| 001 | 1044452 | ||
| 005 | 20250723202239.0 | ||
| 024 | 7 | _ | |a 10.34734/FZJ-2025-03206 |2 datacite_doi |
| 037 | _ | _ | |a FZJ-2025-03206 |
| 100 | 1 | _ | |a Hettwer, Meike |0 P:(DE-Juel1)187157 |b 0 |e Corresponding author |u fzj |
| 245 | _ | _ | |a Mapping Cortical Alteration Patterns in Transdiagnostic Psychopathology: A Systems Framework IntegratingCortical Architecture and Developmental Susceptibility |f - 2025-07-21 |
| 260 | _ | _ | |c 2024 |
| 300 | _ | _ | |a 127 |
| 336 | 7 | _ | |a Output Types/Dissertation |2 DataCite |
| 336 | 7 | _ | |a DISSERTATION |2 ORCID |
| 336 | 7 | _ | |a PHDTHESIS |2 BibTeX |
| 336 | 7 | _ | |a Thesis |0 2 |2 EndNote |
| 336 | 7 | _ | |a Dissertation / PhD Thesis |b phd |m phd |0 PUB:(DE-HGF)11 |s 1753258810_10103 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a doctoralThesis |2 DRIVER |
| 502 | _ | _ | |a Dissertation, HHU Düsseldorf, 2024 |c HHU Düsseldorf |b Dissertation |d 2024 |o 2025-07-21 |
| 520 | _ | _ | |a Transdiagnostic research in psychiatry indicates substantial commonalities between mental disorders.The high prevalence of psychiatric comorbidity has been attributed to shared etiologies and overlappingalterations in brain structure and function. Yet, it remains unclear whether overlapping brain alterationsarise from shared constraints imposed by underlying neurobiology. This thesis provides insights intohow brain organization, particularly the spatial architecture and developmental trajectories of the cortex,may constrain transdiagnostic cortical alterations and susceptibility during vulnerable developmentalperiods.A population-level model aimed to uncover systematically co-occurring cortical thickness (CT)alterations across six mental disorders (Study 1). Identified transdiagnostic co-alterations reflectedelements of underlying connectome organization, particularly lateral prefrontal and medial-temporalconnectivity profiles. Moreover, they were spatially organized, with prefrontal vs. temporal and sensorylimbicvs. occipitoparietal regions exhibiting distinct co-alteration profiles. Overall, the extent to whichany two regions exhibited similar CT alterations across disorders reflected their similarity incytoarchitecture, gene expression profile, and functional task engagement. Study 1 thus provides insightsinto the spatial organization of transdiagnostic CT alterations and how the cortex’s heterogeneousneurobiology may guide these recurrent patterns.A longitudinal neurodevelopmental model was applied in adolescents and young adults to studysusceptibility in a period during which first psychiatric symptoms often emerge (Study 2). The modelinvestigated how variation in mental well-being in response to psychosocial adversity relates to ongoingcortical maturation, particularly focusing on the asynchronous progression of plasticity andconsolidation. Nuanced intracortical myelin mapping revealed that a higher rate of anterolateralprefrontal myelination and widespread association cortex reorganization were associated with positivechanges in adolescents’ resilience to psychosocial adversity. Conversely, increasing susceptibility wasrelated to weaker myeloarchitectonic consolidation and decreased stability of prefrontal functionalnetworks. Study 2 thus revealed that the efficacy with which adolescents navigate psychosocialchallenges varies in relation to ongoing cortical refinement processes at multiple scales.The current work advances our understanding of how the cortex’s spatial and developmentalarchitecture shapes the systematic organization of transdiagnostic cortical alterations. As such, corticalalterations relevant to dimensional psychopathology may be embedded in an intrinsic cortical coordinatesystem defined by multiple axes of neurobiological heterogeneity and protracted development. Furtherresearch is needed to understand potentially synchronized spatiotemporal progressions along observedco-alteration patterns. Moreover, findings can inspire neurodevelopmentally informed interventionstailored to the timing of plastic periods of brain circuits involved in navigating psychosocial challenges. |
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