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T154. WHITE MATTER INTEGRITY, DURATION OF UNTREATED PSYCHOSIS, AND ANTIPSYCHOTIC TREATMENT RESPONSE IN MEDICATION-NAïVE FIRST EPISODE PSYCHOSIS PATIENTS
BACKGROUND: It is becoming increasingly clear that longer duration of untreated psychosis (DUP) is associated with adverse clinical outcomes in patients with psychosis spectrum disorders. Especially because this association is often cited when justifying early intervention efforts, it is imperative...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234356/ http://dx.doi.org/10.1093/schbul/sbaa029.714 |
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author | Kraguljac, Nina Thomas, Anthony Morgan, Charity Jindal, Ripu Lahti, Adrienne |
author_facet | Kraguljac, Nina Thomas, Anthony Morgan, Charity Jindal, Ripu Lahti, Adrienne |
author_sort | Kraguljac, Nina |
collection | PubMed |
description | BACKGROUND: It is becoming increasingly clear that longer duration of untreated psychosis (DUP) is associated with adverse clinical outcomes in patients with psychosis spectrum disorders. Especially because this association is often cited when justifying early intervention efforts, it is imperative to better understand underlying biological mechanisms. METHODS: We recruited 74 antipsychotic-naïve first episode psychosis (FEP) patients and 45 matched healthy controls in this trial. At baseline, we used a human connectome style diffusion weighted imaging (DWI) sequence to quantify white matter integrity in both groups. Patients then received 16 weeks of treatment with risperidone. DWI scans were acquired with opposite phase encoding directions [TR/TE: 3230ms/ 89.20ms; multiband acceleration factor 4, Flip angle: 84°; slice thickness 1.5mm, 92 slices, voxel size 1.5mm3, 92 diffusion weighted images distributed equally over 2 shells with b-values of ~ 1500s/mm2 and ~ 3000s/mm2, as well as 7 interspersed b= ~ 0s/mm2 images]). Preprocessing of DWI images was performed in TORTOISE (version 3.1.2). This included correction for thermal noise, Gibbs-ringing, high b-value based bulk motion and eddy-current distortions using a MAP-MRI model, resampling of images to 1mm3, and rotation of gradient tables independently for each DWI phase encoding direction. Then, DR-BUDDI was used to correct EPI distortions with input from the anatomical image and to combine the two datasets using geometric averaging to generate the final corrected dataset. Tensors were computed with DIFF_CALC using a linear fitting algorithm. To spatially normalize images to the Illinois Institute of Technology atlas (IIT4) space, we implemented an optimized non-linear image registration procedure using a modified version of 3dQwarp in AFNI. We compared whole brain fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD) and radial diffusivity between groups. To test if structural white matter integrity mediates the relationship between longer DUP and poorer treatment response, we fit a mediator model and estimated indirect effects. RESULTS: Groups did not differ in age (FEP: 23.83+/-6.21 years; HC: 24.78+/-6.24 years), sex (FEP: 65.2% male; HC: 64.4% male), or parental socioeconomic status (FEP: 5.95+/-4.83; HC: 4.22+/-4.06). We found decreased whole brain FA and AD in medication-naive FEP compared to controls. In patients, lower FA was correlated with longer DUP (r= -0.32; p= 0.03) and poorer subsequent response to antipsychotic treatment (r= 0.40; p= 0.01). Importantly, we found a significant mediation effect for FA (indirect effect: -2.70; p= 0.03), indicating that DUP exerts its effects on treatment response through affecting white matter integrity. DISCUSSION: To our knowledge, this is the first study to examine a putative role of white matter integrity in the observed association between DUP and clinical outcomes in first episode psychosis. Our data provide empirical support to the idea the DUP may have fundamental pathogenic effects on the natural history of psychosis, suggest a biological mechanism underlying this phenomenon, and underscore the importance of early intervention efforts in this disabling neuropsychiatric syndrome. |
format | Online Article Text |
