title: Neurological soft signs predict abnormal cerebellar-thalamic tract development and negative symptoms in adolescents at high risk for psychosis: a longitudinal perspective.
abstract: BACKGROUND
  There is an emerging consensus that neurological soft signs (NSS) may not be "soft" at all but rather may reflect neuropathy, particularly in the cerebellum and thalamus. However, our understanding of connective tract abnormalities is limited, and to date, there have been no investigations examining NSS and longitudinal white matter development during the prodrome. Mapping the correlates of NSS in ultrahigh-risk (UHR) youth offers potential for highlighting a viable biomarker as well as for advancing understanding of pathogenic processes during the adolescent risk period.
  
  
  METHODS
  A total of 68 (33 UHR and 35 healthy control) adolescents were assessed with an NSS inventory, structured interviews, and diffusion tensor imaging. Fractional anisotropy (FA) of theoretically relevant cerebellar-thalamic tracts was calculated (left/right superior cerebellar peduncles [SCPs]). Twelve months later, a subset of 30 (15 UHR and 15 control) participants returned for follow-up diffusion tension imaging/clinical assessments.
  
  
  RESULTS
  UHR youth exhibited elevated NSS across domains. While there were no group differences in the integrity of the SCPs at baseline, controls showed a normative increase while the UHR group showed a decrease in FA over 12 months. NSS predicted a longitudinal decrease in cerebellar-thalamic FA and elevations in negative but not positive symptoms 12 months later.
  
  
  CONCLUSIONS
  Findings of abnormal white matter development provide direct empirical evidence to support prominent neurodevelopmental theories. The predictive relationships between NSS and longitudinal cerebellar-thalamic tract integrity and negative symptom course provide insight into the role of cognitive dysmetria in the high-risk period and inform on a unique biomarker tied to core features underlying psychosis.
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO; Center for Neuroscience, University of Colorado Boulder, Boulder, CO; vijay.mittal@colorado.edu.
authors.forename: Vijay A
authors.initials: VA
authors.lastname: Mittal
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO; Center for Neuroscience, University of Colorado Boulder, Boulder, CO;
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Dean
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO;
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Bernard
authors.affiliation: Institute for Cognitive Science, University of Colorado Boulder, Boulder, CO;
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Orr
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO; Center for Neuroscience, University of Colorado Boulder, Boulder, CO;
authors.forename: Andrea
authors.initials: A
authors.lastname: Pelletier-Baldelli
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO;
authors.forename: Emily E
authors.initials: EE
authors.lastname: Carol
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO;
authors.forename: Tina
authors.initials: T
authors.lastname: Gupta
authors.affiliation: Department of Psychology, Georgia State University, Atlanta, GA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Turner
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO; Center for Neuroscience, University of Colorado Boulder, Boulder, CO;
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Leopold
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO;
authors.forename: Briana L
authors.initials: BL
authors.lastname: Robustelli
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO;
authors.forename: Zachary B
authors.initials: ZB
authors.lastname: Millman
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D015415:Biomarkers; D002531:Cerebellum / Q000254:growth & development / Q000473:pathology; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009422:Nervous System Diseases / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000254:growth & development / Q000473:pathology; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000473:pathology / Q000503:physiopathology; D012306:Risk; D013788:Thalamus / Q000254:growth & development / Q000473:pathology; D066127:White Matter / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: DTI; UHR; cognitive dysmetria; neurological soft signs; prodrome; psychosis; superior cerebellar peduncle