Cortical Thickness and Clinical Profile in Never Medicated Individuals with Psychosis

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Abstract Submission 

Luis Rivera-Chavez¹, Triana Tello-Gerez¹, Matthew Danyluik², Pablo Leon-Ortiz¹, Yohan Yee², Francisco Reyes-Madrigal¹, Mallar Chakravarty², Camilo de la Fuente-Sandoval¹

¹Laboratory of Experimental Psychiatry, National Institute of Neurology and Neurosurgery, Mexico City, Mexico, ²Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montreal, Quebec

Luis Rivera-Chavez, MD, MSc.  
Laboratory of Experimental Psychiatry, National Institute of Neurology and Neurosurgery
Mexico City, Mexico

Triana Tello-Gerez, MD  
Laboratory of Experimental Psychiatry, National Institute of Neurology and Neurosurgery
Mexico City, Mexico

Matthew Danyluik, PhD Student  
Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University
Montreal, Quebec

Pablo Leon-Ortiz, MD, PhD  
Laboratory of Experimental Psychiatry, National Institute of Neurology and Neurosurgery
Mexico City, Mexico

Yohan Yee  
Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University
Montreal, Quebec

Francisco Reyes-Madrigal, MD, MSc  
Laboratory of Experimental Psychiatry, National Institute of Neurology and Neurosurgery
Mexico City, Mexico

Mallar Chakravarty, PhD  
Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University
Montreal, Quebec

Camilo de la Fuente-Sandoval  
Laboratory of Experimental Psychiatry, National Institute of Neurology and Neurosurgery
Mexico City, Mexico

Reduced cortical thickness (CT) is well documented in schizophrenia and has been reported to progress throughout the course of illness. While previously established that a longer duration of untreated psychosis (DUP) is a predictor of poor clinical outcome, the field still lacks information on structural brain abnormalities in medication naive subjects with particular long DUP. In the present study we present a unique sample of never medicated first episode of psychosis patients (FEP) with a wide range of DUP.

FEP patients that had never been medicated with antipsychotics, along with healthy controls, were recruited at the National Institute of Neurology and Neurosurgery of Mexico. Clinical evaluation at recruitment included the MATRICS Consensus Cognitive Battery (MCCB). Magnetic resonance studies were performed on two scanners: some participants were scanned in a 3T GE whole-body scanner (Signa Excite HDxt) with a high-resolution 8-channel head coil, using a T1-weighted spoiled gradient-echo 3-dimensional axial acquisition (SPGR, echo time [TE] = 5.7ms, repetition time [TR] = 13.4ms, inversion time [IT] = 450ms, flip angle = 20°, field of view [FOV] = 25.6cm, ≥256 × ≥256 matrix, slice thickness ≤ 1.2mm), oriented above and parallel to the anterior-posterior commissure line. The other participants were scanned on a 3 T Siemens scanner (Magnetom Skyra), using a 20-channel phased array transmit/receive-head coil, using a high-resolution T1-weighted three-dimensional magnetization-prepared rapid acquisition with gradient echo (MPRAGE; TE = 5 ms, TR = 12 ms, IT = 450 ms, flip angle = 20⁰, FOV = 25.6 cm, 256x256 matrix, 186 slices, slice thickness = 1 mm), oriented above and parallel to the anterior commissure-posterior commissure line. T1-weighted images were preprocessed with bpipe pipeline (http://github.com/CobraLab/minc-bpipe-library/), which includes bias field correction, neck cropping, and Brain Extraction based on nonlocal Segmentation Technique (BEaST). CT analysis was done with CIVET processing pipeline (version 2.1.1; Montreal Neurological Institute). To remove unwanted scan variability due to scanner, CovBat harmonization was performed on data before analysis. To compare CT measures between groups, vertex-wise CT diagnosis contrast analyses were conducted, while accounting for age and sex in a linear model. For spatial distribution visualization, t-values were projected into a brain map of the participants' average surface with false discovery rates (FDR) thresholds set at 5-10%. Means of CT were used in linear models to compare groups and explore for possible correlations with demographic and clinical variables.

Fifty-six FEP patients (DUP mean[range] in weeks = 145.79[1-1300]) and 52 healthy controls completed all clinical evaluations and MRI scanning (GE scanner n=47, Siemens scanner n=61). Obtained CT mean was lower in FEP than in controls (t=2.56, df=93, p=0.01). Regions with most differences in CT were found at the right and left occipital lobe, postcentral gyrus of the left parietal lobe, superior gyrus of the left temporal lobe, and the right uncus (Figure). The linear model obtained with mean CT confirmed a group effect, besides an effect due to age and sex (groupFEP t-value=-2.468, p=0.01; age t-value=-5.63, p<0.01; sexmale t-value=2.41, p=0.02). No significant associations were found in linear models of mean CT with cognitive domains values in either group. However, trends were observed for social cognition in the control group (t-value=1.92, p=0.06).

Present findings are in line with previous studies reporting decreased CT in patients with psychosis compared to controls. Dissimilar to published results on the matter, differences localized to the frontal lobe were not found. This could potentially be explained by the variability induced by the uncommonly prolonged DUP of the never medicated FEP group. Further studies are necessary to corroborate and expand findings in individuals with long DUP.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Reasoning and Problem Solving

Working Memory

Image Registration and Computational Anatomy ²

Cortical Anatomy and Brain Mapping

Cognition

Cortex

MRI

Psychiatric Disorders

Schizophrenia