Childhood trauma is linked to epigenetic age deceleration in young adults with previous youth residential care placements.

Background: Early adversity increases the risk for mental and physical disorders as well as premature death. Epigenetic processes, and altered epigenetic aging in particular, might mediate these effects. While the literature that examined links between early adversity and epigenetic aging is growing, results have been heterogeneous.Objective: In the current work, we explored the link between early adversity and epigenetic aging in a sample of formerly out-of-home placed young adults.Method: A total of N = 117 young adults (32% women, age mean = 26.3 years, SD = 3.6 years) with previous youth residential care placements completed the Childhood Trauma Questionnaire (CTQ) and the Life Events Checklist (LEC-R) and provided blood samples for the analysis of DNA methylation using the Illumina Infinium MethylationEPIC BeadChip Microarray. Epigenetic age was estimated using Hovarth's and Hannum's epigenetic clocks. Furthermore, Hovarth's and Hannum's epigenetic age residuals were calculated as a proxy of epigenetic aging by regressing epigenetic age on chronological age. The statistical analysis plan was preregistered (https://osf.io/b9ev8).Results: Childhood trauma (CTQ) was negatively associated with Hannum's epigenetic age residuals, ß = -.23, p = .004 when controlling for sex, BMI, smoking status and proportional white blood cell type estimates. This association was driven by experiences of physical neglect, ß = -.25, p = .001. Lifetime trauma exposure (LEC-R) was not a significant predictor of epigenetic age residuals.Conclusion: Childhood trauma, and physical neglect in particular, was associated with decelerated epigenetic aging in our sample. More studies focusing on formerly institutionalized at-risk populations are needed to better understand which factors affect stress-related adaptations following traumatic experiences.

Growing literature links early adversity to altered epigenetic aging, yet results have been heterogeneous.We assessed childhood and lifetime trauma exposure using the Childhood Trauma Questionnaire and the Life Events Checklist and estimated epigenetic aging by obtaining Horvath's and Hannum's epigenetic age residuals in a sample of formerly out-of-home placed young adults.In this high-risk sample, childhood trauma, physical neglect in particular, but not lifetime trauma was negatively related to epigenetic aging.

Dealing with the challenges of the pandemic - results of a population-based survey during the second year of the COVID-19 pandemic contrasting benefits and burden.

BACKGROUND: The pandemic and the associated consequences have been ongoing stressors with severe impacts on the population and particularly on families. Research focusing on groups dealing well with the challenges of the pandemic is scarce. Here, we aimed to identify groups being well-adjusted during the pandemic and associated predictors. METHODS: A representative sample of the German population (N = 2,515, 51.6% women, 50.09 years), and a subsample of persons with children or adolescents under the age of 18 (N = 453, 60.3% women, 40.08 years) was assessed from July to October 2021. As huge differences in coping with the pandemic are seen, cluster analysis was performed. RESULTS: Persons in the "well-adjusted cluster" were characterized by higher quality of life, better coping with the pandemic and lower burden of the pandemic. The family subsample well-adjusted cluster was characterized by lower pandemic-associated burden, lower parental stress compared to before the pandemic and a better relationship with the child. Fewer mental health symptoms and less pandemic-associated negative impact on career predicted membership of the well-adjusted cluster in both samples. An interaction between mental health symptoms and the negative impact of COVID-19 on the career was found. CONCLUSIONS: Our results underscore the importance of mental health and work-related factors for coping with the pandemic.

Maternal child maltreatment and trajectories of offspring behavioural and emotional difficulties from age 4 to 7 years - results from a prospective birth cohort study.

Maternal experience of child maltreatment (CM) has been associated with maternal and child mental health. However, evidence about the course of child mental health and maternal CM is scarce. Therefore, this study aims to compare trajectories of mental health in children according to maternal CM exposure and maternal mental health. We included 327 mothers and their singleton child from the Ulm SPATZ Health Study, a prospective birth cohort study. Child mental health was determined by the Strength and Difficulties Questionnaire (SDQ) at the age of 4, 5, 6, and 7 years and maternal CM by the Childhood Trauma Questionnaire (CTQ). Results display that maternal CM is associated with more behavioural and emotional difficulties in children, a trend that tends to increase with older child age. The sum of maternal mental health problems across this time course mediates this association. Male child sex is associated with more mental health problems in the child and the mother. These results provide an important first insight into the relevance of maternal CM on the trajectories of mental health in the offspring and highlight the importance of chronicity and severity of maternal mental health. Further prospective research in cohorts with longer follow-ups up into adolescence and adulthood is needed.

