White matter changes in psychosis risk relate to development and are not impacted by the transition to psychosis.

Subtle alterations in white matter microstructure are observed in youth at clinical high risk (CHR) for psychosis. However, the timing of these changes and their relationships to the emergence of psychosis remain unclear. Here, we track the evolution of white matter abnormalities in a large, longitudinal cohort of CHR individuals comprising the North American Prodrome Longitudinal Study (NAPLS-3). Multi-shell diffusion magnetic resonance imaging data were collected across multiple timepoints (1-5 over 1 year) in 286 subjects (aged 12-32 years): 25 CHR individuals who transitioned to psychosis (CHR-P; 61 scans), 205 CHR subjects with unknown transition outcome after the 1-year follow-up period (CHR-U; 596 scans), and 56 healthy controls (195 scans). Linear mixed effects models were fitted to infer the impact of age and illness-onset on variation in the fractional anisotropy of cellular tissue (FAT) and the volume fraction of extracellular free water (FW). Baseline measures of white matter microstructure did not differentiate between HC, CHR-U and CHR-P individuals. However, age trajectories differed between the three groups in line with a developmental effect: CHR-P and CHR-U groups displayed higher FAT in adolescence, and 4% lower FAT by 30 years of age compared to controls. Furthermore, older CHR-P subjects (20+ years) displayed 4% higher FW in the forceps major (p < 0.05). Prospective analysis in CHR-P did not reveal a significant impact of illness onset on regional FAT or FW, suggesting that transition to psychosis is not marked by dramatic change in white matter microstructure. Instead, clinical high risk for psychosis-regardless of transition outcome-is characterized by subtle age-related white matter changes that occur in tandem with development.

An Introduction to the Human Connectome Project for Early Psychosis.

BACKGROUND: The time following a recent onset of psychosis is a critical period during which intervention may be maximally effective. Studying individuals in this period also offers an opportunity to investigate putative brain biomarkers of illness prior to the long-term effects of chronicity and medication. The Human Connectome Project for Early Psychosis (HCP-EP) was funded by the National Institutes of Mental Health (NIMH) as an extension of the original Human Connectome Project's approach to understanding the human brain and its structural and functional connections. DESIGN: The HCP-EP data were collected at 3 sites in Massachusetts (Beth Israel Deaconess Medical Center, McLean Hospital, and Massachusetts General Hospital), and one site in Indiana (Indiana University). Brigham and Women's Hospital served as the data coordination center and as an imaging site. RESULTS: The HCP-EP dataset includes high-quality clinical, cognitive, functional, neuroimaging, and blood specimen data acquired from 303 individuals between the ages of 16-35 years old with affective psychosis (n = 75), non-affective psychosis (n = 148), and healthy controls (n = 80). Participants with early psychosis were within 5 years of illness onset (mean duration = 1.9 years, standard deviation = 1.4 years). All data and novel or modified analytic tools developed as part of the study are publicly available to the research community through the NIMH Data Archive (NDA) or GitHub (https://github.com/pnlbwh). CONCLUSIONS: This paper provides an overview of the specific HCP-EP procedures, assessments, and protocols, as well as a brief characterization of the study participants to make it easier for researchers to use this rich dataset. Although we focus here on discussing and comparing affective and non-affective psychosis groups, the HCP-EP dataset also provides sufficient information for investigators to group participants differently.