary treatment for various neuropsychiatric disorders, and could be an alternative or add-on therapy to psychostimulants in attention-deficit hyperactivity disorder (ADHD). Previous studies provided some evidence for improvements in cognition and clinical symptoms in pediatric and adult ADHD patients. However, data from multi-center randomized controlled trials (RCTs) for this condition are lacking. Thus, our aim is to evaluate short- and mid-term effects of tDCS in this multi-center, randomized, double blind, and sham-controlled, parallel group clinical trial with a 1:1 randomization ratio. Primary endpoint is the total score of DSM-IV scale of the internationally established Conners' Adult ADHD Rating Scales (German self-report screening version, CAARS-S-SR), at day 14 post-intervention (p.i.) to detect short-term lasting effects analyzed via analyses of covariance (ANCOVAs). In case of significant between-groups differences at day 14 p.i., hierarchically ordered hypotheses on mid-term lasting effects will be investigated by linear mixed models with visit (5 time points), treatment, treatment by visit interaction, and covariates as fixed categorical effects plus a patient-specific visit random effect, using an unstructured covariance structure to model the residual within-patient errors. Positive results of this clinical trial will expand the treatment options for adult ADHD patients with tDCS and provide an alternative or add-on therapy to psychostimulants with a low risk for side effects.Trial Registration The trial was registered on July 29, 2022 in the German Clinical Trials Register (DRKS00028148).

Explorative analyses on spatial differences in the desire for social distance toward people with mental illness in a diverging city.

Introduction: Stigma is an individual and societal process based on attitudes and power and relates to both spatial disparities and social distinction. In this study, we examined differences in desire for social distance toward people with mental illness within a city using social and spatial information. Methods: ANOVAs and Scheffé post-hoc tests analyzed varying desires for social distance toward people with mental illness within Leipzig (East Germany). Joint Correspondence Analyses (JCA) explored correspondences between desire for social distance, socio-economic status, age, life orientation, social support, duration of living in Leipzig, and shame toward having a mental illness in five city districts of Leipzig in LIFE study participants (by Leipzig Research Center for Civilization Disease, data collected 2011-2014 and 2018-2021, n = 521). Results: Stigma varied among Leipzig's districts (F(df = 4) = 4.52, p = 0.001). JCAs showed that a higher desired social distance toward people with mental illness corresponded with spatial differences, high levels of pessimism, high shame of being mentally ill, low social support, low socio-economic status, and older age (75.74 and 81.22% explained variances). Conclusion: In terms of stigma, where people with mental illness live matters. The results identified target groups that should be addressed by appropriate intervention and prevention strategies for mental health care.

[Life events related to the German reunification and their associations with psychosocial health in a sample of northeast Germany]. / Nach-Wende-Ereignisse und deren Assoziation mit psychosozialer Gesundheit in einer nordostdeutschen Stichprobe.

Objectives: The aim of the present study was to investigate (1) the type and frequency of reported life events of the East German population related to the German reunification and (2) their associations with psychosocial health. Methods: Data of 2247 participants of the Study of Health in Pomerania was used.These qualitative responses were analysed using quantitative content analysis. Their associations with subjective physical and mental health, optimism, social support, depressive symptoms, and chronic stress were examined. Results: Eight life event categories were identified (education, employment-related changes, material changes, new opportunities, personal life events, politics, separations, reunifications). Especially, experiencing new opportunities was associated with a higher level of optimism as well as a lower level of depressive symptoms and chronic stress. Conclusions: In this study, events frequently described in the literature (e.g., employment-related and social changes) were confirmed and systematized.The observed associations of these events with psychosocial factors should be examined further in future studies.

Mental resources, mental health and sociodemography: a cluster analysis based on a representative population survey in a large German city.