[Structures, aims and needs of early career scientists at the German Center for Mental Health]. / Strukturen, Ziele und Bedürfnisse der Early Career Scientists am Deutschen Zentrum für Psychische Gesundheit.

BACKGROUND: Early career scientists (ECS) are agents of change and driving forces in the promotion of mental health. The German Center for Mental Health (DZPG) is a powerful initiative to guide and support careers in the field of mental health. OBJECTIVE: The DZPG aims to make investments to educate, engage, excite, and empower ECS in an interdisciplinary and interinstitutional scientific community. STRUCTURES, TOPICS AND INITIATIVES: To achieve this, the ECS Board at the DZPG plays a central role and consists of 18 elected ECS representatives. The ECS culture gives members the right of voice and embraces bottom-to-top ideas and acknowledges autonomy and co-determination. The DZPG academy was developed to facilitate communication and networking and encourage collaboration among ECS members. The DZPG also navigates several key issues, such as equality, diversity, inclusion, family friendliness and work-life balance, which are essential for a functioning research landscape. The DZPG also extends opportunities to ECS to develop skills and competencies that are essential for contemporary ECS. It complements nationwide support for ECS with funding opportunities, mental health support at work, careers advice and guidance activities. Importantly, the ECS Board is committed to patient and public involvement and engagement, scientific communication and knowledge transfer to multiple settings. CONCLUSION: The DZPG will contribute to fostering ECS training programs for student and academic exchanges, collaborative research, and pooling of resources to acquire grants and scholarships. It will also support the establishment of hubs for ECS networks and promote the expansion of international competence of ECS in Germany.

Abusive head trauma: The body of the iceberg - A population-based survey on prevalence and perpetrators.

BACKGROUND: Research on abusive head trauma (AHT) is usually research on clinically identified cases, while population-based studies, having the potential to identify cases of shaking that did not end with hospital admission, are missing to date. OBJECTIVE: Thus, we aimed to assess the prevalence of AHT and associated risk factors in a representative sample of the German population. PARTICIPANTS AND SETTING: We conducted a cross-sectional, observational study in Germany from July to October 2021. Using different sampling steps including a random route procedure, a probability sample of the German population was generated. The final sample consisted of 2503 persons (50.2 % female, mean age: 49.5 years). METHODS: Participants were asked about sociodemographic information in a face-to-face interview and whether they had been ever responsible for the care of an infant and whether they had ever performed potential harmful methods including shaking to calm it, intimate partner violence (IPV) and adverse childhood experiences (ACEs) using a questionnaire. RESULTS: In total, 1.4 % of women (N = 18) and 1.1 % of men (N = 13) reported to have at least once shaken an infant to calm it. Ever having used a potential harmful parenting method in calming an infant was reported by 4.9 % of women (N = 61) and 3.1 % (N = 39) of men. No gender differences were seen. A low income, living with someone under 16 in the household and victimization and perpetration of IPV and ACEs are associated with increased risks of shaking and other potential harmful methods to calm an infant. CONCLUSIONS: Our data suggest that despite better knowledge on the dangers of shaking, the percentage of women that shake infants might be higher than previously thought. Also, intimate partner violence and ACEs are key risk factor for shaking and harmful parenting behaviors in general. This has important implications for future prevention programs.

Telemedical Monitoring of Plantar Temperature in Diabetic Patients at Risk of Foot Ulcers.

