BACKGROUND:Childhood maltreatment (CM), encompassing abuse and neglect, is highly prevalent and associated with elevated risk for major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and other related conditions. However, the extent to which neuroanatomical alterations in MDD and PTSD are attributable to CM is uncertain. METHODS:Here, we analyzed CM and whole-brain magnetic resonance imaging (MRI) data from 3711 participants in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) MDD and PTSD Working Groups (25 sites; mean age = 33.3 ± 13.0 years; 59.9% female). Normative modeling estimated deviation z scores for 14 subcortical volume, 68 cortical thickness (CT), and 68 surface area (SA) measures. To identify transdiagnostic effects, associations between CM and brain deviation scores were evaluated across all participants (patients and healthy control participants) stratified by sex and 3 age bins (pediatric, young adult, older adult). RESULTS:In young adults (ages 18-35), abuse was associated with larger volumes in the thalamus and pallidum, thinner isthmus cingulate and middle frontal regions, and thicker medial orbitofrontal cortex; there were no significant effects in pediatric (≤18 years) participants. The strongest effects were observed in young female adults (|β| = 0.07-0.22, q < .05): Greater abuse and neglect were correlated with smaller hippocampus and putamen volumes, thinner entorhinal cortex, and smaller SA in fusiform/inferior parietal regions and with larger SA in the orbitofrontal and occipital cortices. In males, abuse had widespread effects on CT and SA (|β| = 0.1-0.18, q < .05); effects for neglect were minimal. CONCLUSIONS:Our findings of age- and sex-specific instantiations of CM on brain morphometry highlight the importance of developmental context in understanding how adverse experiences shape neurobiological vulnerability to MDD and PTSD.

Background: Around 60% of patients with major depressive disorder (MDD) report adverse childhood circumstances. Such adversities have been shown to be an important factor in the development and maintenance of depression. For this reason, specific therapies would be required to treat patients with MDD and emotional childhood adversities. We aimed to investigate the clinical outcomes of ego state therapy (EST) compared with eye movement desensitisation and reprocessing (EMDR), a therapy already established for MDD. Methods: In the single-blind, randomised, active controlled, feasibility trial, patients with MDD, aged 18-75 years, were allocated 1:1 to trauma-focused therapies EMDR or EST. Participants underwent 14 sessions of psychotherapy. The primary outcome was the change in depression severity assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary clinical outcomes included response, remission from depression, posttraumatic stress disorder (PTSD) symptoms, emotion regulation and aggression. Findings: 40 participants were included. Both EMDR and EST significantly decreased depression symptom scores with a large effect size (F (2/114) = 9·908, p=0·0001, Cohen’s f = 0·417). No significant difference between treatment groups (F (1/114) = 0·407, p = 0·525) and no significant interactive effect between visits and treatment groups (F (2/114) = 0·08, p = 0·924) were detected. Secondary outcomes BDI-II scores and PTSD symptoms also significantly decreased over time. There was no significant effects on aggression scores, self-regulation, and adaptive and maladaptive cognitive and emotional regulation. No adverse events of special interest were reported. Interpretation: EST was not inferior to the well-established EMDR, supporting its potential in MDD with childhood adversity. Both therapy programmes not only show effects on depressive symptoms, but also on PTSD symptoms. The trial provides important information about the feasibility including efficacy and the sample size required for a confirmatory regulatory trial.

