Brief Summary The goal of this observational study is to establish a comprehensive biobank and phenotypic data repository for patients diagnosed with bipolar disorder in Türkiye. The study will prospectively collect standardized clinical, demographic, lifestyle, and biological data to create a secure genomic and epigenomic research resource.

The main questions it aims to answer are:

Can large-scale, standardized phenotypic and biological data collection improve the understanding of bipolar disorder subtypes and disease course?

Can integration of biobank samples with genomic and epigenomic analyses identify biomarkers that inform future diagnosis, prognosis, and treatment strategies?

Participants will:

Provide consent and demographic/clinical information using the NeuroPsyBiT Data Collector software.

Contribute blood samples (e.g., EDTA tubes) for DNA extraction, genotyping, and future epigenomic studies.

Allow secure storage of their data and biospecimens in the RTSGD biobank for use in ethically approved research projects.

All data and samples will be collected and stored under strict ethical oversight and in compliance with national (KVKK) and international (GDPR) data protection regulations. Personally identifiable information will not be shared, and access to the biobank and dataset will only be granted after approval by institutional review boards and ethics committees.

This registry will create the foundation for future genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS), supporting the long-term goal of developing precision psychiatry tools for bipolar disorder.

This project, NeuroPsyBiT-BD-001: Genomic & Epigenomic Biobank of Bipolar Disorder, is an observational patient registry designed to establish a large-scale biobank and standardized phenotypic data platform for individuals with bipolar disorder in Türkiye.

Objectives and Rationale:

Bipolar disorder (BD) is a chronic and heterogeneous psychiatric condition with high morbidity, relapse rates, and unmet clinical needs. Genetic and epigenetic factors are believed to play a central role in its pathogenesis, yet reliable biomarkers remain scarce. By combining deeply phenotyped clinical data with biological samples, this registry seeks to create a robust foundation for genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS). This approach will enable future biomarker discovery, stratification of subtypes, and exploration of treatment response predictors.

Study Design:

Population: Patients diagnosed with bipolar disorder according to DSM-5 criteria will be recruited through the NeuroPsyBiT consortium, a partnership between the Research and Treatment Society of Genetic Disorders (RTSGD) and the Department of Psychiatry at Selçuk University Medical Faculty.

Sample Size: The initial target is 500 patients in the first phase, with an expansion goal of ≥1,000 patients within one year.

Data Collection: Phenotypic and clinical data (>250 variables) will be systematically recorded using the NeuroCybe Data Collector, a proprietary software platform developed for standardized psychiatric data capture. Domains include demographics, medical/psychiatric history, clinical course, comorbidities, lifestyle/exposome, treatments, and psychometric assessments.

Biospecimen Collection: Blood samples (EDTA tubes) will be collected for DNA extraction, genotyping, and future methylation profiling. Samples will be processed and stored under ISO-compliant biobanking standards, ensuring traceability and long-term integrity.

Infrastructure and Data Security:

Biobank Management: RTSGD laboratories will serve as the central biobank facility, operating under internationally recognized quality standards for sample processing and storage.

Data Governance: All phenotypic and genotypic data will be securely stored on RTSGD on-premise servers with no cloud storage permitted.

Ethics & Privacy: Data handling will strictly comply with national (KVKK) and international (GDPR) regulations. Personally identifiable information will be de-identified. Data access will only be granted following approval by both institutional ethics committees and the Turkish Ministry of Health.

Future Access: De-identified datasets and biospecimens will be made available for national and international collaboration upon direct application to the consortium, subject to ethical approvals.

Scientific Impact:

This registry represents the first large-scale, ISO-standardized biobank for bipolar disorder in Türkiye. By unifying deep phenotyping with genomic and epigenomic resources, it will:

Enable high-resolution GWAS and EWAS in BD.

Provide a resource for cross-cohort meta-analysis and replication studies.

Facilitate translational research toward precision psychiatry approaches (diagnostic tools, risk stratification, and individualized treatment).

Create a sustainable national and international platform for collaboration in psychiatric genetics and epigenetics.

Long-term Vision:

The NeuroPsyBiT-BD registry is designed as a scalable infrastructure. In its initial phases, it will serve national research priorities; over time, it will expand to international collaborations, training opportunities, and joint projects. By combining phenotypic richness with state-of-the-art genomic technologies, the registry will contribute significantly to global efforts aimed at unraveling the biological basis of bipolar disorder.