BACKGROUND: The worldwide prevalence of diabetic foot ulcers (DFUs) among persons with diabetes is estimated at 6.3%, with an annual incidence of 9.1 to 26.1 million persons. The early detection of asymmetrical plantar temperature elevation, followed by reduction of weight-bearing on the affected foot, may be an effective mode of prevention. METHODS: Patients with diabetes and peripheral neuropathy (DFU risk groups 2/3) were monitored for plantar abnormalities with a telemedical system consisting of sole inserts with temperature sensors and photographic documentation. An open, prospective, randomized controlled trial was performed to determine whether this system prevented DFUs. The intervention and control groups were also trained in ulcer prevention and observed in follow-up at 6-month intervals for 24 months. RESULTS: 283 patients were recruited. In 85 137 observation days, DFUs arose in five patients in the control group (n = 143) and in no patient in the intervention group (n = 140). The primary outcome measure was the hazard ratio, which was calculated to be 0.015 (95% confidence interval [0; 19,717]; p = 0.25) after adjustment for age, sex, severity of neuropathy, and risk class. There were 239 alarms and 75 instructions to reduce weight-bearing on the foot. The subjects carried out the telemedical application on about 70% of the days of observation. Quality of life improved in both groups. CONCLUSION: The tele-health system used in this trial is practical and enables the early detection of morbidity. Likely explanations for the unexpectedly low ulceration rate in this trial (and, in turn, for the lack of statistical significance) include the availability of a training program and regular follow-up examinations to patients in both arms of the trial, along with lower mobility levels due to the COVID pandemic.

Adverse childhood experiences increase the risk for low perceived social participation and health-related quality of life in a large-scale population-based study in Germany.

BACKGROUND: Adverse childhood experiences (ACEs) are highly prevalent and increase the risk for long-term adverse health outcomes. Next to well-known ACE-associated risks for morbidity, recent research is increasingly invested in exploring pathways towards health, overall functioning, and partaking in society following early adversity. OBJECTIVES: Thus, this study aims to assess the association between latent classes of ACEs with perceived social participation and health-related Quality of Life (QoL) in a large population-based sample and to explore potential moderators of these associations. METHOD: A representative sample of the German population (N = 2531; Mage = 48.7; 51 % women) was cross-sectionally investigated for ACEs, social participation (KsT-5), and health-related QoL (EuroQol-5D-5L). Latent Class Analysis (LCA) was performed to derive groups with similar ACE patterns. Multiple regression analyses were used to investigate the association of latent classes of ACEs with social participation and health-related QoL and to explore potential moderators. RESULTS: Four distinct latent classes of ACEs were identified; "no/low ACEs" (N = 1968, 77.8 %); "household-dysfunction" (N = 259, 10.2 %), "child abuse and neglect" (N = 188, 7.4 %), and "polyadversity" (N = 116, 4.6 %). Compared to participants in the no/low ACE class, those in the ACE-exposed classes showed overall lower levels of perceived social participation and health-related QoL. The polyadversity class showed lower levels of social participation compared to the two other ACE-exposed classes. Chronic stress, living with a partner, education, current job/educational involvement, and gender were found to moderate these associations in exploratory analyses. CONCLUSIONS: This study shows people exposed to ACEs to have a higher risk for lower perceived social participation and lower health-related QoL - an increased risk, however, is not a deterministic uninventable fortune. Reduction of chronic stress, fostering of social support, and educational and vocational paths as interventional targets are discussed to enable those with precarious starting conditions to partake in society.

Epidemiology of intimate partner violence perpetration and victimisation in a representative sample.

AIMS: Intimate partner violence (IPV) is a major global public health problem. Although IPV is known to be frequent and perpetration and victimisation often co-occur, large representative samples assessing both, male and female IPV perpetration and victimisation and overlaps are missing to date. Thus, we aimed to assess victimisation and perpetration and its overlap in physical, sexual, psychological and economic IPV in a representative sample of the German population. METHODS: We conducted a cross-sectional, observational study in Germany from July to October 2021. Using different sampling steps including a random route procedure, a probability sample of the German population was generated. The final sample consisted of 2503 persons (50.2% female, mean age: 49.5 years). Participants were asked about socio-demographic information in a face-to-face interview and experience of physical, psychological, sexual and economic IPV using a questionnaire. RESULTS: A significant proportion of persons in Germany reporting IPV are both perpetrator and victim for each IPV form. The biggest overlap between perpetration and victimisation was seen for psychological IPV. Major risk factors for IPV perpetration only were male gender and adverse childhood experiences (ACEs) while major risk factors for IPV victimisation only comprised of female gender, low household income and ACEs. In the perpetration and victimisation group, gender differences were less significant; older age and lower household income did increase the likelihood of combined perpetration and victimisation. CONCLUSIONS: We have identified a significant overlap of perpetration and victimisation of IPV in the German population for men and women. However, men are at much higher risk to perpetrate IPV without being a victim. Further research and the development of adapted approaches for contexts of overlapping IPV are necessary.

