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).

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.

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.

[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.

[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.

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.

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.

Human brain arousal in the resting state: a genome-wide association study.

Arousal affects cognition, emotion, and behavior and has been implicated in the etiology of psychiatric disorders. Although environmental conditions substantially contribute to the level of arousal, stable interindividual characteristics are well-established and a genetic basis has been suggested. Here we investigated the molecular genetics of brain arousal in the resting state by conducting a genome-wide association study (GWAS). We selected N = 1877 participants from the population-based LIFE-Adult cohort. Participants underwent a 20-min eyes-closed resting state EEG, which was analyzed using the computerized VIGALL 2.1 (Vigilance Algorithm Leipzig). At the SNP-level, GWAS analyses revealed no genome-wide significant locus (p < 5E-8), although seven loci were suggestive (p < 1E-6). The strongest hit was an expression quantitative trait locus (eQTL) of TMEM159 (lead-SNP: rs79472635, p = 5.49E-8). Importantly, at the gene-level, GWAS analyses revealed significant evidence for TMEM159 (p = 0.013, Bonferroni-corrected). By mapping our SNPs to the GWAS results from the Psychiatric Genomics Consortium, we found that all corresponding markers of TMEM159 showed nominally significant associations with Major Depressive Disorder (MDD; 0.006 ≤ p ≤ 0.011). More specifically, variants associated with high arousal levels have previously been linked to an increased risk for MDD. In line with this, the MetaXcan database suggests increased expression levels of TMEM159 in MDD, as well as Autism Spectrum Disorder, and Alzheimer's Disease. Furthermore, our pathway analyses provided evidence for a role of sodium/calcium exchangers in resting state arousal. In conclusion, the present GWAS identifies TMEM159 as a novel candidate gene which may modulate the risk for psychiatric disorders through arousal mechanisms. Our results also encourage the elaboration of the previously reported interrelations between ion-channel modulators, sleep-wake behavior, and psychiatric disorders.

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.

Brain arousal regulation and depressive symptomatology in adults with attention-deficit/hyperactivity disorder (ADHD).

BACKGROUND: The aim of the present study was to evaluate the stability of brain arousal in adult attention-deficit/hyperactivity disorder (ADHD) outpatients with and without depressive symptomatology, and its association with depressive symptom severity and absolute electroencephalogram (EEG) power in different frequency bands. METHODS: We included 31 outpatient adults (45.16% females), who were diagnosed according to DSM-IV and received no medication. Their arousal stability score (index of the steepness of arousal decline during a 15-min EEG under resting conditions), the absolute EEG power and self-reports, including depressive and ADHD-related symptoms, were analyzed. Participants were split into an unstable and stable arousal group based on the median (= 6) of the arousal stability score. RESULTS: ADHD patients in the stable group reported more severe depressive symptoms (p = 0.018) and showed reduced absolute EEG power in the delta (0.002 ≤ p ≤ 0.025) and theta (0.011 ≤ p ≤ 0.034) bands compared to those in the unstable group. There was no correlation between the arousal stability score and self-report-scales concerning ADHD-related symptoms (0.214 ≤ p ≤ 0.989), but a positive association with self-reported depressive severity (p = 0.018) and negative association with powers in the EEG delta and theta bands (0.001 ≤ p ≤ 0.033). CONCLUSIONS: In view of high comorbidity of depression and ADHD in adult patients, these findings support the assumption that brain arousal regulation could be considered as a helpful marker for the clinical differentiation between ADHD and depression.

Impact of brain arousal and time-on-task on autonomic nervous system activity in the wake-sleep transition.