Inclusion Criteria (Bipolar Disorder Cohort):

• Age 18-65 years.
• DSM-5 diagnosis of Bipolar I, II and NOS confirmed by SCID-5.
• Able to provide written informed consent.
• Willing to complete standardized phenotyping (e.g., YMRS, HDRS-17, FAST/WHODAS) and to provide biospecimens (minimum: whole blood in EDTA; optional: serum, plasma, PAXgene-RNA, cfDNA tubes).
• Stable psychotropic regimen for ≥14 days prior to sampling or drug-free for ≥14 days.

Inclusion Criteria (Control Cohort):

• Age 18-65 years.
• No lifetime DSM-5 psychiatric disorder (including bipolar and schizophrenia spectrum and others) by SCID-5.
• No first-degree family history of major psychiatric disorder (including bipolar and schizophrenia spectrum).
• Able to provide informed consent and blood samples for biobanking.
• No current psychotropic medication.

Exclusion Criteria (applies to both cohorts):

• Presence of neurological disorders (e.g., epilepsy, multiple sclerosis, Parkinson's disease).
• Severe, uncontrolled medical illness that could affect participation or biological measures (e.g., decompensated cardiac, renal, hepatic, or endocrine disease).
• Active infection or fever within 14 days; systemic corticosteroids or immunomodulators within 30 days; vaccination within 14 days.
• Blood transfusion within 3 months or blood donation within 2 weeks prior to sampling.
• Current substance use disorder.
• Pregnancy or breastfeeding at enrollment.
• Inability to comply with procedures or lack of capacity to consent (e.g., significant cognitive impairment, severe language barrier), or acute mania/psychosis requiring immediate hospitalization.

Participants will be recruited through the Department of Psychiatry at Selçuk University Medical Faculty in Konya, Türkiye, in collaboration with the Research and Treatment Society of Genetic Disorders (RTSGD) and the NeuroPsyBiT Consortium. The population includes adults aged 18-65 diagnosed with bipolar disorder who receive outpatient or inpatient psychiatric care at Selçuk University clinical facilities, as well as healthy control volunteers recruited from the local community and hospital staff. Both patient and control groups will contribute to the establishment of a national biobank and phenotypic data registry designed to support future genomic and epigenomic studies

De-identified (pseudonymised) IPD will be shared for verification/secondary/meta-research under controlled access, per FAIR+GDPR; minimal. Sociodemographics: age (bands), sex/gender, marital, education, SES/employment, region; gravidity/miscarriages; ethnicity where permitted. Clinical: onset age; prior psychiatric history; episode #/polarity; mixed/rapid-cycling/psychosis; hospitalisations; treatment history (dose/duration/levels); family history; suicidality; comorbidities; concomitant meds. Scales: HDRS/HAM-D, YMRS, ALDA, CGI, UKU, FAST, WHOQOL-BREF-TR, PSQI, MEQ-SF, MCTQ, CTQ-53, ASRS, SPS. Lifestyle: tobacco, alcohol, illicit, caffeine; sleep-wake regularity. Labs/biometrics: metabolic-syndrome, BMI, renal/liver, electrolytes, ESR/routine, HR, ECG; QRISK3 (derived score+timepoint only). Biospecimen metadata: type, timepoint, processing, storage, QC; no primary specimens or genomic raw data without approval. Docs: data dictionary/codebook, CRFs, scoring refs, derivation readme.

Individual Participant Data (IPD) and supporting documentation (Study Protocol, SAP, ICF, Analytic Code) will become available 12 months after study completion and will remain accessible for 5 years under controlled access agreements. After this period, renewal of access may be possible upon approval by the sponsor and the Turkish Health Ministry.

Only qualified researchers affiliated with recognized academic or clinical institutions may apply.

Requests must be accompanied by a formal research proposal, including clear objectives, methodology, and justification for data use.

All requests require Ethics Committee approval and explicit authorization from the Turkish Ministry of Health.

Data will be shared only in a de-identified, encrypted format via a secure on-premises or ministry-approved platform. No direct downloads or cloud transfer will be allowed.

Applicants must sign a Data Use Agreement (DUA), prohibiting re-identification attempts, redistribution, or secondary use beyond the approved proposal.

Publication of analyses derived from the IPD will require pre-review by the sponsor consortium (RTSGD/NeuroPsyBiT) to ensure compliance with ethical, legal, and scientific standards.

Violations of these criteria will result in immediate termination of access and legal consequences under Turkish data protection laws (KVKK) an