BACKGROUND: Mental resources such as optimism and social support are important to face different stressors. The aim of this study is to identify groups in the population that are similar in terms of their mental resources. METHODS: For this purpose, a randomly selected general population community sample was used, representative for the city of Leipzig, Germany. In a two-stage process, three clusters were identified using hierarchical cluster analysis and the K-means method and then tested with a multinomial logistic regression analysis for differences in sociodemographic characteristics. RESULTS: Three clusters were identified which vary in their extent of social support and optimism. In distinguishing between those with higher and lower (medium or poor) mental resources, male gender, unemployment, being born abroad and low household income are risk factors for having fewer mental resources. Internal migrants from West Germany and persons with children at home have a higher chance of being in the type with good mental resources. The groups with medium and lower mental resources differ significantly only by variables living with a partner and employment. CONCLUSION: Our results indicate that good mental resources are associated with good mental health. Special mental health care programs, focusing in particular on the needs of vulnerable groups with poor mental resources within a society, should be implemented.

Historical and regional particularities in the prevalence of traumatic events and posttraumatic stress disorder in East and West Germany.

BACKGROUND: Epidemiological research on the prevalence of traumatic events and PTSD has shown that there are significant differences between countries, due to their different history and socialization processes. In the case of Germany, this is particularly relevant. Germany was divided into two states from 1949 to 1990. This study examines the prevalence of traumatic events and PTSD in the formerly divided East and West Germany. METHODS: For the prevalence of traumatic events, we used data from four representative surveys (years 2005, 2007, 2008, and 2016) with a total of N = 9,200 respondents. For the analyses of PTSD prevalence, we used data from three representative surveys (years 2005, 2007, 2008) with a total of N = 6676 respondents. We compared different birth cohorts, persons living in the former West vs. East Germany, and the application of different diagnostic criteria using a chi-square test. RESULTS: The overall one-month prevalence rate for PTSD was 3.4% (3.0% for men and 3.8% for women). We found significant differences in the occurrence of traumatic events between genders, different age cohorts as well as between people who live in East and West Germany. Significant differences in the prevalence of PTSD can only be observed for different age cohorts. Most of the age effects are due to traumatic events related to World War II (WWII). Prevalence rates for PTSD were higher when the diagnostic criterions of the DSM-V were applied compared to the criterions of the DSM-IV. CONCLUSIONS: Our data suggests that socio-political factors may need to be considered when accounting for differences in occurrence rates of traumatic events, but not for prevalence rates of PTSD, between East and West Germany. People who have experienced WW II have a higher risk of suffering from PTSD. Future epidemiological trauma research should take historical and regional peculiarities of countries into account.

An explorative cross-sectional analysis of mental health shame and help-seeking intentions in different lifestyles.

To identify und support particular target groups for mental health prevention, we explore the links between shame and help-seeking intentions concerning mental health in different lifestyles (based on socioeconomic status as well as health-related behaviors). Lifestyles were operationalized by nine confirmatory, homogenous clusters of the sample. These clusters are based on individuals' similarities in sociodemographic aspects and health behavior. Analyses included t tests, Chi-square, ANOVA, regressions investigating in sociodemographic characteristics. Hierarchical linear models examining cross-sectional associations of shame and willingness to seek help for different lifestyles of participants of the Study of Health in Pomerania (SHIP-START-1 and SHIP-START-3, data collected 2002-2006 and 2014-2016; n = 1630). Hierarchical linear models showed small context effects for lifestyle-related associations of shame and willingness to seek help. For younger as well as male participants, lifestyles indicated different associations of shame and help-seeking intentions: Especially the lifestyles with unhealthy behaviors and high as well as low socioeconomic status resulted in higher shame being associated with low help-seeking intentions in case of mental illness. Lifestyle clusters might be a useful tool to identify marginalized groups with unhealthy behaviors, which should be addressed by interventions and prevention programs.

[Sex- and Regionalspecific Differences in Child Abuse and Violence Before the German Reunification. Results from GESA, a Multi-Cohort Study]. / Geschlechts- und regionalspezifische Unterschiede von Kindesvernachlässigung und Gewalt vor der deutschen Wiedervereinigung. Ergebnisse aus GESA, einem Multi-Kohorten Konsortium.

