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@PHDTHESIS{Hettwer:1044452,
      author       = {Hettwer, Meike},
      title        = {{M}apping {C}ortical {A}lteration {P}atterns in
                      {T}ransdiagnostic {P}sychopathology: {A} {S}ystems
                      {F}ramework {I}ntegrating{C}ortical {A}rchitecture and
                      {D}evelopmental {S}usceptibility},
      school       = {HHU Düsseldorf},
      type         = {Dissertation},
      reportid     = {FZJ-2025-03206},
      pages        = {127},
      year         = {2024},
      note         = {Dissertation, HHU Düsseldorf, 2024},
      abstract     = {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.},
      cin          = {INM-7},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {5252 - Brain Dysfunction and Plasticity (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5252},
      typ          = {PUB:(DE-HGF)11},
      doi          = {10.34734/FZJ-2025-03206},
      url          = {https://juser.fz-juelich.de/record/1044452},
}