BACKGROUND: Autonomic nervous system (ANS) activity has been shown to vary with the state of brain arousal. In a previous study, this association of ANS activity with distinct states of brain arousal was demonstrated using 15-min EEG data, but without directly controlling for possible time-on-task effects. In the current study we examine ANS-activity in fine-graded EEG-vigilance stages (indicating states of brain arousal) during two conditions of a 2-h oddball task while controlling for time-on-task. In addition, we analyze the effect of time-on-task on ANS-activity while holding the level of brain arousal constant. METHODS: Heart rate and skin conductance level of healthy participants were recorded during a 2-h EEG with eyes closed under simultaneous presentation of stimuli in an ignored (N = 39) and attended (N = 39) oddball condition. EEG-vigilance stages were classified using the Vigilance Algorithm Leipzig (VIGALL 2.1). The time-on-task effect was tested by dividing the EEG into four 30-min consecutive time blocks. ANS-activity was compared between EEG-vigilance stages across the entire 2 h and within each time block. RESULTS: We found a coherent decline of ANS-activity with declining brain arousal states, over the 2-h recording and in most cases within each 30-min block in both conditions. Furthermore, we found a significant time-on-task effect on heart rate, even when arousal was kept constant. It was most pronounced between the first and all subsequent blocks and could have been a consequence of postural change at the beginning of the experiment. CONCLUSION: Our findings contribute to the validation of VIGALL 2.1 using ANS parameters in 2-h EEG recording under oddball conditions.

Evoked potentials and behavioral performance during different states of brain arousal.

BACKGROUND: Previous studies compared evoked potentials (EPs) between several sleep stages but only one uniform wake state. However, using electroencephalography (EEG), several arousal states can be distinguished before sleep onset. Recently, the Vigilance Algorithm Leipzig (VIGALL 2.0) has been developed, which automatically attributes one out of seven EEG-vigilance stages to each 1-s EEG segment, ranging from stage 0 (associated with cognitively active wakefulness), to stages A1, A2 and A3 (associated with relaxed wakefulness), to stages B1 and B2/3 (associated with drowsiness) up to stage C (indicating sleep onset). Applying VIGALL, we specified the effects of these finely differentiated EEG-vigilance stages (indicating arousal states) on EPs (P1, N1, P2, N300, MMN and P3) and behavioral performance. Subjects underwent an ignored and attended condition of a 2-h eyes-closed oddball-task. Final analysis included 43 subjects in the ignored and 51 subjects in the attended condition. First, the effect of brain arousal states on EPs and performance parameters were analyzed between EEG-vigilance stages A (i.e. A1, A2 and A3 combined), B1 and B2/3&C (i.e. B2/3 and C combined). Then, in a second step, the effects of the finely differentiated EEG-vigilance stages were further specified. RESULTS: Comparing stages A versus B1 versus B2/3&C, a significant effect of EEG-vigilance stages on all behavioral parameters and all EPs, with exception of MMN and P3, was found. By applying VIGALL, a more detailed view of arousal effects on EP and performance was possible, such as the finding that the P2 showed no further significant increase in stages deeper than B1. Stage 0 did not differ from any of the A-stages. Within more fine-graded stages, such as the A-substages, EPs and performance only partially differed. However, these analyses were partly based on small sample sizes and future studies should take effort to get enough epochs of rare stages (such as A3 and C). CONCLUSIONS: A clear impact of arousal on EPs and behavioral performance was obtained, which emphasize the necessity to consider arousal effects when interpreting EPs.

Early report on brain arousal regulation in manic vs depressive episodes in bipolar disorder.

OBJECTIVES: The arousal regulation model of affective disorders attributes an important role in the pathophysiology of affective disorders to dysregulation of brain arousal regulation. According to this model, sensation avoidance and withdrawal in depression and sensation seeking and hyperactivity in mania can be explained as auto-regulatory attempts to counteract a tonically high (depression) or unstable (mania) arousal. The aim of this study was to compare brain arousal regulation between manic and depressive bipolar patients and healthy controls. We hypothesized that currently depressed patients with bipolar disorder show hyperstable arousal regulation, while currently manic patients show unstable arousal regulation. METHODS: Twenty-eight patients with bipolar disorder received a 15-min resting electroencephalogram (EEG) during a depressive episode and 19 patients received the same during a manic/hypomanic episode. Twenty-eight healthy control subjects were matched for age and sex. The Vigilance Algorithm Leipzig (VIGALL), which classifies 1-s EEG segments as one of seven EEG-vigilance substages, was used to measure brain arousal regulation. RESULTS: Manic patients showed more unstable EEG-vigilance regulation as compared to the control sample (P = .004) and to patients with a depressive episode (P ≤ .001). Depressive patients had significantly higher mean vigilance levels (P = .045) than controls. CONCLUSIONS: A clear difference was found in the regulation of brain arousal of manic patients vs depressive patients and controls. These data suggest that brain arousal might depend on the current mood state, which would support the arousal regulation model of affective disorders.

