Does early-life stress promote protracted neuroinflammation in adults? Towards understanding early developmental origins of accelerated brain ageing

• Conditions: euroinflammation, Brainaging; Z61; Problems related to negative life events in childhood

• Registration Number: DRKS00023288
• Lead Sponsor: Institut für Medizinische Psychologie der Charité - Universitätsmedizin Berlin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-10-30
• Study Completion: 2023-12-31
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 364

Inclusion Criteria

Ability to give consent
- Legally effective, written declaration of consent to participate in the study
- Existing health insurance to clarify possible random findings, Additional inclusion criteria ELS-group
- ELS from childhood until menarche onset, recorded by a standardized questionnaire and interview

Exclusion Criteria

- Women/men with somatic, psychiatric or neurological diseases or treatments that may impair cognitive functions or are unstable under drug treatment (e.g. thyroid diseases, hypertension, hyperlipidemia) and may influence the parameters to be investigated
- Structural MRI abnormalities that may be associated with cognitive deficits, such as focal lesions (cortical infarction, subdural hematoma, intracerebral hemorrhage or brain tumor) and severe leukoencephalopathies (assessed by Scheltens score)
- Use of psychotropic substances (except medication such as antidepressants, neuroleptics) in the last 3 months
- Antidemential therapy in the last 3 months (e.g. acetylcholine esterase inhibitors, NMDA antagonists)
- current manifest psychiatric disease of axis I disorders according to ICD-10 or DSM-V: addiction disorders (except nicotine), bipolar disorder, schizophrenic disorder, organic mental disorders. Depression, anxiety disorders or post-traumatic stress disorders are not exclusion criteria.
- current cancer
- past immunosuppressive therapy within the last 3 months (e.g. glucocorticoids, cytostatics, antibody therapy, TNF-alpha-blockers, calcineurin inhibitors, TOR inhibitors, interferon therapy)
- MRI contraindications (e.g. pacemakers, metallic or electronic implants, metallic splinters, surgical clamps)
- Medicine or drug abuse
- Claustrophobia
- Pregnancy (recorded via questionnaires on contraindications for MRT examinations)
- Sensorineural hearing loss above 30dB and tinnitus
- Insufficient knowledge of the German language
Additional exclusion criteria control group
- ELS recorded by a standardized questionnaire and an interview

Study & Design

• Study Type: observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Markers for neuroinflammation are measured by quantitative multiparameter mapping (MPM); MPM measures microstructural changes such as myelin, iron content and macrophage activity<br>2. Determination of the calculated brain age using multimodal MRI data to analyze a brain age score including functional and structural connectivity, cortical thickness, cortical surface and subcortical volume in relation to chronological age<br>

Secondary Outcome Measures

Name	Time	Method
- Neurocognitive functions are determined using standardized neuropsychological testing procedures for cognitive performance<br>- Quantification of brain metabolites [including NAA, myoinositol, choline, creatine and glutamate using single-voxel 1H-MR spectroscopy in the hippocampus and cinguli posterior gyrus<br>- Determination of systemic inflammation and senescence markers in venous blood (e.g. IL-6, CRP, TNF-alpha, lymphocyte immunophenotyping, telomer length, mitogenically stimulated telomerase activity, P16INK4a). Additional determination of risk markers in venous blood for neurodegenerative diseases (e.g. Aß40, Aß42, neurofilament light protein)<br>- Standard rating scales will be used to assess depression as a moderator, e.g. Beck Depression Inventory (BDI-II; Hautzinger et al., 2009)