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BACKGROUND AND HYPOTHESIS: Non-affective psychoses (NAP) are associated with severe consequences with regard to social functioning, physical health, employment, and suicidality. Treatment guidelines recommend cognitive behavioral therapy for psychosis (CBTp) as an effective additional treatment strategy to psychopharmacology. We hypothesized that outpatient CBTp has an add-on effect in individuals with NAP who already receive comprehensive outpatient care (COC) in Germany. STUDY DESIGN: In a randomized-controlled effectiveness trial, 6 months of COCâ +â CBTp were compared to COC. The primary outcomes were change of symptom severity as assessed by the Positive and Negative Symptom Scale (pre-/post-treatment and 6-month follow-up). Mixed linear models and effect sizes were used to compare changes across treatment groups. Additionally, the number of readmissions was compared. STUDY RESULTS: Nâ =â 130 individuals with chronic NAP were recruited (COCâ +â CBTp: nâ =â 64, COC: nâ =â 66). COCâ +â CBTp participants significantly improved more regarding positive symptom severity (estimated mean difference at follow-up: -2.33, 95% CI: -4.04 to -0.61, Pâ =â .0083, dâ =â 0.32) and general psychopathology (estimated mean difference at follow-up: -4.55, 95% CI: -7.30 to -1.81, Pâ =â .0013, dâ =â 0.44) than the COC group. In both groups, negative symptom severity did not change significantly over time nor did groups differ regarding readmissions. CONCLUSION: The results underline an add-on benefit of CBTp in chronically ill individuals with NAP. Superiority of CBTp was demonstrated in comparison with high-quality comprehensive care and may also be true in different comprehensive care settings. CLINICAL TRIALS REGISTRATION: DRKS00015627.
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OBJECTIVE: The innovation fund project DemStepCare aimed to optimize multi-professional care through case management, risk stratification, and crisis outpatient clinic. Here, the evaluation results from the perspective of the general practitioners are presented. METHODS: A quantitative survey was carried out at three time points regarding acceptance, benefit assessment and sensitivity to dementia of the general practitioners. In addition, qualitative interviews were conducted. RESULTS: Satisfaction with the overall project was high. Added value and relief factors were perceived and more effective and stable dementia care was achieved through collaboration with case management. Physicians reported increased subjective competence in diagnostics and disease management. CONCLUSIONS: The results confirm the benefit and effectiveness of DemStepCare from general practitioner's perspective.
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Family support in Germany is provided by a conglomerate of different support systems. In order to optimize the networking and cooperation of these inter-institutional support systems, it is important to gain a deeper understanding of the existing cooperation structures. Against this background, different qualitative and quantitative aspects were surveyed and analyzed by means of a questionnaire among participants from different help systems. The results point in particular to the currently existing special role of adult psychiatry.
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Psiquiatria do Adolescente , Proteção da Criança , Humanos , Criança , Adulto , Adolescente , Alemanha , Inquéritos e QuestionáriosRESUMO
The network of thymic stromal cells provides essential niches with unique molecular cues controlling T cell development and selection. Recent single-cell RNA sequencing studies have uncovered previously unappreciated transcriptional heterogeneity among thymic epithelial cells (TEC). However, there are only very few cell markers that allow a comparable phenotypic identification of TEC. Here, using massively parallel flow cytometry and machine learning, we deconvoluted known TEC phenotypes into novel subpopulations. Using CITEseq, these phenotypes were related to corresponding TEC subtypes defined by the cells' RNA profiles. This approach allowed the phenotypic identification of perinatal cTEC and their physical localisation within the cortical stromal scaffold. In addition, we demonstrate the dynamic change in the frequency of perinatal cTEC in response to developing thymocytes and reveal their exceptional efficiency in positive selection. Collectively, our study identifies markers that allow for an unprecedented dissection of the thymus stromal complexity, as well as physical isolation of TEC populations and assignment of specific functions to individual TEC subtypes.
