Munchen, Germany

The Max Planck Institute of Psychiatry is a scientific institute based in Munich, Germany specializing in Psychiatry. Currently directed by Elisabeth Binder, Alon Chen and Martin Keck, it is one of the 81 institutes in the Max Planck Society . Wikipedia.


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Gaali S.,Max Planck Institute of Psychiatry | Gaali S.,Lead Discovery Center GmbH | Gaali S.,Max Planck Institute of Biochemistry
Nature chemical biology | Year: 2015

The FK506-binding protein 51 (FKBP51, encoded by the FKBP5 gene) is an established risk factor for stress-related psychiatric disorders such as major depression. Drug discovery for FKBP51 has been hampered by the inability to pharmacologically differentiate against the structurally similar but functional opposing homolog FKBP52, and all known FKBP ligands are unselective. Here, we report the discovery of the potent and highly selective inhibitors of FKBP51, SAFit1 and SAFit2. This new class of ligands achieves selectivity for FKBP51 by an induced-fit mechanism that is much less favorable for FKBP52. By using these ligands, we demonstrate that selective inhibition of FKBP51 enhances neurite elongation in neuronal cultures and improves neuroendocrine feedback and stress-coping behavior in mice. Our findings provide the structural and functional basis for the development of mechanistically new antidepressants.


Martins-de-Souza D.,Max Planck Institute of Psychiatry
Journal of Psychiatric Research | Year: 2010

Despite all the efforts regarding the treatment of schizophrenia patients and the growing advances in molecular diagnosis studies, the biochemical basis of this debilitating psychotic mental disorder that affects approximately 1% of the world's population is still not completely comprehended. Several recent clinical and molecular studies, using transcriptome and proteome analyses (TPA), for example, have described the oligodendrocyte dysfunction as a significant feature of the disease. TPA has been extensively used as a biomarker discovery tool, but a detailed and careful interpretation of the generated data can also provide a picture of the integrated biochemical systems that lead to the disease. This review presents the oligodendrocyte role players in schizophrenia pathogenesis as revealed by transcriptome and proteome studies. The presented data contribute to the composition of a scenario that may lead to a better understanding of schizophrenia pathogenesis. © 2009 Elsevier Ltd.


Menke A.,Max Planck Institute of Psychiatry
International Review of Psychiatry | Year: 2013

While antidepressant therapy is an essential treatment of major depression, a substantial group of treated patients do not respond to therapy, or suffer from severe side effects. Moreover, the time of onset of the clinical improvement is often delayed. Antidepressants as currently available usually enhance serotonergic, noradrenergic and dopaminergic neurotransmission and may contribute to the inadequate remission rates for major depression. Therefore biomarkers enabling the identification of subgroups of patients and also finding unprecedented targets would provide the basis for personalized medication and thus improve treatment efficacy and reduce side effects. Several pharmacogenetic studies on antidepressant treatment response using single nucleotide polymorphism (SNPs) mapping have been performed but provided only modest findings. Therefore the analysis of gene expression to integrate genomic activity and environmental effects promises a new approach to cope with the complexity of factors influencing antidepressant treatment. Here gene expression studies focusing on candidate genes and genome-wide approaches using RNA derived from peripheral blood cells are reviewed. The most promising findings exist for hypothalamic-pituitary-adrenal (HPA) axis, inflammation and neuroplasticity related genes. However, straightforward translation into tailored treatment is still unlikely. Contradictory results limit the clinical use of the findings. Future studies are necessary, which could include functional analysis and consider gene-environment interactions. © 2013 Institute of Psychiatry.


Gaali S.,Max Planck Institute of Psychiatry
Nature Chemical Biology | Year: 2014

The FK506-binding protein 51 (FKBP51, encoded by the FKBP5 gene) is an established risk factor for stress-related psychiatric disorders such as major depression. Drug discovery for FKBP51 has been hampered by the inability to pharmacologically differentiate against the structurally similar but functional opposing homolog FKBP52, and all known FKBP ligands are unselective. Here, we report the discovery of the potent and highly selective inhibitors of FKBP51, SAFit1 and SAFit2. This new class of ligands achieves selectivity for FKBP51 by an induced-fit mechanism that is much less favorable for FKBP52. By using these ligands, we demonstrate that selective inhibition of FKBP51 enhances neurite elongation in neuronal cultures and improves neuroendocrine feedback and stress-coping behavior in mice. Our findings provide the structural and functional basis for the development of mechanistically new antidepressants. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Schmidt M.V.,Max Planck Institute of Psychiatry
Psychoneuroendocrinology | Year: 2011

Early life stress is one of the best characterized risk factors for psychiatric disorders, including depression, and many animal models have therefore studied the long-term physiological and behavioural consequences of early life stress. In most approaches a very deterministic view of adverse experiences early in life prevails, linking these events inevitably with later pathology. By summarizing literature on early life programming and adaptive phenotypic plasticity the current review proposes that early life challenges may induce changes that prepare an individual for life in a more hostile environment and are therefore predominantly beneficial. Adult diseases as depression might thus not be promoted by early life adversity per se, but by a mismatch of the programmed and the later actual environment in combination with a more vulnerable or resilient genetic predisposition. The present review further discusses the ability of currently available animal models for depression to investigate this novel hypothesis. Finally, a number of criteria and research strategies are outlined that would be necessary to address the mismatch hypothesis of depression. © 2010 Elsevier Ltd.