Results from a population-based study suggest sex-specific patterns of self-reported child maltreatment, more frequently reported in former West than East Germany. Aim of the current study was to examine these patterns in two regional samples of the former East- (SHIP, 2008 - 2012) and West German (KORA, 2013 - 2014) population. Child maltreatment was assessed using the Childhood Trauma Screener (CTS). Overall, child maltreatment was less often reported in the East German sample, compared to the West German sample. The most prominent differences were identified in self-rated emotional violence (east 6.1%, west 8.7%), physical violence (east 5.7%, west 10.3%) and physical neglect (east 10.0%, west 19.2%). However, we could not find differences in sex-specific patterns between the East and West German samples. Results were discussed within a historical context, since the events took place before the German reunification in two oppose political systems.

Association between Individual Norepinephrine Transporter (NET) Availability and Response to Pharmacological Therapy in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD).

BACKGROUND: The role of the norepinephrine transporter (NET) has received increased focus in recent studies on the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). The predictive value for pharmacological treatment and its link to other health or social limitations has been little-studied. This follow-up research on adult patients with ADHD aimed to explore whether the therapy response and health and social impairments depend on baseline individual NET availability. METHODS: Data were collected from 10 patients on personal, family and professional situations, mental and physical health and treatments received after baseline via online and telephone surveys and were compared to baseline data to evaluate treatment-related changes. RESULTS: The majority of our ADHD patients did not show therapy responses but showed improvements due to pharmacological treatment. There was no evidence of relationships between pre-treatment NET availability and therapy response or health/social limitations. CONCLUSIONS: Pharmacological monotherapy was insufficient to promote symptom remission, especially for participants with extreme insufficiency in NET availability, but improved outcomes in academic and social functioning. Psychotherapy should be considered as an add-on to the standard treatment approach due to its positive outcome in reducing social limitations. The prognostic value of individual NET availability in predicting the response to therapy needs further studies with large sample sizes.

The Big Five Personality Traits and Brain Arousal in the Resting State.

Based on Eysenck's biopsychological trait theory, brain arousal has long been considered to explain individual differences in human personality. Yet, results from empirical studies remained inconclusive. However, most published results have been derived from small samples and, despite inherent limitations, EEG alpha power has usually served as an exclusive indicator for brain arousal. To overcome these problems, we here selected N = 468 individuals of the LIFE-Adult cohort and investigated the associations between the Big Five personality traits and brain arousal by using the validated EEG- and EOG-based analysis tool VIGALL. Our analyses revealed that participants who reported higher levels of extraversion and openness to experience, respectively, exhibited lower levels of brain arousal in the resting state. Bayesian and frequentist analysis results were especially convincing for openness to experience. Among the lower-order personality traits, we obtained the strongest evidence for neuroticism facet 'impulsivity' and reduced brain arousal. In line with this, both impulsivity and openness have previously been conceptualized as aspects of extraversion. We regard our findings as well in line with the postulations of Eysenck and consistent with the recently proposed 'arousal regulation model'. Our results also agree with meta-analytically derived effect sizes in the field of individual differences research, highlighting the need for large (collaborative) studies.

Stigma as a barrier to addressing childhood trauma in conversation with trauma survivors: A study in the general population.

Victims of childhood trauma report shame and anticipation of stigma, leading to non-disclosure and avoidance of help. Stigma is potentially aggravating the mental health consequences of childhood trauma. So far there is no comprehensive study examining stigma toward adult survivors of various forms of childhood trauma, and it is unclear whether stigma interferes with reaching out to affected individuals. In a vignette study based on a representative sample of the German general population (N = 1320; 47.7% male) we randomly allocated participants to brief case vignettes pertaining to past childhood sexual/physical abuse or accidents, and adult physical abuse. Stigma was elicited by applying the Social Distance Scale, assessing respondents' attitudes/stereotypes toward the persons in the vignette and their reluctance to address the specific trauma in conversation. While one aim was to establish the prevalence of stigma toward persons with CT, we hypothesized that attitudes differ according to type of trauma. Of the respondents, 45% indicated they were unlikely to reach out to a victim of childhood sexual abuse, 38% to a victim of childhood physical abuse, 31% to someone reporting a childhood accident and 25% to someone reporting adult physical abuse. Contrary to our expectations, childhood sexual abuse did not consistently elicit more stigma than childhood physical abuse in Krukall-Wallis tests. Equally, childhood interpersonal trauma did not consistently elicit more stigma than childhood accidental trauma. Structural equation modeling revealed social distance as mediator of the relationship between negative stereotypes and reluctance to address childhood trauma in conversation. Our analyses further revealed an ambiguous role of negative stereotypes in addressing childhood trauma in conversation with trauma victims, which has yet to be examined. There is evidence for stigma associated with having survived childhood trauma, which is interfering with offering help.

