Schizophrenia (Sz) and major depression (MD) are increasingly conceptualized as disorders with clinically relevant neuroimmune contributions. Recent evidence indicates activation of the innate immune system (e.g., elevated neutrophil and monocyte counts) in association with symptom severity. In parallel, emerging work suggests blood–brain barrier (BBB) dysfunction and episodes of neuroaxonal injury, measurable via increased neurofilament light chain (NfL). At the same time, reparative mechanisms—potentially reflected by insulin-like growth factor-binding protein 2 (IGFBP2)—may counteract neurodestructive processes, and the balance between NfL and IGFBP2 appears informative for short- and long-term outcomes.
In subproject JE4, we are investigating the mechanistic links between (i) innate immune activation, (ii) potential peripheral triggers such as increased gut permeability (“leaky gut”), (iii) BBB disruption, and (iv) neurodestruction/repair in Sz and—focusing on atypical MD—in depressive disorders. Using a longitudinal design across the Magdeburg and Jena sites, we will characterize neutrophil and monocyte function (e.g., phagocytosis, oxidative burst, activation marker expression) and inflammatory profiles (multiplex cytokine measurements). In addition, we will quantify blood-based markers of gut permeability (e.g., zonulin, I‑FABP, LBP), BBB integrity (e.g., GFAP, FABP7), and neurodestruction/repair (NfL and IGFBP2 using ultra-sensitive SIMOA technology). These laboratory measures will be integrated with advanced neuroimaging, including 3T dynamic contrast-enhanced MRI (DCE‑MRI) to detect subtle BBB leakage and state-of-the-art fibre-tract and connectivity analyses. Data integration will be performed jointly with WP2 and the neuroimaging projects JE1/JE2; the Jena site will additionally examine metabolic dysregulation and the gut microbiome as moderators of low-grade inflammation–brain circuit relationships, particularly in affective disorders.
The overarching aim is to delineate shared versus disorder-specific neuroimmune pathways, establish a robust DCE‑MRI protocol for BBB integrity assessment, and derive biomarker signatures that enable patient stratification and pave the way for more personalized, immune-informed interventions in Sz and atypical MD.

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Cognitive flexibility allows individuals to adapt their thoughts and behavior to changing situations, whereas cognitive rigidity leads to inflexible responses and heightened vulnerability to stress. Uncertainty, while a normal part of life, can become distressing when chronic, promoting anxiety, worry, and avoidance. Cognitive flexibility and uncertainty tolerance are closely linked in mental health, as flexibility supports adaptive coping under unpredictability, while rigidity exacerbates anxiety and maladaptive behaviors. Low flexibility and intolerance of uncertainty contribute to mood and anxiety disorders, whereas resilience is associated with greater adaptability. These processes rely on overlapping brain regions such as the prefrontal cortex, anterior cingulate cortex, insula, and amygdala. The project investigates these relationships in mice, examining environmental risk factors, underlying neural mechanisms, and whether cognitive flexibility training can improve uncertainty tolerance.

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The LIN and the Department of Psychiatry and Psychotherapy at Magdeburg University Hospital have launched the joint "PsychCircuits" initiative. This partnership aims to integrate the latest research findings directly into clinical practice and patient care. With the vision of sustainably improving the mental health of the population, PsychCircuits focuses on optimizing treatment and prevention strategies based on basic scientific research. The initiative aims to explore brain processes of mental health conditions to improve treatment approaches for people of all ages. PsychCircuits utilizes advanced imaging technologies, circuit research, state-of-the-art omics techniques and artificial intelligence. Through transdisciplinary collaboration in the areas of neuroplasticity, resilience, immunology, genetics and transcriptomics, innovative solutions are developed that directly inform clinical practice.
This text was translated with DeepL on 05/02/2026

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The service project Z01 aims to provide state-of-the-art tools for the interrogation of neurocognitive circuits at the synaptic, cellular and circuit level. With this approach we try to bridge investigations from the micro to the macroscale. Given the undisputed necessity to identify engram cells and their neuronal ensembles in order to identify neuronal resource and hidden potential, the CRC1436 has decided to devote the Z01-project to engram technology and neural activity tracing in combination with spatial transcriptomics. Z01 is therefore intimately connected with all subprojects dealing with animal experimentation. Z01 has established a platform of engram technologies where participating labs have profited from the established tools and – critically - from the steadily accumulating expertise of all users. In the first funding period Z01 has constantly updated its method portfolio with novel technology upon request by and in close coordination with the members of this CRC. We extend our approach by providing access to spatial transcriptomics, which will resolve the complex spatial organization of cell types and their connectivity in a neurocognitive circuit for many projects of this CRC.

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The micro- and macro-architecture of our brain sets biological limits for the performance of memory, attention and learning ability. However, there is great variability within these limits, and individual cognitive abilities can be improved through specific training. The aim of our research network is to develop verifiable theories on the performance limits of the human brain and to investigate methods for improving performance. We want to understand which neurobiological principles limit cognitive resources and how these resources can be fully developed or even increased. In doing so, we aim to identify new ways of using targeted interventions to develop and preserve neural resources across the lifespan.
This text was translated with DeepL on 29/12/2025

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The Cognitive Vitality research initiative has set itself the goal of minimizing the consequences of declining mental performance for society, the healthcare system and each individual. The combination of numerous areas of expertise beyond the neurosciences and the research location of Magdeburg gives us an almost infinite toolbox to grow beyond ourselves and tackle the problem of cognitive impairment holistically.
This text was translated with DeepL on 07/04/2026

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DZPG-CIRC is a network for research into maladaptive neural networks and their intervention in mental illness. The partners include Otto von Guericke University Magdeburg (OvGU), Magdeburg University Hospital (UMMD), the Leibnitz Institute of Neurobiology Magdeburg (LIN), Jena University Hospital (UKJ), Friedrich Schiller University Jena (FSU) and Martin Luther University Halle-Wittenberg (MLU),
This text was translated with DeepL on 27/03/2026

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