Introduction:Children of mentally ill parents have an increased risk of developing a mental illness. From an ethical and health-economic perspective, psychotherapeutic care for this risk group is necessary to counter the risk of transgenerational transmission of mental illness. The psychosocial situation of affected families is complex and requires customized support. Within the Children-of-Mentally-Ill-Parents-Network (CHIMPS-NET), three family-based, needs-tailored new forms of care (NFC) - based on the manualized CHIMPS intervention - are implemented and evaluated at 21 locations in Germany. The online intervention iCHIMPS is described in a separate study protocol. Methods:For each NFC, a prospective, rater-blinded, cluster-randomized, controlled study is conducted. Data is collected from the perspective of both parents, all children aged 8 years and older, external raters and therapists at four measurement points: at baseline (T1) and 6 (T2), 12 (T3) and 18 (T4) months after randomization. Allocation to the respective trials is based on baseline assessments of children's mental health symptoms/diagnoses and family functionality, which is followed by randomization. We hypothesize that children in the intervention groups (IGs) have fewer parent-reported mental health problems at T3 than in the respective control groups (CGs), which receive Treatment-as-Usual (TAU). The biometric effect evaluation is supplemented by health economic evaluations and a qualitative evaluation. Discussion:CHIMPS-NET has both raised awareness for children of mentally ill parents and enabled various stakeholders to network with each other. The network contributes to evidence-based care for this risk group. An update of the CHIMPS manual regarding the customized NFC is in process. Clinical trial registration:https://www.bfarm.de/DE/Das-BfArM/Aufgaben/Deutsches-Register-Klinischer-Studien/_node.html; DRKS00020380; https://www.clinicaltrials.gov: NCT04369625.

Background and Hypothesis Both elevated inflammatory markers and aberrant functional connectivity have been detected in patients with schizophrenia, but there is limited knowledge on the relationship between the two phenomena. Some positive symptoms may arise from external misattribution of self-generated actions mediated by decoupling of the default mode network (DMN) with sensory processing regions. Since the anterior DMN also exhibits bidirectional interaction with the immune system, we hypothesized its decoupling would be associated with elevated inflammatory markers as well as the burden of positive symptomatology. Study Design Resting-state functional magnetic resonance imaging, diffusion tensor imaging (DTI), clinical and laboratory data (serum concentrations of interleukin-6 and C-reactive protein) were collected within a neuroimaging trial on schizophrenia. Neuroimaging data were assessed applying seed-to-voxel and region-of-interest-to-region-of-interest functional connectivity analyses as well as DTI tractography. Associations between neuroimaging and laboratory as well as behavioral data were studied employing regression analyses. Study Results For both inflammatory markers, a consistent pattern of hypo-connectivity emerged between the anterior DMN and different brain regions involved in sensory processing and self-monitoring. The strongest association was detected for the connectivity between the anterior DMN and the right parietal operculum which was not explained by the structural integrity of the respective white matter tract. Finally, this functional connection was correlated both with the burden of positive and negative symptoms. Conclusions Our findings reveal a mechanistically plausible neurobiological link between inflammation and psychopathology in schizophrenia.

BACKGROUND:Patients with Major Depressive Disorder (MDD) exhibit biased information processing. This study investigates the clinical and neural efficacy of a cognitive bias modification (CBM) training in patients and healthy control (HCS), fostering processing of positive emotion stimuli. METHODS:In a single-blind randomised controlled trial (DRKS00029756), MDD outpatients and HCS, aged 18-60 years, were randomised to positivity training (PT) or control training (CT). Randomisation was carried out by study assistants, blinding researchers. Participants underwent 10 tablet-based dot-probe sessions over 14 days. PT implicitly redirected attention toward positive stimuli to improve depressive symptoms. Primary outcome was pre and post-training EEG-derived Early Posterior Negativity (EPN), investigating neural sensitivity towards positive stimuli. Secondary clinical outcomes included changes in depression symptoms. FINDINGS:From February 2023 to October 2024, 240 participants were included (119 MDD; 121 HCS). 62 MDD and 61 HCS underwent PT; 57 MDD and 60 HCS received CT. In MDD, EPN to positive high arousal stimuli revealed an interaction between time (pre/post) and training (PT/CT), F(1,97) = 5.017, p < 0.028, η2 = 0.049. The between-treatment difference was 1.65 μV, 95% CI [0.19, 3.11]. EPN amplitudes shifted towards negativity in PT and positivity in CT. Depression symptom decreased from pre to post and from pre to follow-up. With respect to adverse events, one patient in the control training was regularly admitted to hospital. INTERPRETATION:CBM positivity training was associated with neural changes in MDD, supporting its potential to target pre-attentive positive emotion processing. Further EEG follow-up and higher stimulus contrasts in the training conditions may clarify clinical relevance. FUNDING:Funded by DFG (ID: 507720021).

