Neurological Soft Signs Predict Abnormal Cerebellar-thalamic Tract Development and Negative Symptoms in Adolescents at High Risk for Psychosis: a Longitudinal Perspective

Overview

Journal Schizophr Bull

Publisher Oxford University Press

Specialty Psychiatry

Date 2013 Dec 31

PMID 24375457

Citations 62

Authors

Vijay A Mittal

Derek J Dean

Jessica A Bernard

Joseph M Orr

Andrea Pelletier-Baldelli

Emily E Carol

Tina Gupta

Jessica Turner

Daniel R Leopold

Briana L Robustelli

Zachary B Millman

Affiliations

Soon will be listed here.

Abstract

Introduction: 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.

Discussion: 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.

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