The relation between childhood adversity and adult obesity in a population-based study in women and men.

Childhood maltreatment has been shown to relate to adult obesity. In this epidemiological study, we investigate the association between childhood maltreatment and waist-to-height-ratio (WHtR) in a sample of the German adult population, comprising of N = 2936 participants. WHtR, an indicator for risk of obesity, was the primary outcome. Childhood maltreatment was assessed by the Childhood Trauma Screener (CTS), which assesses emotional and physical neglect, abuse as well as sexual abuse. Cohort-data were harmonized and analyzed within DataSHIELD. We used multivariable regression models to estimate the association of childhood maltreatment and WHtR at different levels of adjustments for potential confounders. Overall childhood maltreatment was associated with a higher WHtR in both sexes (women: p = 0.004, men: p < 0.001); associations were no longer significant in women after adding socioeconomic variables, but remained significant in men (p = 0.013). Additionally, we were able to identify sex specific patterns for childhood maltreatment predicting the WHtR. Emotional neglect and abuse had stronger impacts on the WHtR in women than in men, whereas physical neglect and abuse had stronger impacts in men. To our knowledge, this is the first comprehensive population-based study testing various types of childhood maltreatment with WHtR in sex-, region- and weight-stratified analyses. Future studies in clinical populations are warranted to examine U-shaped correlations between increased WHtR and childhood maltreatment.

The interplay of gender, social context, and long-term unemployment effects on subjective health trajectories.

BACKGROUND: While a strong negative impact of unemployment on health has been established, the present research examined the lesser studied interplay of gender, social context and job loss on health trajectories. METHODS: Data from the German Socio-Economic Panel was used, which provided a representative sample of 6838 participants. Using latent growth modelling the effects of gender, social context (East vs. West Germans), unemployment (none, short-term or long-term), and their interactions were examined on health (single item measures of self-rated health and life satisfaction respectively). RESULTS: Social context in general significantly predicted the trajectories of self-rated health and life satisfaction. Most notably, data analysis revealed that West German women reported significantly lower baseline values of self-rated health following unemployment and did not recover to the levels of their East German counterparts. Only long-term, not short-term unemployment was related to lower baseline values of self-rated health, whereas, in relation to baseline values of life satisfaction, both types of unemployment had a similar negative effect. CONCLUSIONS: In an economic crisis, individuals who already carry a higher burden, and not only those most directly affected economically, may show the greatest health effects.

The "VIP-ADHD trial": Does brain arousal have prognostic value for predicting response to psychostimulants in adult ADHD patients?

EEG studies have shown that adult ADHD patients have less stable brain arousal regulation than age and gender matched controls. Psychostimulants have brain arousal stabilising properties evident in EEG patterns. The aim of this study was to investigate whether the stability of brain arousal regulation has prognostic value in predicting response to methylphenidate therapy in adult ADHD patients. In an open-label, single-arm, multi-centre, confirmatory trial, 121 adult ADHD patients were recruited and 112 qualified for the full analysis set. All participants received an initial dose of 20 mg extended release methylphenidate at baseline. After a titration phase of up to 4 weeks, patients remained on a weight-based target dose of extended release methylphenidate for 4 weeks. Using the Vigilance Algorithm Leipzig (VIGALL 2.1), we assessed brain arousal regulation before the treatment with methylphenidate, based on a 15-min EEG at quiet rest recorded at baseline. Using automatic stage-classification of 1 s segments, we computed the mean EEG-vigilance (indexing arousal level) and an arousal stability score (indexing arousal regulation). The primary endpoint was the association between successful therapy, defined by a 30% reduction in CAARS, and stable/unstable brain arousal. 52 patients (46%) showed an unstable brain arousal regulation of which 23% had therapy success. In the stable group, 35% had therapy success, implying an absolute difference of 12 percentage points (95% CI -5 to 29, p = 0.17) in the direction opposite to the hypothesized one. There were no new findings regarding the tolerability and safety of extended release methylphenidate therapy.