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Células Epiteliais , Timócitos , Feminino , Gravidez , Humanos , Diferenciação Celular , Sinais (Psicologia) , RNARESUMO
The thymus medulla is a key site for immunoregulation and tolerance, and its functional specialisation is achieved through the complexity of medullary thymic epithelial cells (mTEC). While the importance of the medulla for thymus function is clear, the production and maintenance of mTEC diversity remains poorly understood. Here, using ontogenetic and inducible fate-mapping approaches, we identify mTEC-restricted progenitors as a cytokeratin19+ (K19+) TEC subset that emerges in the embryonic thymus. Importantly, labelling of a single cohort of K19+ TEC during embryogenesis sustains the production of multiple mTEC subsets into adulthood, including CCL21+ mTEClo, Aire+ mTEChi and thymic tuft cells. We show K19+ progenitors arise prior to the acquisition of multiple mTEC-defining features including RANK and CCL21 and are generated independently of the key mTEC regulator, Relb. In conclusion, we identify and define a multipotent mTEC progenitor that emerges during embryogenesis to support mTEC diversity into adult life.
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Tolerância Imunológica , Queratina-19 , Timo , Animais , Camundongos , Diferenciação Celular , Células Epiteliais , Camundongos Endogâmicos C57BL , Células-TroncoRESUMO
Intrinsic and extrinsic cues determine developmental trajectories of hematopoietic stem cells (HSCs) towards erythroid, myeloid and lymphoid lineages. Using two newly generated transgenic mice that report and trace the expression of terminal deoxynucleotidyl transferase (TdT), transient induction of TdT was detected on a newly identified multipotent progenitor (MPP) subset that lacked self-renewal capacity but maintained multilineage differentiation potential. TdT induction on MPPs reflected a transcriptionally dynamic but uncommitted stage, characterized by low expression of lineage-associated genes. Single-cell CITE-seq indicated that multipotency in the TdT+ MPPs is associated with expression of the endothelial cell adhesion molecule ESAM. Stable and progressive upregulation of TdT defined the lymphoid developmental trajectory. Collectively, we here identify a new multipotent progenitor within the MPP4 compartment. Specification and commitment are defined by downregulation of ESAM which marks the progressive loss of alternative fates along all lineages.
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DNA Nucleotidilexotransferase , Células-Tronco Hematopoéticas , Células-Tronco Multipotentes , Animais , Diferenciação Celular , Linhagem da Célula/genética , DNA Nucleotidilexotransferase/genética , DNA Nucleotidilexotransferase/metabolismo , Células-Tronco Hematopoéticas/fisiologia , Camundongos , Camundongos TransgênicosRESUMO
The transcription factor FOXN1 is a master regulator of thymic epithelial cell (TEC) development and function. Here, we demonstrate that FOXN1 expression is differentially regulated during organogenesis and participates in multimolecular nuclear condensates essential for the factor's transcriptional activity. FOXN1's C-terminal sequence regulates the diffusion velocity within these aggregates and modulates the binding to proximal gene regulatory regions. These dynamics are altered in a patient with a mutant FOXN1 that is modified in its C-terminal sequence. This mutant is transcriptionally inactive and acts as a dominant negative factor displacing wild-type FOXN1 from condensates and causing athymia and severe lymphopenia in heterozygotes. Expression of the mutated mouse ortholog selectively impairs mouse TEC differentiation, revealing a gene dose dependency for individual TEC subtypes. We have therefore identified the cause for a primary immunodeficiency disease and determined the mechanism by which this FOXN1 gain-of-function mutant mediates its dominant negative effect.
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Depression is associated with abnormalities in patterns of information processing, particularly in the context of processing of interpersonal information. The present study was designed to investigate the differences in depressive individuals in cortical processing of facial stimuli when neutral faces were presented in a context that involved information about emotional valence as well as self-reference. In 21 depressive patients and 20 healthy controls, event-related potentials (ERPs) were recorded during the presentation of neutral facial expressions, which were accompanied by affective context information that was either self- or other-related. Across conditions, depressive patients showed larger mean P100 amplitudes than healthy controls. Furthermore, mean late positive potential (LPP) amplitudes of depressive patients were larger in response to faces in self-related than in other-related context. In addition, irrespective of self-reference, mean LPP responses of depressive patients to faces presented after socially threatening sentences were larger compared with faces presented after neutral sentences. Results regarding self-reference supported results of previous studies indicating larger mean amplitudes in self-related conditions. Findings suggest a general heightened initial responsiveness to emotional cues and a sustained emotion processing of socially threatening information in depressive patients.
