Biobank of Psychiatric Diseases Mannheim – BioPsy

High quality biomaterial from patients and controls is a core prerequisite for research into the biological causes of mental disorder. BioPsy is the biobank of the Department of Genetic Epidemiology in Psychiatry at the Central Institute of Mental Health in Mannheim, Germany, and one of the largest psychiatric disorder biobanks worldwide. Here, ongoing collection is in progress for blood, DNA, mRNA, plasma, serum, saliva, urine, hair, and other biomaterials. Reuse of samples is permitted in a collaboration-based context. BioPsy operates according to German and European quality and data privacy standards.


Project description
The Department of Genetic Epidemiology in Psychiatry explores the genetic basis of mental disorders occurring across the entire lifespan. The aims of this research are to: (i) make decisive contributions to understanding the underlying molecular-pathogenic mechanisms; (ii) facilitate the development of a biologically-guided classification system; and (iii) enhance precision medicine within the field of mental health. The Department studies a broad range of mental disorders, such as bipolar disorder, major depression, schizophrenia, the autism spectrum disorders, attention deficit hyperactivity disorder, personality disorders, and addiction disorders, as well as co-morbid somatic conditions. Other research foci include investigation of the genetic basis of response to therapy (pharmacogenetics), and analysis of the role of gene-environment and gene-gene interactions in the development of mental disorder. This work involves the decoding of the genetic basis of complex endophenotypes, such as personality dimensions and correlates of neuronal plasticity. In terms of its contribution to public health, the Department is engaged in an ongoing process of attempting to develop prevention strategies for mental disorders on the basis of biological parameters.
A core prerequisite for research into the biological causes of mental disorders is the availability of appropriate biomaterials. The Department has a state-of-the-art Molecular Genetic Laboratory, and this is responsible for the biobanking of blood, DNA, mRNA, plasma, serum, and other biomaterials. The facility operates a laboratory information management system (LIMS); a controlled automated liquid-handling system; and an automated DNA/RNA extraction system. All samples are processed according to state-of-the art biobanking guidelines and standard procedures, and are stored in the Department's Biobank of Psychiatric Diseases (BioPsy, https://www. zi-mannheim.de/biobank). Figure 1 provides an overview of the biobank workflow. Since its establishment, the BioPsy bioresource has been used by the Dept. of Genetic Epidemiology in Psychiatry, by diverse collaboration partner and in large consortia, and has contributed to more than 280 peer reviewed publications.
This biobank contains biomaterials from all patients, relatives, and controls recruited by the Department and its collaboration partners, and expansion of the collection is ongoing.

Species
Human.

Steps
BioPsy collects biospecimens according to Standard Operating Procedures (SOPs), which are available upon request (www.zi-mannheim.de/biobank). The facility operates a laboratory information management system (LIMS); a controlled automated liquid-handling system; and an automated DNA/RNA extraction system. Access to biospecimens is possible in collaboration with the responsible principal investigators. Requests for access should be forwarded to the BioPsy manager. Table 1 provides an overview of collected biospecimen.

Stabilization/preservation
• Peripheral blood in EDTA (for plasma and DNA preparation) • Peripheral blood in PAXgene ® (PreAnalytiX GmbH tubes for RNA preparation) • Peripheral blood in CPT TM (Cell Preparation Tube) Sodium Citrate (Becton Dickinson, for PBMC preparation; PBMC = peripheral blood mononuclear cell) • Peripheral blood in CAT (Clot Activator Tube for serum preparation) • Saliva in Oragene TM (DNA Genotek Inc., for DNA preparation) • Cell lines in DMSO (Dimethyl sulfoxide) and Medium (for cryopreservation)

Type of long-term preservation
Freezing. All samples are stored in locked, temperaturemonitored freezers, and are accessible by BioPsy personnel only.

Quality assurance measures
All BioPsy procedures are subject to rigorous quality control. The principal measures for ensuring sample quality include procedures to: • Guarantee the integrity of nucleic acids using NanoDrop 1000 (peqlab); infinite M200PRO (Tecan); 2100 Bioanalyzer (Agilent Technologies); and agarose gel analysis • Ensure immediate intervention in the event of a power-cut and thus safeguard samples through use of appropriate alarm systems for all freezers • Up-date local and online databases Source of associated data -Extensive phenotypic assessment, including data from questionnaires, psychopathology evaluation, psychometry, (functional) magnetic resonance imaging -Clinical records In accordance with data protection guidelines and laws, no personal, phenotypic-, genetic-, or clinical data are stored in the biobank.
Phenotypic and genetic data are stored in secured environments, in separate dedicated data bases. This involves fine grained data access control for authorized personnel only.
Data are stored in pseudonymized form without personally identifiable information. Personal data are saved in a closed environment and are not accessible over network.

Ethics Statement
BioPsy applies appropriate ethical and data security measures on various levels: The clinicians who were responsible for subject recruitment evaluate all access requests to ensure compliance with the respective informed consent documentation. If indicated, the opinion of the respective ethics committee is also requested.
Biomaterial collection for scientific medical research is approved by the Medical Ethics Committee II of the Medical Faculty Mannheim/Heidelberg University, and the ethics committees of the collaborating recruiting centers.

(3) Bioresource description Object name
Biobank of Psychiatric Diseases Mannheim.

Bioresource location
Dept. of Genetic Epidemiology in Psychiatry, Molecular Genetic Laboratory, Central Institute of Mental Health (CIMH), Mannheim, Germany.

Identifier used
All samples are barcoded in accordance with universal standard identifier standards.

Bioresource type
Disease-based, epidemiological samples, and control samples.

Type of sampling
Population, family, disease based, longitudinal cohorts, sampled in clinical care, sampled in a research protocol context.

Disease status of patients/source
Psychiatric Diseases.

Clinical characteristics of patients/source
Patients and probands stem from various projects, each of which has specific characteristics.

Size of the bioresource
To date, approximately 180,000 biospecimens from around 78,000 individuals have been collected within 56 ongoing projects. The average sample accrual is 16,000 per year. The average number of requested samples is 9,000 per year.

Vital state of patients/source
Alive at the time of sampling.

Clinical diagnosis of patients/source
Psychiatric Diseases: e.g., Major Depression, Schizophrenia, Bipolar Disorder, Substance Use Disorders, Personality Disorders, Attention Deficit and Hyperactivity Disorder, Autism Spectrum Disorders, Dementia.

Control samples
Controls are either population based or selected according to project-specific criteria.

Access criteria
External collaborators are granted access to samples and/ or data after the provision of consent by the respective principle investigators and the manager of BioPsy, who must be contacted directly by the applicant. A prerequisite for access is that the intended research is compatible with the respective informed consent documentation. Compatibility with the informed consent is evaluated by the recruiting clinician, who might also request the opinion of the Ethical Committee. Reimbursement for shipping expenses may be required.
(4) Reuse potential Sample and/or data may be reused for further laboratory and/or data analyses, replication of previous findings, or meta-analyses. Reuse is possible on a collaborative basis, with the permission of the respective principle investigators and the manager of BioPsy, who must be contacted directly by the applicant.