Fatigue and brain arousal in patients with major depressive disorder.

Fatigue is considered a key symptom of major depressive disorder (MDD), yet the term lacks specificity. It can denote a state of increased sleepiness and lack of drive (i.e., downregulated arousal) as well as a state of high inner tension and inhibition of drive with long sleep onset latencies (i.e., upregulated arousal), the latter typically found in depression. It has been proposed to differentiate fatigue along the dimension of brain arousal. We investigated whether such stratification within a group of MDD patients would reveal a subgroup with distinct clinical features. Using an automatic classification of EEG vigilance stages, an arousal stability score was calculated for 15-min resting EEGs of 102 MDD patients with fatigue. 23.5% of the patients showed signs of hypoarousal with EEG patterns indicating drowsiness or sleep; this hypoaroused subgroup was compared with remaining patients (non-hypoaroused subgroup) concerning self-rated measures of depressive symptoms, sleepiness, and sleep. The hypoaroused subgroup scored higher on the Beck Depression Inventory items "loss of energy" (Z = - 2.13, p = 0.033; ɳ2 = 0.044, 90% CI 0.003-0.128) and "concentration difficulty" (Z = - 2.40, p = 0.017; ɳ2 = 0.056, 90% CI 0.009-0.139), and reported higher trait and state sleepiness (p < 0.05) as compared to the non-hypoaroused group. The non-hypoaroused subgroup, in contrast, reported more frequently the presence of suicidal ideation (Chi2 = 3.81, p = 0.051; ɳ2 = 0.037, 90% CI 0.0008-0.126). In this study, we found some evidence that stratifying fatigued MDD patients by arousal may lead to subgroups that are pathophysiologically and clinically more homogeneous. Brain arousal may be a worth while target in clinical research for better understanding the mechanisms underlying suicidal tendencies and to improve treatment response.

Gender differences in adult ADHD: Cognitive function assessed by the test of attentional performance.

INTRODUCTION: The aim of this study was to assess cognitive differences between male and female adults with Attention Deficit Hyperactivity Disorder (ADHD). METHODS: Patients with an ADHD diagnosis according to the DSM-IV guidelines were included in a cross-sectional study evaluating cognitive measures. 28 women and 41 men from ages 19 to 56 completed self-report questionnaires and performed a computer-based test of attentional performance (TAP). The TAP assesses cognitive functions highly affected in ADHD patients, including working memory, alertness and attention as well as behavioral control and response inhibition. RESULTS: There were no measurable differences in self-report scales assessing current symptomology between the sexes, however men scored higher on the scale for childhood symptoms. Performance measures for general wakefulness were comparable between men and women, while working memory and behavioral control test results differed. Females reacted significantly slower and more unstable for both the TAP Go/NoGo paradigm and working memory subtest, while also making more errors in the latter. CONCLUSIONS: We found gender-specific effects regarding working memory and behavioral control in this sample of adult patients with ADHD. Further studies are warranted, examining whether these differences relate to differences in clinical presentation and comorbidity patterns between men and women.

Fatigue in Cancer and Neuroinflammatory and Autoimmune Disease: CNS Arousal Matters.

The term fatigue is not only used to describe a sleepy state with a lack of drive, as observed in patients with chronic physical illnesses, but also a state with an inhibition of drive and central nervous system (CNS) hyperarousal, as frequently observed in patients with major depression. An electroencephalogram (EEG)-based algorithm has been developed to objectively assess CNS arousal and to disentangle these pathophysiologically heterogeneous forms of fatigue. The aim of this study was to test the hypothesis that fatigued patients with CNS hyperarousal score higher on depressive symptoms than those without this neurophysiological pattern. METHODS: Subjects with fatigue (Multidimensional Fatigue Inventory sum-score > 40) in the context of cancer, neuroinflammatory, or autoimmune diseases were drawn from the 60+ cohort of the Leipzig Research Center for Civilization Diseases. CNS arousal was assessed by automatic EEG-vigilance stage classification using the Vigilance Algorithm Leipzig (VIGALL 2.1) based on 20 min EEG recordings at rest with eyes closed. Depression was assessed by the Inventory of Depressive Symptomatology (IDS-SR). RESULTS: Sixty participants (33 female; median age: 67.5 years) were included in the analysis. As hypothesized, fatigued patients with CNS hyperarousal had higher IDS-SR scores than those without hyperarousal (F1,58 = 18.34; p < 0.0001, η2 = 0.240). CONCLUSION: hyperaroused fatigue in patients with chronic physical illness may be a sign of comorbid depression.