Retinoid homeostasis in major depressive disorder.

The small, hormone-like molecule retinoic acid (RA) is a vital regulator in several neurobiological processes that are affected in depression. Next to its involvement in dopaminergic signal transduction, neuroinflammation, and neuroendocrine regulation, recent studies highlight the role of RA in homeostatic synaptic plasticity and its link to neuropsychiatric disorders. Furthermore, experimental studies and epidemiological evidence point to the dysregulation of retinoid homeostasis in depression. Based on this evidence, the present study investigated the putative link between retinoid homeostasis and depression in a cohort of 109 patients with major depressive disorder (MDD) and healthy controls. Retinoid homeostasis was defined by several parameters. Serum concentrations of the biologically most active Vitamin A metabolite, all-trans RA (at-RA), and its precursor retinol (ROL) were quantified and the individual in vitro at-RA synthesis and degradation activity was assessed in microsomes of peripheral blood-derived mononuclear cells (PBMC). Additionally, the mRNA expression of enzymes relevant to retinoid signaling, transport, and metabolism were assessed. Patients with MDD had significantly higher ROL serum levels and greater at-RA synthesis activity than healthy controls providing evidence of altered retinoid homeostasis in MDD. Furthermore, MDD-associated alterations in retinoid homeostasis differed between men and women. This study is the first to investigate peripheral retinoid homeostasis in a well-matched cohort of MDD patients and healthy controls, complementing a wealth of preclinical and epidemiological findings that point to a central role of the retinoid system in depression.

Parental stress and physical violence against children during the second year of the COVID-19 pandemic: results of a population-based survey in Germany.

BACKGROUND: Parents and caregivers belonged to those with the highest burdens during the COVID-pandemic. Considering the close link between parental stress and child maltreatment, identifying families with high parental stress is of utmost importance to prevent violence against children. Within this study, we thus aimed to investigate the interplay of parental stress, changes in parental stress, and physical violence against children during the second year of the COVID-pandemic on an exploratory level. METHODS: We conducted a cross-sectional, observational study in Germany from July to October 2021. By using different sampling steps, a representative probability sample of the German population was generated. A subsample of these participants with children under the age of 18 was included for analysis within this study (N = 453, 60.3% females, Mage = 40.08; SD = 8.53). RESULTS: Higher parental stress levels were associated with more physical violence against children, higher levels of own experiences of child maltreatment, and mental health symptoms. An increase in parental stress during the pandemic was associated with female sex, the use of physical violence against children, and parental experience of child maltreatment. Parents who have ever used physical violence against their children have been characterized by higher parental stress levels, a stronger increase in parental stress during the pandemic, own experience of child maltreatment, mental health symptoms and sociodemographic characteristics. Higher parental stress levels, a stronger increase of parental stress during the pandemic, having pre-existing psychiatric disorders, and parental experience of child maltreatment predicted an increased use of physical violence against children during the pandemic. CONCLUSIONS: Our results underscore the importance of parental stress for the risk of physical violence against children, more so in times of overall increased stress due to the pandemic and underline the need for low threshold support for families at risk in times of crises.

The Effects of Climate Change on Mental Health.

