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| Dissertation / PhD Thesis | FZJ-2025-01575 |
2024
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Please use a persistent id in citations: doi:10.34734/FZJ-2025-01575
Abstract: To date, early recognition and diagnosis of many neuropsychiatric diseases remainschallenging, resulting in frequent under- or misdiagnosis. To reduce the suffering ofpatients and to lower the economic burden, neuropsychiatric research began to focus onbiomarker development in the last two decades. While biomarkers can serve differentpurposes and can be derived from a variety of modalities, this thesis evaluates thecurrent state of biomarker development for chronic and non-chronic neuropsychiatricdiseases at the examples of behavioral variant frontotemporal dementia (bvFTD),postpartum depression (PPD), and adjustment disorder (AjD) in the postpartum period.More specifically, the predictive value of socio-demographic and clinical-anamnesticinformation in addition to remote mood and stress assessments was evaluated (study 1),and early structural and functional brain alterations (study 2) were examined in PPD andAjD. Moreover, spatial correlations of structural and functional neuroimaging withneurotransmitter density were evaluated as neurotransmitter vulnerability biomarker inbvFTD (study 3).While the first study demonstrated that PPD, AjD, and healthy controls can be accuratelydifferentiated using remote mood assessments and clinical-amnestic information (i.e.,postnatal depression and attachment scores), the second study revealed no robust earlystructural and functional brain alterations in PPD and AjD. The third study showed thatreduced functional connectivity in frontotemporal and frontoparietal regions in patientswith bvFTD co-localized with the distribution of receptors and transporters of ´-aminobutyric acid-ergic, norepinephrinergic, and serotonergic neurotransmitter systems,and their encoding mRNA gene expression, indicating a specific neurotransmittervulnerability in patients with bvFTD.In summary, the first two studies demonstrated the value of utilizing remote assessmentsin combination with machine learning for early recognition of PPD and AjD. Moreover,the third study demonstrated the potential of spatial correlations of brain structure andfunction with neurotransmitter density to assess neurotransmitter vulnerability. In thefuture, these biomarker development approaches may also prove useful for the earlyrecognition and diagnosis of other neuropsychiatric diseases.
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