Neuroanatomical Markers Of Persistence Versus Remission Of Adhd

The identification of neurobiological markers associated with childhood status and persistence vs. remission ofthe attention deficit/hyperactivity disorder (ADHD) over development, and the translation of these markers intomore effective diagnosis and intervention strategies are major priorities of NIMH. The persistence of ADHD intoadulthood in many but not all afflicted children attests to the considerable variability in the remission ofsymptoms over development. However, evidence of cortical and subcortical structural anomalies associatedwith the persistence versus remission of ADHD is relatively limited, and not fully consistent. [Our group is in aunique position to test the neurobiological mechanisms associated with the childhood status and thedevelopmental trajectories of ADHD]. We recently completed a 15-year longitudinal study of ADHD thatrecruited and clinically followed a large sample of children with ADHD into adulthood, as well as a well-matched sample of never ADHD controls that was recruited in adolescence and followed into adulthood. Thislarge sample represents the diversity of outcomes characteristic of ADHD and was scanned with multi-modalneuroimaging in adulthood. Published results of our functional neuroimaging study support the distinction inneural mechanisms associated with the emergence and remission of ADHD. Youngadults diagnosed withADHD in childhood were marked by reducedregardless of adult outcome, while the remission of ADHD symptoms in adulthood was associatedwith enhanced cue-related thalamo-prefrontal functional connectivity. [However, the neuroanatomical evidenceof this double-dissociation model of ADHD emergence and remission has not yet been investigatedcue-related thalamus activation and functional connectivity withbrainstem.By capitalizing on the availability of both neuroimaging and longitudinal clinical data from our recentlycompleted study and utilizing advanced neuroimaging analysis and multivariate machine leaning techniques,this proposal aims to identify the neuroanatomical correlates of childhood status and remission of ADHD inyoung adults, and to link the anatomical evidence with the functional and longitudinal clinical evidenceassociated with persistent vs. remitted ADHD. The ultimate goal is to translate hypothesis-drivenneuroanatomical correlates of adult outcome into clinically applicable biomarkers that can guide individualizedinterventions in youth with ADHD.] Our central hypotheses are that: (1) childhood ADHD is associated withthalamo-brainstem structural disconnectivity that endures into adulthood regardless of the developmentaltrajectory of the disorder; and (2) diminution of symptoms is related to optimal prefrontal development and itsanatomical connectivity with other brain regions. The ultimate goal of this proposal is innovative and directlyrelevant to the NIMH mission, to translate hypothesis-driven neuroanatomical correlates of adult outcome intomore clinically applicable biomarkers that can serve as targets for the development of interventions in youthwith ADHD.