BACKGROUND: All over the world, climate change is exerting negative and complex effects on human living conditions and health. In this narrative review, we summarize the current global evidence regarding the effects of climate change on mental health. METHODS: A systematic literature search concerning the direct effects of acute extreme weather events (floods, storms, fires) and chronic stresses (heat, drought) due to climate change, as well as the indirect effects of climate change (food insecurity, migration), on the diagnoses of mental disorders, psychological distress, and psychiatric emergency admissions was carried out in PubMed and PsychInfo, and supplemented by expert selection. 1017 studies were identified, and 128 were included. RESULTS: The heterogeneity of study methods does not permit any overall estimate of effect strength. The available evidence shows that traumatic experiences due to extreme weather events increase the risk of affective and anxiety disorders, especially the risk of post-traumatic stress disorder. Heat significantly increases the morbidity and mortality attributable to mental illness, as well as the frequency of psychiatric emergencies. Persistent stressors such as drought, food insecurity, and migration owing to climate change can also be major risk factors for mental illness. CONCLUSION: The consequences of climate change are stress factors for mental health. Therefore, as global warming progresses, an increasing incidence and prevalence of mental illness is to be expected. Vulnerable groups, such as the (already) mentally ill, children, and adolescents, need to be protected. At the same time, there is a need for further systematic research on the mechanisms of action and effects of climate change on mental function.

Widening epidemiological data on the prevalence of child maltreatment: Validation of the German ICAST-R in a student sample and national household survey.

BACKGROUND: A number of instruments for measuring child maltreatment (CM) prevalence have repeatedly been used across different countries. Although they hold the potential for providing benchmarks to tackle the gap of lacking comparability of CM prevalence across countries, contextual information about the adverse experiences such as perpetrator, chronicity, frequency, or severity are rarely covered. The ISPCAN Child Abuse Screening Tool - Retrospective (ICAST-R) covers these important dimensions. The German version increases the number of available versions to 21 different languages. Spoken by about 120 million people, German is one of the 20 most prevalent languages around the world. Moreover, the ICAST-R is intended to be used with young adults. This study further aims at adding towards the gap of psychometrics in older age groups. METHODS: Analyses are based on both a sample of German students (n = 333) and a nationally representative household survey (n = 2515). The validation process covered six steps: (1) Analyses of missing data on single items, (2) calculation of descriptive statistics to estimate the prevalence CM as well as subjective severity and main perpetrators. (3) Structural validity of the four conceptualized subtypes of CM (neglect, physical abuse, emotional abuse and sexual abuse) was tested using confirmatory factor analyses (CFA). Next (4), equivalence testing by multigroup confirmatory factor analyses (MGCFA) on age groups was conducted within the representative sample; (5) reliability was tested by determining internal consistencies for each subscale via the McDonald's Omega, Kuder-Richardson 20 (KR-20), and Cronbach's alpha. Lastly (6), criterion validity was tested in regression models comparing depressive/anxious symptomatology for single victimization and polyvictimization. RESULTS: The German ICAST-R yielded low missing values items in both samples. 16 % of the participants in the national household survey reported neglect, 20.3 % physical abuse, 22.2 % emotional abuse, and 8.6 % sexual abuse. Polyvictimization was prevalent with 20.6 % of subjects reporting >2 types of CM. Students in the pilot-survey reported much higher prevalence estimates than participants in the nationally representative sample. The types of CM subjectively rated as most harmful were emotional abuse and sexual abuse. In both samples, structural validity was similarly confirmed as CFA was reproducing the four conceptualized subtypes of CM with adequate fit (household survey: CFI 0.919, TLI 0.907, RMSEA 0.017, SRMR 0.046). Internal consistency achieved acceptable and comparable values for all three types of coefficients; criterion validity was established with a significant dose-response effect of CM experiences on both anxiety and depressive symptoms/diagnoses. Age dependent analyses on structural validity (MGCFA) and reliability in the household survey revealed potential weaknesses of items. CONCLUSION: The German version of the ICAST-R both widens the possibility of international CM prevalence comparison and provides novel epidemiological data for Germany on subjective severity of CM and CM perpetrators. Even in the presence of a marked selection bias, the ICAST-R had similarly good psychometric properties in the student and nationally representative household sample. Except for issues with two items, equivalence testing was comparable across age groups.

