Integrated Understanding of Causes and Mechanisms in Mental Disorders

Understanding of the causes and complex developmental mechanisms of the common neuropsychiatric diseases remains incomplete. In recent years, systematic molecular genetic investigations have identified the first genes. The IntegraMent Consortium (Integrated Understanding of Causes and Mechanisms in Mental Disorders) will apply an integrated approach to elucidate the causal biological pathways and networks, and make a decisive contribution to deciphering the etiological mechanisms. Associated genetic variants and candidate genes will be identified using exome/genome-wide sequence approaches and state-of-the-art biostatistical methods. The effects of these genetic/epigenetic factors on symptom clusters and basal neuropsychological/cognitive processes will be investigated in large patient cohorts, which have been subjected to detailed symptom- and endophenotype characterization. Functional magnetic resonance imaging investigations will be used to demonstrate these effects on basal processes in vivo. Existing population-based samples in Germany will be used to perform epidemiological investigations of health risks and comorbidities, as well as gene-environment interactions. On the basis of the genetic findings, disease mechanisms will be addressed on the experimental level through investigations of protein-protein interactions, the introduction of human mutations into mouse models, and the establishment of induced human stem cells with a high-risk background. Using a systems biology approach, data from diverse experimental levels will be integrated and disease mechanisms will be modeled. The internationally networked IntegraMent Consortium will make a decisive contribution to advancements in our understanding of the biological basis of psychiatric illness, and important steps towards the translation of research findings into patient care.

Subprojects in IntegraMent:

SP 1   Data integration and systems modeling in mental disorders

SP 2   Central patient resource and bridging between genotype and phenotype

SP 3   Large-scale molecular genetic studies

SP 4   Transdiagnostic neurocognitive biomarkers for the major psychoses

SP 5   Impact of genetic risk factors for major psychiatric disease on mental and somatic pathology and resilience in the general population

SP 6   Epigenetics and transcriptome plasticity in psychiatric diseases

SP 7   Identification of disease mechanisms for major psychiatric disorders using genetic mouse models

SP 8   Interactome networks and perturbed cellular functions in schizophrenia and bipolar disorder

SP 9   Human iPS cell-based neuronal cultures for modeling neuropsychiatric disease

SP 10 Neurodynamic analysis of psychiatric disease mechanisms using computational network models

SP 11  Project management and graduate training

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