Research has focused on identifying neurobiological risk factors associated with aggressive behavior in order to improve prevention and treatment efforts. This study aimed to characterize microstructural differences in white matter (WM) integrity in individuals prone to aggression. We hypothesized that altered cerebral WM microstructure may underlie normal individual variability in aggression and tested this using a case-control design in healthy individuals. Diffusion tensor imaging (DTI) was used to examine WM changes in martial artists (n = 29) and age-matched controls (n = 31). We performed tract-based spatial statistics (TBSS) to identify differences in axial diffusivity (AD), fractional anisotropy (FA) and mean diffusivity (MD) between the two groups at the whole-brain level. Martial artists were significantly more aggressive than controls, with increased MD in parietal and occipital areas and increased AD in widespread fiber tracts in the frontal, parietal and temporal areas. Positive associations between AD/MD and (physical) appetitive aggression were identified in several clusters, including the corpus callosum, the superior longitudinal fasciculus and the corona radiata. Our study found evidence for WM microstructural changes associated with aggressiveness in a community case-control sample. Longitudinal studies with larger cohorts, taking into account the dimensional nature of aggressiveness, are needed to better understand the underlying neurobiology.

Introduction:Nitrous oxide (N2O) is used for anesthetic purposes but has gained popularity as a recreational substance. Despite its potentially severe adverse effects, knowledge about N2O use within psychiatric populations is limited. This study aimed to evaluate the life-time prevalence and patterns of N2O consumption among patients with psychiatric disorders. Methods:A retrospective observational cohort study was conducted at the Department of Psychiatry, Psychotherapy and Psychosomatics of the Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Hospital, involving assessments of N2O use lifetime prevalence among patients in various psychiatric settings over a six-month period in 2024. Further data on demographic characteristics and psychiatric diagnoses were collected from electronic patient records. Results:Out of 287 screened records, 22 patients (7.67%) reported a N2O use history, with a positive statistical relationship between younger age and positive lifetime prevalence (mean age: 28.14 ± 7.29 years, range 19-48 years, 6/22 female). Most users acquired N2O through low-threshold means such as friends or social events. The predominant psychiatric diagnoses among users included major depressive disorder, cannabis-related disorder and attention deficit and hyperactivity disorder. Discussion:This study highlights the concerning life-time prevalence of N2O use in a clinical psychiatric sample, emphasizing the need for increased awareness and education regarding its potential risks and side effects. Given the vulnerability of this population to substance-related issues, routine assessment for N2O use should be integrated into standard psychiatric evaluations.

We investigated whether the brain age gap (BAG)—the difference between chronological age and age estimated from structural MRI scans—is associated with long-term disease course in affective disorders, using a prospective nine-year follow-up design. T1-weighted MRI data were collected at two time points (mean interval = 8.98 ± 2.20 years) from patients with Major Depressive Disorder (MDD; N = 32), Bipolar Disorder (BD; N = 6), and healthy controls (HC; N = 37) across two sites. Using a brain age prediction model trained on a sample of over 10,000 subjects of the German National Cohort (GNC), we estimated individual BAG at baseline and follow-up using gray matter segments derived from MRI images. Employing linear-mixed-effects models, we tested main effects of diagnosis and hospitalizations as well as their interaction with time on BAG. In an exploratory analysis, we tested if BAG at baseline was predictive of hospitalizations during the nine-year follow-up using logistic regression and 10-fold nested cross-validation. MDD patients showed significantly higher BAG compared to HC (2.27 ± 5.68 vs. 1.00 ± 5.12 years, d = –0.23), while BAG in BD patients was descriptively elevated (4.71 ± 5.40 years). In the Münster subsample (N = 52), patients with at least one hospitalization had higher BAG than those without (4.16 ± 5.74 vs. 1.65 ± 5.41 years, d = –0.45). No group-by-time interaction was observed. Higher BAG at baseline predicted hospitalization during follow-up (p = 0.035), although cross-validated prediction accuracy (64.3%) did not reach significance (p = 0.071). BAG remained stable over time and was not influenced by future recurrence, supporting its role as a potential trait-like marker of vulnerability to illness recurrence. While exploratory, these findings suggest that BAG may capture individual risk for future hospitalization in affective disorders.