Survey on Reporting of Child Abuse by Pediatricians: Intrapersonal Inconsistencies Influence Reporting Behavior More than Legislation.

Background: Internationally, various laws govern reporting of child abuse to child protection services by medical professionals. Whether mandatory reporting laws are in place or not, medical professionals need internal thresholds for suspicion of abuse to even consider a report ("reasonable suspicion" in US law, "gewichtige Anhaltspunkte" in German law). Objective: To compare internal thresholds for suspicion of abuse among US and German pediatricians, i.e., from two countries with and without mandatory reporting laws. Participants and Setting: In Germany, 1581 pediatricians participated in a nationwide survey among child health professionals. In the US, a survey was mailed to all Pennsylvania pediatricians, and 1249 participated. Methods: Both samples were asked how high in their rank order of differential diagnoses child abuse would have to be when confronted with a child's injuries to qualify for reasonable suspicion/gewichtige Anhaltspunkte (differential diagnosis scale, DDS). In a second step, both had to mark a 10-point likelihood scale (0-100%) corresponding to reasonable suspicion/gewichtige Anhaltspunkte (estimated probability scale, EPS). Results: While for almost two-thirds of German pediatricians (62.4%), child abuse had to be among the top three differential diagnoses for gewichtige Anhaltspunkte, over half of the US respondents (48.1%) had a lower threshold for reasonable suspicion. On the estimated probability scale, over 65% in both samples indicated that the probability of abuse had to exceed 50% for reasonable suspicion/gewichtige Anhaltspunkte. There was great variability between the two countries. Conclusions: There are similar uncertainties in assessing cases of suspected child abuse in different legal systems. There is a need for debates on thresholds among medical professionals in both countries.

Adverse and traumatic exposures, posttraumatic stress disorder, telomere length, and hair cortisol - Exploring associations in a high-risk sample of young adult residential care leavers.

Background: Childhood adversities (CAs), potentially traumatic exposures (PTEs), and posttraumatic stress disorder (PTSD) are known to increase the risk for poor health outcomes, including diseases of aging and early mortality. Telomere length (TL) and hair cortisol concentrations (HCC) are biomarkers known to be associated with CA and PTEs, and PTSD, but there is considerable heterogeneity in findings. Objectives: This study aims to investigate the association of CAs, PTEs, and PTSD with TL and HCC in a high-risk sample of young adults who were previously placed in youth residential care institutions throughout Switzerland. Method: Our sample includes 130 participants (30.8% women, M Age = 26.5 ± 3.7 years) with previous youth residential care placements (MPlacements= 3.9). CAs and PTEs, as well as PTSD, were assessed with self-reported questionnaires and semi-structured clinical interviews. Immune cell TL was measured with quantitative polymerase chain reaction (qPCR) in whole blood. Hair samples were collected for HCC measurement and assayed with high-sensitivity ELISA. Multivariate regression models were fitted to describe the associations between CAs, PTEs, and PTSD with TL and HCC, adjusting for covariates. Results: In our high-risk sample, a higher burden of CAs, PTEs, Criterion A trauma, and PTSD was associated with longer TL. PTEs, Criterion A trauma, and PTSD were associated with lower HCC, however no significant associations between CAs and HCC were found. The magnitude of these effects varied depending on the dimensional or categorical nature of the stress-phenotype and the specific measure used. Conclusions: Our findings are in contrast with many, but not all, previous studies of associations between adversity and both TL and HCC. For instance, our findings are in line with other studies that find a state of hypocortisolism in PTSD. Better measurement of adversities and trauma, multisystem biomarker approaches, and more research in larger high-risk samples at the upper end of the adversity-continuum is warranted.

Adverse childhood experiences growing up in East or West Germany or abroad.