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Depressão , Eletroencefalografia , Emoções , Potenciais Evocados , Expressão Facial , Feminino , HumanosRESUMO
Post-traumatic stress disorder (PTSD) is associated with alterations in cardiac reactivity to threat cues. Meta-analyses have summarized that adults with PTSD have increased heart rates in response to trauma-related stimuli. However, the opposite effect (i.e., cardiac hyporeactivity) has recently been reported in subgroups of PTSD patients. In children and adolescents with PTSD, reports of cardiac alterations are rare and ambiguous. So far, most studies in adolescents and young adults are restricted to victims of accidents, even though PTSD is highly prevalent in victims of child maltreatment. The present study aimed at investigating cardiac reactions in adolescents and young adults with PTSD after child abuse. Cardiac responses to standardized emotional words were studied in 39 adolescent and young adult PTSD patients after childhood sexual and/or physical abuse as compared to 39 healthy control subjects (age range: 15-20 years). The experimental paradigm consisted of a passive reading task with neutral, positive, physically threatening, and socially threatening (swear) words. Results showed that cardiac reactions to negative stimuli, particularly physically threatening stimuli, were less pronounced in PTSD patients than in controls. Moreover, cardiac reactions in response to socially threatening words were less variable in the PTSD group. No differences between and within groups were present in reaction to neutral or positive stimuli. Findings suggest that a physiologically blunted subtype of PTSD may already manifest during adolescence and young adulthood. Moreover, the results of the present study emphasize the relevance of individual trauma history for physiological reactions.
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Maus-Tratos Infantis , Emoções/fisiologia , Frequência Cardíaca/fisiologia , Trauma Psicológico/fisiopatologia , Leitura , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adolescente , Adulto , Eletrocardiografia , Feminino , Humanos , Masculino , Trauma Psicológico/complicações , Transtornos de Estresse Pós-Traumáticos/etiologia , Adulto JovemRESUMO
System-wide quantification of the cell surface proteotype and identification of extracellular glycosylation sites is challenging when samples are limited. Here, we miniaturize and automate the previously described Cell Surface Capture (CSC) technology, increasing sensitivity, reproducibility and throughput. We use this technology, which we call autoCSC, to create population-specific surfaceome maps of developing mouse B cells and use targeted flow cytometry to uncover developmental cell subpopulations.
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Subpopulações de Linfócitos B/classificação , Diferenciação Celular , Ensaios de Triagem em Larga Escala/métodos , Proteínas de Membrana/análise , Proteômica/métodos , Animais , Subpopulações de Linfócitos B/metabolismo , Membrana Celular/metabolismo , Citometria de Fluxo/métodos , Células HT29 , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Cultura Primária de Células , Reprodutibilidade dos TestesRESUMO
Post-traumatic stress disorder (PTSD) is associated with a hypersensitivity to potential threat. This hypersensitivity manifests through differential patterns of emotional information processing and has been demonstrated in behavioral and neurophysiological experimental paradigms. However, the majority of research has been focused on adult patients with PTSD. To examine possible differences in underlying neurophysiological patterns for adolescent patients with PTSD after childhood sexual and/or physical abuse (CSA/CPA), ERP correlates of emotional word processing in 38 healthy participants and 40 adolescent participants with PTSD after experiencing CSA/CPA were studied. The experimental paradigm consisted of a passive reading task with neutral, positive (e.g., paradise), physically threatening (e.g., torment), and socially threatening (i.e., swearing, e.g., son of a bitch) words. A modulation of P3 amplitudes by emotional valence was found, with positive words inducing less elevated amplitudes over both groups. Interestingly, in later processing, the PTSD group showed augmented early late positive potential (LPP) amplitudes for socially threatening stimuli, while there were no modulations within the healthy control group. Also, region-specific emotional modulations for anterior and posterior electrode clusters were found. For the anterior LPP, highest activations have been found for positive words, while socially and physically threatening words led to strongest modulations in the posterior LPP cluster. There were no modulations by group or emotional valence at the P1 and EPN stage. The findings suggest an enhanced conscious processing of socially threatening words in adolescent patients with PTSD after CSA/CPA, pointing to the importance of a disjoined examination of threat words in emotional processing research.