Background Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an effective non-pharmacological, non-invasive intervention for depression. However, the optimal strategy for localising the DLPFC treatment site on the patient’s scalp is heavily disputed. Routine strategies were previously incrementally refined and compared in terms of anatomical accuracy, but little is known about their impact on clinical outcomes.Objective To assess the impact of three common scalp-based heuristics for magnetic coil positioning on the treatment outcome of rTMS.Methods This retrospective analysis of real-world clinical data involved patients suffering from a major depressive episode (n=94) who received a 4-week course of excitatory rTMS to the left DLPFC. The treatment target (ie, coil position) was either determined at an absolute distance anterior to the motor hotspot (‘6 cm rule’) or defined in reference to the EEG electrode position F3 using a traditional (‘Beam F3’) or optimised (‘Beam F3 Adjusted’) approach.Findings There was no statistically significant difference between the ‘6 cm rule’ and the ‘Beam F3’ method nor between the ‘Beam F3’ and the ‘Beam F3 Adjusted’ method in head-to-head comparisons of averaged per cent change of scores on depression rating scales (all p>0.605) and response rate (all p>0.475).Conclusions Enhancing targeting precision via scalp-based heuristics does not affect treatment outcomes.Clinical implications There is no need for clinicians to switch from their familiar to an ‘advanced’ approach among these common targeting heuristics.

This study aims to understand how secondary use of health records can be done for prediction, detection, treatment recommendations, and related tasks in clinical decision support systems. Articles mentioning the secondary use of EHRs for clinical utility, specifically in prediction, detection, treatment recommendations, and related tasks in decision support were reviewed. We extracted study details, methods, tools, technologies, utility, and performance. We found that secondary uses of EHRs are primarily retrospective, mostly conducted using records from hospital EHRs, EHR data networks, and warehouses. EHRs vary in type and quality, making it critical to ensure their completeness and quality for clinical utility. Widely used methods include machine learning, statistics, simulation, and analytics. Secondary use of health records can be applied in any area of medicine. The selection of data, cohorts, tools, technology, and methods depends on the specific clinical utility. The process for secondary use of health records should include three key steps: 1. Validation of the quality of EHRs, 2. Use of methods, tools, and technologies with proactive training, and 3. Multidimensional assessment of the results and their usefulness. : PROSPERO registration number CRD42023409582