Hausch F.,Max Planck Institute of Psychiatry
Angewandte Chemie - International Edition | Year: 2013

New members in the GPCR photo gallery! Crystal structures of class B G protein-coupled receptors, which bind peptide hormones, have been solved [see picture of the corticotropin-releasing factor receptor 1 (blue) and a bound allosteric nonpeptide antagonist (green)]. The structures provide a basis for a rational design of better drugs for diabetes, osteoporosis, migraine, or depression. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Issler O.,Weizmann Institute of Science | Issler O.,Max Planck Institute of Psychiatry | Chen A.,Weizmann Institute of Science | Chen A.,Max Planck Institute of Psychiatry
Nature Reviews Neuroscience | Year: 2015

Recent studies have revealed that patients with psychiatric disorders have altered microRNA (miRNA) expression profiles in the circulation and brain. Furthermore, animal studies have shown that manipulating the levels of particular miRNAs in the brain can alter behaviour. Here, we review recent studies in humans, animal models, cellular systems and bioinformatics that have advanced our understanding of the contribution of brain miRNAs to the regulation of behaviour in the context of psychiatric conditions. These studies highlight the potential of miRNA levels to be used in the diagnosis of psychiatric disorders and suggest that brain miRNAs could become novel treatment targets for psychiatric disorders. © 2015 Macmillan Publishers Limited. All rights reserved.


Zhang Y.,Max Planck Institute of Psychiatry
Molecular & cellular proteomics : MCP | Year: 2011

Depression and anxiety disorders affect a great number of people worldwide. Whereas singular factors have been associated with the pathogenesis of psychiatric disorders, growing evidence emphasizes the significance of dysfunctional neural circuits and signaling pathways. Hence, a systems biology approach is required to get a better understanding of psychiatric phenotypes such as depression and anxiety. Furthermore, the availability of biomarkers for these disorders is critical for improved diagnosis and monitoring treatment response. In the present study, a mouse model presenting with robust high versus low anxiety phenotypes was subjected to thorough molecular biomarker and pathway discovery analyses. Reference animals were metabolically labeled with the stable (15)N isotope allowing an accurate comparison of protein expression levels between the high anxiety-related behavior versus low anxiety-related behavior mouse lines using quantitative mass spectrometry. Plasma metabolomic analyses identified a number of small molecule biomarkers characteristic for the anxiety phenotype with particular focus on myo-inositol and glutamate as well as the intermediates involved in the tricarboxylic acid cycle. In silico analyses suggested pathways and subnetworks as relevant for the anxiety phenotype. Our data demonstrate that the high anxiety-related behavior and low anxiety-related behavior mouse model is a valuable tool for anxiety disorder drug discovery efforts.


Steiger A.,Max Planck Institute of Psychiatry
Pharmacopsychiatry | Year: 2013

In patients with depression, characteristic changes of sleep electroencephalogram and nocturnal hormone secretion occur including rapid eye movement (REM) sleep disinhibition, reduced non-REM sleep and impaired sleep continuity. Neuropeptides are common regulators of the sleep electroencephalogram (EEG) and nocturnal hormone secretion and changes in their activity appear to contribute to the aberrances of sleep in affective disorders. A reciprocal interaction of the sleep-promoting growth hormone-releasing hormone (GHRH) and corticotrophin-releasing hormone (CRH), which promotes wakefulness and REM sleep, plays a key role in sleep regulation, at least in male subjects. Also galanin and ghrelin promote sleep in men. Neuropeptide Y is involved in the timing of sleep onset. The effects of peptides of sleep are influenced by the time of administration, age, gender and depression. In healthy subjects and in remitted depressed patients motoric memory learning is consolidated during sleep. This effect is absent in depressed patients who are at least 30 years old, and is probably related to elevated glucocorticoid levels. © Georg Thieme Verlag KG Stuttgart · New York.


Czeh B.,Max Planck Institute of Psychiatry | Di Benedetto B.,Max Planck Institute of Psychiatry
European Neuropsychopharmacology | Year: 2013

Post-mortem histopathological studies report on reduced glial cell numbers in various frontolimbic areas of depressed patients implying that glial loss together with abnormal functioning could contribute to the pathophysiology of mood disorders. Astrocytes are regarded as the most abundant cell type in the brain and known for their housekeeping functions, but as recent developments suggest, they are also dynamic regulators of synaptogenesis, synaptic strength and stability and they control adult hippocampal neurogenesis. The primary aim of this review was to summarize the abundant experimental evidences demonstrating that antidepressant therapies have profound effect on astrocytes. Antidepressants modify astroglial physiology, morphology and by affecting gliogenesis they probably even regulate glial cell numbers. Antidepressants affect intracellular signaling pathways and gene expression of astrocytes, as well as the expression of receptors and the release of various trophic factors. We also assess the potential functional consequences of these changes on glutamate and glucose homeostasis and on synaptic communication between the neurons. We propose here a hypothesis that antidepressant treatment not only affects neurons, but also activates astrocytes, triggering them to carry out specific functions that result in the reactivation of cortical plasticity and can lead to the readjustment of abnormal neuronal networks. We argue here that these astrocyte specific changes are likely to contribute to the therapeutic effectiveness of the currently available antidepressant treatments and the better understanding of these cellular and molecular processes could help us to identify novel targets for the development of antidepressant drugs. © 2012 Elsevier B.V. and ECNP.

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