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Afeto/fisiologia , Viés de Atenção/fisiologia , Córtex Cerebral/fisiopatologia , Maus-Tratos Infantis , Potenciais Evocados/fisiologia , Medo/fisiologia , Leitura , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adolescente , Adulto , Eletroencefalografia , Potenciais Evocados P300/fisiologia , Feminino , Humanos , Masculino , Reconhecimento Visual de Modelos/fisiologia , Adulto JovemRESUMO
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants, characterized by lung growth arrest and matrix remodeling. Various animal models provide mechanistic insights in the pathogenesis of BPD. Since there is increasing evidence that genetic susceptibility modifies the response to lung injury, we investigated strain-dependent effects in hyperoxia (HYX)-induced lung injury of newborn mice. To this end, we exposed newborn C57BL/6N and C57BL/6J mice to 85% O2 (HYX) or normoxia (NOX; 21% O2) for 28 days, followed by lung excision for histological and molecular measurements. BL/6J-NOX mice exhibited a lower body and lung weight than BL/6N-NOX mice; hyperoxia reduced body weight in both strains and increased lung weight only in BL/6J-HYX mice. Quantitative histomorphometric analyses revealed reduced alveolar formation in lungs of both strains after HYX, but the effect was greater in BL/6J-HYX mice than BL/6N-HYX mice. Septal thickness was lower in BL/6J-NOX mice than BL/6N-NOX mice but increased in both strains after HYX. Elastic fiber density was significantly greater in BL/6J-HYX mice than BL/6N-HYX mice. Lungs of BL/6J-HYX mice were protected from changes in gene expression of fibrillin-1, fibrillin-2, fibulin-4, fibulin-5, and surfactant proteins seen in BL/6N-HYX mice. Finally, Stat3 was activated by HYX in both strains; in contrast, activation of Smad2 was markedly greater in lungs of BL/6N mice than BL/6J mice after HYX. In summary, we demonstrate strain-dependent differences in lung structure and matrix, alveolar epithelial cell markers, and Smad2 (transforming growth factor ß) signaling in neonatal HYX-induced lung injury. Strain-dependent effects and genetic susceptibility need be taken into consideration for reproducibility and reliability of results in animal models.
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Hiperóxia/patologia , Pneumopatias/induzido quimicamente , Pulmão/patologia , Oxigênio/efeitos adversos , Fator de Transcrição STAT3/metabolismo , Proteína Smad2/metabolismo , Animais , Animais Recém-Nascidos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Oxigênio/administração & dosagem , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3/genética , Proteína Smad2/genéticaRESUMO
T cell development is critically dependent on successful rearrangement of antigen-receptor chains. At the ß-selection checkpoint, only cells with a functional rearrangement continue in development. However, how nonselected T cells proceed in their dead-end fate is not clear. We identified low CD27 expression to mark pre-T cells that have failed to rearrange their ß-chain. Expression profiling and single-cell transcriptome clustering identified a developmental trajectory through ß-selection and revealed specific expression of the transcription factor Duxbl at a stage of high recombination activity before ß-selection. Conditional transgenic expression of Duxbl resulted in a developmental block at the DN3-to-DN4 transition due to reduced proliferation and enhanced apoptosis, whereas RNA silencing of Duxbl led to a decrease in apoptosis. Transcriptome analysis linked Duxbl to elevated expression of the apoptosis-inducing Oas/RNaseL pathway. RNaseL deficiency or sustained Bcl2 expression led to a partial rescue of cells in Duxbl transgenic mice. These findings identify Duxbl as a regulator of ß-selection by inducing apoptosis in cells with a nonfunctional rearrangement.