BACKGROUND:Altered emotion processing, accompanied by cognitive bias leading to reduced positive reactivity and increased sensitivity to negative experiences, are core symptoms of Major Depressive Disorder (MDD), but the biological underpinnings are not yet resolved. Aim of the present study was to examine event-related P100 correlates of altered emotion processing in MDD compared to healthy control subjects (HCS). METHOD:Here, we assessed 87 MDD patients (age: 36.25 ± 13.38 years, 36 males, 51 females) and 100 HCS (age: 33.23 ± 11.63 years, 31 males, 69 females) using a 64-channel EEG system. P100 was regarded to amplitudes and latencies at left (P7/P5/P3/P07/P03/O1) and right (P8/P6/P4/PO8/PO4/O2) hemisphere electrodes in response to emotional stimuli differing in valence (positive/negative), arousal (low/high) and neutral target status (target/non-target). RESULTS:HCS exhibited greater P100 amplitudes over the right hemisphere, whereas participants with MDD showed no hemispheric asymmetry. Amplitudes were higher in women than in men and in individuals with higher state anxiety scores. Unmedicated participants had higher amplitudes than those taking SSRIs or SNRIs, whereas combination therapy showed the highest amplitudes overall. SSRI use was associated with the shortest P100 latencies, while SNRIs were linked to the longest latencies. CONCLUSION:No valence or arousal effects were observed. The data indicate right-hemispheric dominance in early visual processing among HCS, which was reduced in MDD subjects, suggesting diminished hemispheric lateralization in this group. Gender, anxiety level, and medication status significantly influenced P100 amplitude and latency, highlighting subtle alterations in early visual processing patterns in MDD.

BACKGROUND:Externalizing and internalizing disorders are common in youth but are often studied separately, preventing researchers from identifying shared (i.e., transdiagnostic) alterations in brain structure. Using data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium, we conducted a mega-analysis to identify shared and distinct cortical and subcortical brain alterations across internalizing (anxiety disorders and depression) and externalizing (attention-deficit/hyperactivity disorder [ADHD] and conduct disorder [CD]) disorders in youth. METHODS:3D T1-weighted magnetic resonance imaging data from youths (age range 4-21 years) with anxiety disorders (n = 1044), depression (n = 504), ADHD (n = 1317), and CD (n = 1172) along with healthy control participants (n = 4743) were analyzed. We assessed group differences in regional cortical thickness, surface area (SA), and subcortical volume using linear models, adjusted for site, age, and sex, as well as total intracranial volume in the SA and subcortical volume models. RESULTS:We observed transdiagnostic associations, with both internalizing and externalizing disorders characterized by lower SA in the insula, entorhinal cortex, and middle temporal gyrus and lower amygdala volume (Cohen's ds = -0.07 to -0.24) as well as total SA and intracranial volume (ds = -0.11 to -0.25). Externalizing-specific reductions in SA were observed in frontoparietal regions (ds = -0.08 to -0.13), but no internalizing-specific associations were identified. Disorder-specific alterations were identified for ADHD, CD, and anxiety disorders but not depression. CONCLUSIONS:Both common and disorder-specific alterations were identified, with regions involved in salience attribution and emotion processing implicated across internalizing and externalizing disorders. These novel findings can guide future research targeting common biological processes across youth psychiatric disorders as well as features unique to individual disorders.

Background: We investigated associations of the brain age gap (BAG), the difference between actual and estimated age derived from MRI scans, with disease course over nine years in patients with affective disorders in a long-term prospective design. Methods: At two time-points, we acquired T1-weighted MRI images (mean [SD] follow-up period 8.98 [2.20] years) of patients with Major Depressive Disorder (MDD; N=32) and Bipolar Disorder BD; N=6) and healthy controls (HC; N = 37) at two sites (Dublin, Muenster). Using a brain age prediction model trained on a sample of over 10,000 subjects of the German National Cohort (GNC), we estimated individual BAG at two time-points (baseline and follow-up) using gray matter segments derived from MRI images. Employing linear-mixed-effects models, we tested main effects of diagnosis and hospitalizations during follow-up on BAG at baseline and follow-up, as well as their interaction with time respectively. In an exploratory analysis, we tested if BAG at baseline was predictive of hospitalizations during the nine-year follow-up using logistic regression and 10-fold nested cross-validation. Results: MDD patients showed a larger BAG compared to HC (MDD>HC: p=.039, MDD vs. BD: n.s.), while BD patients only showed a tendency for a larger BAG (p = .066). In the Muenster subsample (N=52), patients with hospitalizations showed a higher BAG compared to patients without hospitalizations (p=.001). No significant group-by-time interaction could be detected. However, higher BAG at baseline was associated with the number of hospitalizations during follow- up (p=.018), however, the cross-validation of our prediction with an accuracy of 64.3% was not significant (p=.071). Discussion: Our results show that BAG did not change over time as a function of patients' course of disease. The present study rather suggests that a higher estimation of biological aging (higher BAG) predicts future hospitalizations. Therefore, BAG may indicate a patient's vulnerability to future recurrence. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to UD; SFB-TRR58, Projects C09 and Z02 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Muenster (grant Dan3/012/17 to UD), and the Else Kroener-Fresenius-Stiftung (grant 2022_EKEA.102 to KF) as well as the Graduate Academy of the TU Dresden with funds of the Federal Ministry of Education and Research (BMBF) and the Freestate of Saxony under the Excellence Strategy of the Federal Government and the Laender (to KF). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The institutional review boards of the medical faculty of the University of Muenster and the Trinity College Dublin gave ethical approval for this work. All participants gave written informed consent according to the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All raw MRI data in the present study are available upon reasonable request to the authors. All processed data and scripts are available online at https://osf.io/qadxz/.