Genome-wide association analysis of actigraphic sleep phenotypes in the LIFE Adult Study.

The genetic basis of sleep is still poorly understood. Despite the moderate to high heritability of sleep-related phenotypes, known genetic variants explain only a small proportion of the phenotypical variance. However, most previous studies were based solely upon self-report measures. The present study aimed to conduct the first genome-wide association (GWA) of actigraphic sleep phenotypes. The analyses included 956 middle- to older-aged subjects (40-79 years) from the LIFE Adult Study. The SenseWear Pro 3 Armband was used to collect 11 actigraphic parameters of night- and daytime sleep and three parameters of rest (lying down). The parameters comprised measures of sleep timing, quantity and quality. A total of 7 141 204 single nucleotide polymorphisms (SNPs) were analysed after imputation and quality control. We identified several variants below the significance threshold of P ≤ 5× 10-8 (not corrected for analysis of multiple traits). The most significant was a hit near UFL1 associated with sleep efficiency on weekdays (P = 1.39 × 10-8 ). Further SNPs were close to significance, including an association between sleep latency and a variant in CSNK2A1 (P = 8.20 × 10-8 ), a gene known to be involved in the regulation of circadian rhythm. In summary, our GWAS identified novel candidate genes with biological plausibility being promising candidates for replication and further follow-up studies.

Relational stressors as predictors for repeat aggressive and self-harming incidents in child and adolescent psychiatric inpatient settings.

This study examined whether relational stressors such as psychosocial stressors, the therapist's absence and a change of therapist are associated with repeat aggressive or self-harming incidents in child and adolescent psychiatric inpatient care. The study data were derived from critical incident reports and chart reviews of 107 inpatients. In multinomial regression analysis, patients with repeat aggressive or self-harming incidents were compared with patients with single incidents. Results suggested that a higher number of psychosocial stressors and a change of therapist, but not the therapist's absence are predictors for repeat aggressive and self-harming incidents. There was a high prevalence of therapist's absence during both, single and repeat, incidents. Repeat aggressive incidents were common in male children and adolescents with disruptive behavior disorders. Repeat self-harming incidents were common in adolescent females with trauma-related disorders. Patients with repeat aggressive or self-harming incidents had a higher number of abnormal intrafamilial relationships and acute life events than patients with single incidents. Interventions to reduce a change of therapist should in particular target children and adolescents with a higher number of psychosocial stressors and/or a known history of traumatic relational experiences. After a first incident, patients should have a psychosocial assessment to evaluate whether additional relational support is needed.

[Effects of Ward Interventions on Repeated Critical Incidents in Child and Adolescent Psychiatric Inpatient Care]. / Auswirkungen von strukturellen Interventionen auf wiederholte kritische Ereignisse in der stationären Kinder- und Jugendpsychiatrie.

Effects of Ward Interventions on Repeated Critical Incidents in Child and Adolescent Psychiatric Inpatient Care. The aim of this study was to evaluate the effects of several ward interventions (transition to an open ward concept, individualized treatment plans, tiered crisis-management, staff training, quality control) on repeated critical incidents, non-restrictive and restrictive measures. The outcome variables were compared in two time periods, 2007 and 2011. The study included 74 critical incident reports of 51 child and adolescent inpatients that had at least one hospital stay and one critical incident in the selected time periods. Aggressive, self-harming, and absconding incidents were included. The quantitative results suggest that ward interventions can contribute to a reduction of repeated critical incidents and restrictive measures. The qualitative evaluation suggests a cultural change of crisis management.

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.

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.

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.