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Proteínas de Homeodomínio/metabolismo , Linfócitos T/fisiologia , Fatores de Transcrição/metabolismo , Animais , Apoptose/genética , Feminino , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Linfócitos T/citologia , Timo/citologia , Fatores de Transcrição/genética , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismoRESUMO
Interleukin-7 (IL-7) and Flt3-ligand (FL) are two cytokines important for the generation of B cells, as manifested by the impaired B cell development in mice deficient for either cytokine or their respective receptors and by the complete block in B cell differentiation in the absence of both cytokines. IL-7 is an important survival and proliferation factor for B cell progenitors, whereas FL acts on several early developmental stages, prior to B cell commitment. We have generated mice constitutively over-expressing both IL-7 and FL. These double transgenic mice develop splenomegaly and lymphadenopathy characterized by tremendously enlarged lymph nodes even in young animals. Lymphoid, myeloid and dendritic cell numbers are increased compared to mice over-expressing either of the two cytokines alone and the effect on their expansion is synergistic, rather than additive. B cell progenitors, early progenitors with myeloid and lymphoid potential (EPLM), common lymphoid progenitors (CLP) and lineage-, Sca1+, kit+ (LSK) cells are all increased not only in the bone marrow but also in peripheral blood, spleen and even lymph nodes. When transplanted into irradiated wild-type mice, lymph node cells show long-term multilineage reconstitution, further confirming the presence of functional hematopoietic progenitors therein. Our double transgenic mouse model shows that sustained and combined over-expression of IL-7 and FL leads to a massive expansion of most bone marrow hematopoietic progenitors and to their associated presence in peripheral lymphoid organs where they reside and potentially differentiate further, thus leading to the synergistic increase in mature lymphoid and myeloid cell numbers. The present study provides further in vivo evidence for the concerted action of IL-7 and FL on lymphopoiesis and suggests that extramedullary niches, including those in lymph nodes, can support the survival and maintenance of hematopoietic progenitors that under physiological conditions develop exclusively in the bone marrow.
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Células-Tronco Hematopoéticas/imunologia , Interleucina-7/imunologia , Células Progenitoras Linfoides/imunologia , Proteínas de Membrana/imunologia , Células-Tronco Multipotentes/imunologia , Animais , Proliferação de Células/genética , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Expressão Gênica/imunologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Interleucina-7/genética , Interleucina-7/metabolismo , Células Progenitoras Linfoides/citologia , Células Progenitoras Linfoides/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Camundongos Transgênicos , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/metabolismoRESUMO
The escape of anti-self B cells from tolerance mechanisms like clonal deletion, receptor editing, and anergy results in the production of autoantibodies, which is a hallmark of many autoimmune disorders. In this study, we demonstrate that both germline sequences and somatic mutations contribute to autospecificity of B cell clones. For this issue, we investigated the development of antinuclear autoantibodies (ANAs) and their repertoire in two different mouse models. First, in aging mice that were shown to gain several autoimmune features over time including ANAs. Second, in mice undergoing a chronic graft-versus-host disease (GVHD), thereby developing systemic lupus erythematosus-like symptoms. Detailed repertoire analysis revealed that somatic hypermutations (SHM) were present in all Vh and practically all Vl regions of ANAs generated in these two models. The ANA B cell repertoire in aging mice was restricted, dominated by clonally related Vh1-26/Vk4-74 antibodies. In the collection of GVHD-derived ANAs, the repertoire was less restricted, but the usage of the Vh1-26/Vk4-74 combination was still apparent. Germline conversion showed that the SHM in the 4-74 light chain are deterministic for autoreactivity. Detailed analysis revealed that antinuclear reactivity of these antibodies could be induced by a single amino acid substitution in the CDR1 of the Vk4-74. In both aging B6 and young GVHD mice, conversion of the somatic mutations in the Vh and Vl regions of non Vh1-26/Vk4-74 using antibodies showed that B cells with a germline-encoded V gene could also contribute to the ANA-reactive B cell repertoire. These findings indicate that two distinct pathways generate ANA-producing B cells in both model systems. In one pathway, they are generated by Vh1-26/Vk4-74 expressing B cells in the course of immune responses to an antigen that is neither a nuclear antigen nor any other self-antigen. In the other pathway, ANA-producing B cells are derived from progenitors in the bone marrow that express B cell receptors (BCRs), which bind to nuclear antigens and that escape tolerance induction, possibly as a result of crosslinking of their BCRs by multivalent determinants of nuclear antigens.