BACKGROUND:The definition of long-term courses of depression is heterogeneous. Chronic and treatment-resistant courses, in particular, represent a high-cost factor and greatly reduce the quality of life. Based on the pharmacotherapeutic treatment-resistant depression (TRD), more and more systemic approaches are becoming important. OBJECTIVE:This narrative review provides an overview of the long-term course of depressive disorders, including various definitions and influencing factors. In addition, an overview of biomarker research on treatment response with a focus on neuroimaging is presented. MATERIAL AND METHODS:A selective literature search was conducted in PubMed and Google Scholar for a narrative review. Particular attention was given to larger cohort studies, systematic reviews, meta-analyses and studies on the prediction of treatment response. RESULTS:Chronic and treatment-resistant courses mean a relevant reduction in the quality of life and increased health risks. The assessment of treatment response is a definitional challenge: An alternative to TRD is the systemically oriented difficult to treat depression (DTD). The focus is thus moving away from symptom reduction towards controlling the level of functioning. Biomarker research for treatment response offers potential but currently mainly serves to gain theoretical knowledge. CONCLUSION:Recording the long-term course of depressive illnesses is important, but also complex. Clinical interventions should therefore include a continuous monitoring and the focus on maintaining the quality of life.

The brain's default mode network (DMN) and the executive control network (ECN) switch engagement are influenced by the ventral attention network (VAN). Alterations in resting-state functional connectivity (RSFC) within this so-called triple network have been demonstrated in patients with major depressive disorder (MDD) or anxiety disorders (ADs). This study investigated alterations in the RSFC in patients with comorbid MDD and ADs to better understand the pathophysiology of this prevalent group of patients. Sixty-eight participants (52.9% male, mean age 35.3 years), consisting of 25 patients with comorbid MDD and ADs (MDD + AD), 20 patients with MDD only (MDD) and 23 healthy controls (HCs) were investigated clinically and with 3T resting-state fMRI. RSFC utilizing a seed-based approach within the three networks belonging to the triple network was compared between the groups. Compared with HC, MDD + AD showed significantly reduced RSFC between the ECN and the VAN, the DMN and the VAN and within the ECN. No differences could be found for the MDD group compared with both other groups. Furthermore, symptom severity and medication status did not affect RSFC values. The results of this study show a distinct set of alterations of RSFC for patients with comorbid MDD and AD compared with HCs. This set of dysfunctions might be related to less adequate switching between the DMN and the ECN as well as poorer functioning of the ECN. This might contribute to additional difficulties in engaging and utilizing consciously controlled emotional regulation strategies.

