T88. THE IMPACT OF AGE OF ONSET AND ILLNESS DURATION ON WHITE MATTER AND COGNITION TRAJECTORIES IN SCHIZOPHRENIA: A 7-YEAR FOLLOW-UP STUDY ACROSS MULTIPLE TIME-POINTS. (9th April 2019)

• Record Type: Journal Article
• Authors: Jensen, Marie B; Ebdrup, Bjørn H; Pantelis, Christos; Nielsen, Mette Ø; Raghava, Jayachandra Mitta; Rostrup, Egill; Bojesen, Kirsten; Glenthøj, Birte Y; Mandl, Rene C W; Fagerlund, Birgitte
• Is Part Of: Schizophrenia bulletin. Volume 45(2019)Supplement 2
• Page Start: S237
• Page End: S238
• Publication Date: 2019-04-09
• Subjects: Schizophrenia -- Periodicals; Schizophrenia -- Research -- Periodicals; 616.898005
• DOI: 10.1093/schbul/sbz019.368
• Languages: English
• ISSNs: 0586-7614

Abstract

Abstract: Background: Schizophrenia is characterized by cognitive deficits persisting throughout the illness from the first episode. These deficits may be associated with disruptions in white matter (WM) connectivity. Steeper age-related reductions in WM have been found in schizophrenia patients compared to healthy controls (HC), but it is unclear if these reductions are mainly influenced by age of illness onset, duration of illness, or an interaction between the two. Previous longitudinal studies of WM microstructure (measured with fractional anisotropy) have predominantly investigated medicated patients at two time-points and follow-up periods are generally limited to months. We aim to examine the impact of age at inclusion (in patients defined as illness onset) and time since inclusion (in patients defined as illness duration) on white matter and cognition trajectories in schizophrenia compared to healthy controls. Methods: We included 119 antipsychotic-naïve first-episode patients with an ICD-10 diagnosis of schizophrenia (mean age: 24, 2 [18, 2-42, 6], 55 % men) and 111 matched HC (mean age: 24, 2 [18, 1-42, 9], 54 % men) in a prospective longitudinal follow-up study. Patients and HC had completed between one and six visits with valid MRI and/or cognitive data. This resulted in a total of 791 visits (at inclusion, 6 weeks, 6 months, 1 year, 2 years, and 5–7 years). Subjects were scanned on a Philips 3T MRI scanner with a diffusion weighted sequence and examined with the Brief Assessment of Cognition in Schizophrenia (BACS). Outcome measures were mean fractional anisotropy (FA) and two cognitive measures: word fluency and processing speed. Using linear mixed models, we analyzed main effects and interaction effects of group, age at inclusion (age), time since inclusion (time), and time since inclusion squared (time^2) for FA, fluency, and processing speed, respectively. Results: For processing speed, we found a main effect of group (p<.001), time^2 (p<.001) and age (p=.002) and an interaction between group*age*time (p=.01). For fluency, we found a main effect of group (p<.001) and an interaction between group*time^2 (p=.02). Fluency also showed a trend level interaction effect of group*age*time^2 (p=0.06). For FA, we found a trend level main effect of time^2 (p=.07) and a trend level significance for the interaction between group*age*time (p=.07). Discussion: Our analyses showed significant group differences on both processing speed and fluency, a significant time effect on processing speed and a trend level effect of time on FA. There were differential quadratic changes over time between the groups on fluency, with a trend level interaction with age at inclusion (illness onset for patients). Age at inclusion had a significantly different impact over time between patients and HC on processing speed. A similar, trend level interaction between age, time and group was shown on FA. These preliminary results suggest differential trajectories for schizophrenia patients and HC on processing speed, fluency and FA, dependent on the age at inclusion.