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Envelhecimento/imunologia , Anticorpos Antinucleares/imunologia , Antígenos Nucleares/imunologia , Autoimunidade/genética , Linfócitos B/imunologia , Doença Enxerto-Hospedeiro/imunologia , Substituição de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Autoimunidade/imunologia , Histonas/imunologia , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação/genética , Receptores de Antígenos de Linfócitos B/imunologiaRESUMO
Hematopoietic cells are continuously generated throughout life from hematopoietic stem cells, thus making hematopoiesis a favorable system to study developmental cell lineage commitment. The main factors incorporating environmental signals to developing hematopoietic cells are cytokines, which regulate commitment of hematopoietic progenitors to the different blood lineages by acting either in an instructive or a permissive manner. Fms-like tyrosine kinase-3 (Flt3) ligand (FL) and Interleukin-7 (IL-7) are cytokines pivotal for B-cell development, as manifested by the severely compromised B-cell development in their absence. However, their precise role in regulating B-cell commitment has been the subject of debate. In the present study we assessed the rescue of B-cell commitment in mice lacking IL-7 but simultaneously overexpressing FL. Results obtained demonstrate that FL overexpression in IL-7-deficient mice rescues B-cell commitment, resulting in significant Ebf1 and Pax5 expression in Ly6D+CD135+CD127+CD19- precursors and subsequent generation of normal numbers of CD19+ B-cell progenitors, therefore indicating that IL-7 can be dispensable for commitment to the B-cell lineage. Further analysis of Ly6D+CD135+CD127+CD19- progenitors in IL-7- or FL-deficient mice overexpressing Bcl2, as well as in IL-7 transgenic mice suggests that both FL and IL-7 regulate B-cell commitment in a permissive manner: FL by inducing proliferation of Ly6D+CD135+CD127+CD19- progenitors and IL-7 by providing survival signals to these progenitors.
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Linfócitos B/citologia , Linfócitos B/imunologia , Linhagem da Célula/imunologia , Interleucina-7/metabolismo , Proteínas de Membrana/metabolismo , Animais , Antígenos CD19/metabolismo , Antígenos Ly/metabolismo , Linfócitos B/metabolismo , Proliferação de Células , Sobrevivência Celular , Feminino , Proteínas Ligadas por GPI/metabolismo , Hematopoese/imunologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Interleucina-7/deficiência , Interleucina-7/genética , Células Progenitoras Linfoides/citologia , Células Progenitoras Linfoides/imunologia , Células Progenitoras Linfoides/metabolismo , Masculino , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos TransgênicosRESUMO
Recent studies have shown that the perceptual processing of human faces is affected by context information, such as previous experiences and information about the person represented by the face. The present study investigated the impact of verbally presented information about the person that varied with respect to affect (neutral, physically threatening, socially threatening) and reference (self-referred, other-referred) on the processing of faces with an inherently neutral expression. Stimuli were presented in a randomized presentation paradigm. Event-related potential (ERP) analysis demonstrated a modulation of the evoked potentials by reference at the EPN (early posterior negativity) and LPP (late positive potential) stage and an enhancing effect of affective valence on the LPP (700-1000 ms) with socially threatening context information leading to the most pronounced LPP amplitudes. We also found an interaction between reference and valence with self-related neutral context information leading to more pronounced LPP than other related neutral context information. Our results indicate an impact of self-reference on early, presumably automatic processing stages and also a strong impact of valence on later stages. Using a randomized presentation paradigm, this study confirms that context information affects the visual processing of faces, ruling out possible confounding factors such as facial configuration or conditional learning effects.