The Electronic Health Record system BUPdata served Norwegian Child and Adolescent Mental Health Services (CAMHS) for over 35 years and is still an important source of information for understanding clinical practice. Secondary usage of clinical data enables learning and service quality improvement. We present some insights from explorative data analysis for interpreting the records of patients referred for hyperkinetic disorders. The major challenges were data preparation, pre-analysis, imputation, and validation. We summarize the main characteristics, spot anomalies, and detect errors. The results include observations about the patient referral diversity based on 12 different variables. We modeled the activities in an individual episode of care, described our clinical observations among data, and discussed the challenges of data analysis.

According to a growing body of neurobiological evidence, the core symptoms of borderline personality disorder (BPD) may be linked to an opioidergic imbalance between the hedonic and stimulatory activity of mu opioid receptors (MOR) and the reward system inhibiting effects of kappa opioid receptors (KOR). Childhood trauma (CT), which is etiologically relevant to BPD, is also likely to lead to epigenetic and neurobiological adaptations by extensive activation of the stress and endogenous opioid systems. In this study, we investigated the methylation differences in the promoter of the KOR gene (OPRK1) in subjects with BPD (N = 47) and healthy controls (N = 48). Comparing the average methylation rates of regulatorily relevant subregions (specified regions CGI-1, CGI-2, EH1), we found no differences between BPD and HC. Analyzing individual CG nucleotides (N = 175), we found eight differentially methylated CG sites, all of which were less methylated in BPD, with five showing highly interrelated methylation rates. This differentially methylated region (DMR) was found on the falling slope (5’) of the promoter methylation gap, whose effect is enhanced by the DMR hypomethylation in BPD. A dimensional assessment of the correlation between disease severity and DMR methylation rate revealed DMR hypomethylation to be negatively associated with BPD symptom severity (measured by BSL-23). Finally, analyzing the influence of CT on DMR methylation, we found DMR hypomethylation to correlate with physical and emotional neglect in childhood (quantified by CTQ). Thus, the newly identified DMR may be a biomarker of the risks caused by CT, which likely epigenetically contribute to the development of BPD.

Introduction Major Depressive Disorder (MDD) is associated with a high burden of disease and notable economic costs. Standard treatments (e.g. medication or cognitive therapy) have been shown to be effective, but some patients remain unresponsive. With the knowledge that MDD patients have been shown to display an attentional cognitive bias towards negative stimuli, Cognitive Bias Modification (CBM)-training to focus attention on positive information is thought to improve emotional processing and depressive symptoms. Some studies imply reduced duration and occurrence of microstate D in MDD compared to healthy controls. However, the effect of CBM on microstates is still unclear. Objectives (1) To replicate previous findings that duration and occurrence of microstate D is reduced in patients with MDD compared to healthy controls in an independent sample and (2) to investigate the effect of an active CBM-training versus a control-training on microstates and its association with symptom improvements. Methods Thirty patients receiving outpatient treatment with MDD according to DSM V (aged 18-60) will be recruited in Essen and Aachen. The control group will consist of 30 healthy age-and-sex-matched participants. Psychological testing will be administered and all participants will be randomized to either an active or a control training. During the next visit, resting state EEG and a GoNoGo Task with positive, neutral and negative pictures will be measured. The participants will take a tablet home to undergo 10 sessions of CBM within 14 days. The training will be consisted of a dot-probe-task. In the active condition the probe will be more likely to appear behind a positive versus a neutral picture, while appearing randomly in the control condition. After 14 days, a second EEG will be recorded. Results Differences in duration and occurrence of microstate D between patients and healthy controls will be analyzed by conducting ANCOVAs with age and sex as covariates. ANCOVAs for repeated measurements will be calculated to study effects of time (pre- vs. post-training) and group (patients vs. healthy controls in active training; patients in active vs. patients in control-training), on duration and occurrence of microstate D. Conclusions CBM-training is proposed to be an effective treatment option for MDD patients, reflected in a reduced topographical bias of microstate D in EEG. Disclosure of Interest None Declared