Is brain arousal regulation a predictor of response to psychostimulant therapy in adult ADHD patients?

We investigated whether baseline brain arousal instability during resting state EEG, using the Vigilance Algorithm Leipzig (VIGALL 2.1), can predict response to methylphenidate therapy in adult ADHD patients. An arousal stability score of the EEGs of 28 adult ADHD patients was calculated quantifying the extent of arousal decline. In logistic regression analysis, arousal stability score predicted response to MPH [odds ratio 1.28 (95% CI 1.0-1.65); p = 0.027]. In this pilot study, we demonstrated that arousal stability at baseline predicted methylphenidate treatment response, indicating that less stable arousal regulation during a 15-min EEG at rest increases the chance of treatment response.

Vulnerability to bipolar disorder is linked to sleep and sleepiness.

Sleep impairments are a hallmark of acute bipolar disorder (BD) episodes and are present even in the euthymic state. Studying healthy subjects who are vulnerable to BD can improve our understanding of whether sleep impairment is a predisposing factor. Therefore, we investigated whether vulnerability to BD, dimensionally assessed by the hypomanic personality scale (HPS), is associated with sleep disturbances in healthy subjects. We analyzed participants from a population-based cohort who had completed the HPS and had either a 7-day actigraphy recording or a Pittsburgh sleep quality index (PSQI) assessment. In addition, subjects had to be free of confounding diseases or medications. This resulted in 771 subjects for actigraphy and 1766 for PSQI analyses. We found strong evidence that higher HPS scores are associated with greater intraindividual sleep variability, more disturbed sleep and more daytime sleepiness. In addition, factor analyses revealed that core hypomanic features were especially associated with self-reported sleep impairments. Results support the assumption of disturbed sleep as a possibly predisposing factor for BD and suggest sleep improvement as a potential early prevention target.

Adult attention-deficit/hyperactivity disorder is associated with reduced norepinephrine transporter availability in right attention networks: a (S,S)-O-[11C]methylreboxetine positron emission tomography study.

The norepinephrine transporter (NET) has been suggested to play a critical role in attention-deficit/hyperactivity disorder (ADHD). In this prospective controlled study we tested the a-priori-hypothesis that central NET availability is altered in adult ADHD patients compared to healthy controls. Study participants underwent single positron emission tomography-magnetic resonance imaging (PET-MRI). MRI sequences included high resolution T1-MPRAGE data for regions of interest (ROI) delineation and voxel-based morphometry (VBM) and T2-weighted fluid-attenuated inversion-recovery for detection and exclusion of pathological abnormalities. NET availability was assessed by NET-selective (S,S)-O-[11C]methylreboxetine; regional distribution volume ratios (DVR) were calculated based on individual PET-MRI data co-registration and a multi-linear reference tissue model with two constraints (MRTM2; reference region: occipital cortex). VBM analysis revealed no difference in local distribution of gray matter between the 20 ADHD patients (9 females, age 31.8 ± 7.9 years, 488 ± 8 MBq injected activity) and the 20 age-matched and sex-matched control participants (9 females, age 32.3 ± 7.9 years, 472 ± 72 MBq). In mixed-model repeated-measures analysis with NET availability as dependent and ROI as repeated measure we found a significant main effect group in fronto-parietal-thalamic-cerebellar regions (regions on the right: F1,25 = 12.30, p = .002; regions on the left: F1,41 = 6.80, p = .013) indicating a reduced NET availability in ADHD patients. None of the other investigated brain regions yielded significant differences in NET availability between groups after applying a Benjamini-Hochberg correction at a significance level of 0.05. Overall our findings demonstrate the pathophysiological involvement of NET availability in adult ADHD.