Background: Adverse childhood experiences (ACEs) are potentially traumatic events that occur before the age of 18. The term encompasses various adverse childhood experiences, e.g., physical, psychological, and sexual abuse, physical and psychological neglect, and family dysfunction. Prevalence estimates for a broad spectrum of ACEs against the background of where childhood and adolescence were spent are scarcely available in Germany. This study examines the frequencies of adverse childhood experiences, considering growing up in East or West Germany or abroad and interacting with different age cohorts and gender. Methods: A total of 5,018 individuals (51.4% female) aged 14 years and older were retrospectively assessed on adverse childhood experiences using questionnaires "adverse childhood experiences" (ACE). Logistic regression models were used to analyze the association between birth cohort, gender, and where a person grew up. Descriptive statistics and univariate analyses were used to calculate frequencies, proportions, and unadjusted associations for each variable. Results: 37.4% (N = 1,878) of respondents reported experiencing at least one form of ACE. Individuals who grew up abroad report significantly more adverse childhood experiences than individuals in East or West Germany. Men and women who grew up in East Germany reported a lower rate of ACEs. We found significant effects for all predictors: Where childhood and adolescence were predominantly spent, year of birth, and gender. Significant differences in the prevalence of adverse childhood experiences within the gender groups were only found for sexual and physical abuse and substance dependence in the household. Conclusion: The results suggest that the socio-political context plays an essential role in the experience of adverse childhood experiences, both in frequency and risk. Thus, child abuse and neglect studies should increasingly focus on societal risk and protection mechanisms.

Effect of Minocycline on Depressive Symptoms in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial.

Importance: Insufficient treatment response and resulting chronicity constitute a major problem in depressive disorders. Remission rates range as low as 15% to 40% and treatment-resistant depression (TRD) is associated with low-grade inflammation, suggesting anti-inflammatory interventions as a rational treatment strategy. Minocycline, which inhibits microglial activation, represents a promising repurposing candidate in the treatment of TRD. Objective: To determine whether 6 weeks of minocycline as add-on to antidepressant treatment as usual can significantly reduce depressive symptoms in patients with TRD. Design, Setting, and Participants: The study was conducted in Germany and designed as a multicenter double-blind randomized clinical trial (RCT) of 200 mg/d minocycline treatment over a course of 6 weeks with a 6-month follow-up. Participants were recruited from January 2016 to August 2020 at 9 university hospitals that served as study sites. Key inclusion criteria were a diagnosis of major depressive disorder (according to Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] criteria), severity of depressive symptoms on the Hamilton Depression Rating Scale (HAMD-17) greater than or equal to 16 points, aged 18 to 75 years, body mass index 18 to 40, Clinical Global Impression Scale (CGI-S) greater than or equal to 4, failure to adequately respond to an initial antidepressant standard medication as per Massachusetts General Hospital Antidepressant Treatment History Questionnaire, and stable medication for at least 2 weeks. A total of 258 patients were screened, of whom 173 were randomized and 168 were included into the intention-to-treat population. Statistical analysis was performed from April to November 2020. Interventions: Participants were randomized (1:1) to receive adjunct minocycline (200 mg/d) or placebo for 6 weeks. Main Outcomes and Measures: Primary outcome measure was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 6 analyzed by intention-to-treat mixed model repeated measures. Secondary outcome measures were response, remission, and various other clinical rating scales. Results: Of 173 eligible and randomized participants (84 randomized to minocycline and 89 randomized to placebo), 168 formed the intention-to-treat sample (79 [47.0%] were women, 89 [53.0%] were men, 159 [94.6%] were White, 9 [6.4%] were of other race and ethnicity, including Asian and unknown ethnicity), with 81 in the minocycline group and 87 in the placebo group. The mean (SD) age was 46.1 (13.1) years, and the mean (SD) MADRS score at baseline was 26.5 (5.0). There was no difference in rates of completion between the minocycline (83.3% [70 of 81]) and the placebo group (83.1% [74 of 87]). Minocycline treatment did not alter the course of depression severity compared with placebo as assessed by a decrease in MADRS scores over 6 weeks of treatment (1.46 [-1.04 to 3.96], P = .25). Minocycline treatment also exhibited no statistically significant effect on secondary outcomes. Conclusions and Relevance: In this large randomized clinical trial with minocycline at a dose of 200 mg/d added to antidepressant treatment as usual for 6 weeks, minocycline was well tolerated but not superior to placebo in reducing depressive symptoms in patients with TRD. The results of this RCT emphasize the unmet need for therapeutic approaches and predictive biomarkers in TRD. Trial Registration: EU Clinical Trials Register Number: EudraCT 2015-001456-29.

Changes in authoritarianism before and during the COVID-19 pandemic: Comparisons of latent means across East and West Germany, gender, age, and education.

Modern theories of authoritarianism have stressed the importance of threat to the expression of authoritarian attitudes and intolerance. Arguably, authoritarian tendencies may have increased during COVID-19 pandemic, a major threat to life and security. One issue arising when comparing mean scores is that of measurement invariance. Meaningful comparisons are only possible, if latent constructs are similar between groups and/or across time. This prerequisite is rarely ever tested in research on authoritarianism. In this study, we aim to analyze the short scale for authoritarianism KSA-3 by investigating its measurement invariance on two levels (three first-order and one second-order factors) and latent mean changes using two German representative samples (N = 4,905). Specifically, we look at differences before and during the pandemic (2017 vs. 2020). While measurement invariance holds across both levels in all conditions, we find a decrease in latent means in 2020, contrary to expectations and established theories. Moreover, latent means differ with regard to gender, education, and east-west Germany. We conclude that analyses of latent means and measurement invariance instead of mean comparisons with composites should become the standard. Future studies should focus on threat as a moderator between authoritarianism and intolerance, and on possible interactions with context variables.

Adverse childhood experiences are associated with a higher risk for increased depressive symptoms during Covid-19 pandemic - a cross-sectional study in Germany.

BACKGROUND: Covid-19 pandemic has been profoundly affecting people around the world. While contact restrictions, school closures and economic shutdown were effective to reduce infection rates, these measures go along with high stress for many individuals. Persons who have experienced adverse childhood experiences (ACEs) have an increased risk for mental health problems already under normal conditions. As ACEs can be associated with a higher vulnerability to stress we aimed to assess the role of ACEs on depressive symptoms during the Covid-19 pandemic. METHODS: In a cross-sectional online survey, 1399 participants above the age of 18 years were included during the first lockdown in Germany. Via two-way repeated measures ANOVA, differences in depressive symptoms before (retrospectively assessed) and during the pandemic were analyzed. Linear regression analyses were performed in order to identify predictors for increase of depressive symptoms. RESULTS: Compared to prior to the Covid-19 pandemic, depressive symptoms increased among all participants. Participants with ACEs and income loss reported about a stronger increase of depressive symptoms. Other predictors for increased depressive symptoms were young age and a lack of social support. CONCLUSIONS: Based on these results, ACEs are a significant predictor for an increase in depressive symptoms during the pandemic, indicating that personss with ACEs may be a risk group for mental health problems during the current and potential later pandemics. These findings underline the relevance of support for persons who have experienced ACEs and may help to provide more targeted support in possible scenarios due to the current or possible other pandemics. Besides, economic stability seems to be of prior importance for mental health.

The Impact of Mental Health and Sociodemographic Characteristics on Quality of Life and Life Satisfaction during the Second Year of the COVID-19 Pandemic-Results of a Population-Based Survey in Germany.

A decreased quality of life was shown for numerous factors at the beginning of the pandemic. However, it is important to identify people who are at-risk for long-term impairments during the pandemic and its aftermath. Within this study, we aimed to investigate quality of life within a German population-based sample (2515 participants; 51.6% female; mean age 50.09 years) during the second year of the pandemic (2021). Our results showed that the majority reported no pandemic-associated change in quality of life at this state of the pandemic. Higher life satisfaction was associated with fewer mental health problems, no pre-existing somatic and psychiatric disorders, higher income, no income loss during the pandemic, living with others, and younger age. In contrast, in a high-risk group encompassing participants with lower quality of life, only mental health, pre-existing somatic disorders, and living alone had significant associations with quality of life, indicating a smaller scope for improvement in this high-risk group. Age, income loss, and depressive symptoms predicted a decrease in quality of life since the beginning of the pandemic. Our results highlight the importance of mental health, especially in times of pandemic, and underline the need for low-threshold mental health support.