id | pubmed-7234356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72343562020-05-23 T154. WHITE MATTER INTEGRITY, DURATION OF UNTREATED PSYCHOSIS, AND ANTIPSYCHOTIC TREATMENT RESPONSE IN MEDICATION-NAïVE FIRST EPISODE PSYCHOSIS PATIENTS Kraguljac, Nina Thomas, Anthony Morgan, Charity Jindal, Ripu Lahti, Adrienne Schizophr Bull Poster Session III BACKGROUND: It is becoming increasingly clear that longer duration of untreated psychosis (DUP) is associated with adverse clinical outcomes in patients with psychosis spectrum disorders. Especially because this association is often cited when justifying early intervention efforts, it is imperative to better understand underlying biological mechanisms. METHODS: We recruited 74 antipsychotic-naïve first episode psychosis (FEP) patients and 45 matched healthy controls in this trial. At baseline, we used a human connectome style diffusion weighted imaging (DWI) sequence to quantify white matter integrity in both groups. Patients then received 16 weeks of treatment with risperidone. DWI scans were acquired with opposite phase encoding directions [TR/TE: 3230ms/ 89.20ms; multiband acceleration factor 4, Flip angle: 84°; slice thickness 1.5mm, 92 slices, voxel size 1.5mm3, 92 diffusion weighted images distributed equally over 2 shells with b-values of ~ 1500s/mm2 and ~ 3000s/mm2, as well as 7 interspersed b= ~ 0s/mm2 images]). Preprocessing of DWI images was performed in TORTOISE (version 3.1.2). This included correction for thermal noise, Gibbs-ringing, high b-value based bulk motion and eddy-current distortions using a MAP-MRI model, resampling of images to 1mm3, and rotation of gradient tables independently for each DWI phase encoding direction. Then, DR-BUDDI was used to correct EPI distortions with input from the anatomical image and to combine the two datasets using geometric averaging to generate the final corrected dataset. Tensors were computed with DIFF_CALC using a linear fitting algorithm. To spatially normalize images to the Illinois Institute of Technology atlas (IIT4) space, we implemented an optimized non-linear image registration procedure using a modified version of 3dQwarp in AFNI. We compared whole brain fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD) and radial diffusivity between groups. To test if structural white matter integrity mediates the relationship between longer DUP and poorer treatment response, we fit a mediator model and estimated indirect effects. RESULTS: Groups did not differ in age (FEP: 23.83+/-6.21 years; HC: 24.78+/-6.24 years), sex (FEP: 65.2% male; HC: 64.4% male), or parental socioeconomic status (FEP: 5.95+/-4.83; HC: 4.22+/-4.06). We found decreased whole brain FA and AD in medication-naive FEP compared to controls. In patients, lower FA was correlated with longer DUP (r= -0.32; p= 0.03) and poorer subsequent response to antipsychotic treatment (r= 0.40; p= 0.01). Importantly, we found a significant mediation effect for FA (indirect effect: -2.70; p= 0.03), indicating that DUP exerts its effects on treatment response through affecting white matter integrity. DISCUSSION: To our knowledge, this is the first study to examine a putative role of white matter integrity in the observed association between DUP and clinical outcomes in first episode psychosis. Our data provide empirical support to the idea the DUP may have fundamental pathogenic effects on the natural history of psychosis, suggest a biological mechanism underlying this phenomenon, and underscore the importance of early intervention efforts in this disabling neuropsychiatric syndrome. Oxford University Press 2020-05 2020-05-18 /pmc/articles/PMC7234356/ http://dx.doi.org/10.1093/schbul/sbaa029.714 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Poster Session III Kraguljac, Nina Thomas, Anthony Morgan, Charity Jindal, Ripu Lahti, Adrienne T154. WHITE MATTER INTEGRITY, DURATION OF UNTREATED PSYCHOSIS, AND ANTIPSYCHOTIC TREATMENT RESPONSE IN MEDICATION-NAïVE FIRST EPISODE PSYCHOSIS PATIENTS |
title | T154. WHITE MATTER INTEGRITY, DURATION OF UNTREATED PSYCHOSIS, AND ANTIPSYCHOTIC TREATMENT RESPONSE IN MEDICATION-NAïVE FIRST EPISODE PSYCHOSIS PATIENTS |
title_full | T154. WHITE MATTER INTEGRITY, DURATION OF UNTREATED PSYCHOSIS, AND ANTIPSYCHOTIC TREATMENT RESPONSE IN MEDICATION-NAïVE FIRST EPISODE PSYCHOSIS PATIENTS |
title_fullStr | T154. WHITE MATTER INTEGRITY, DURATION OF UNTREATED PSYCHOSIS, AND ANTIPSYCHOTIC TREATMENT RESPONSE IN MEDICATION-NAïVE FIRST EPISODE PSYCHOSIS PATIENTS |
title_full_unstemmed | T154. WHITE MATTER INTEGRITY, DURATION OF UNTREATED PSYCHOSIS, AND ANTIPSYCHOTIC TREATMENT RESPONSE IN MEDICATION-NAïVE FIRST EPISODE PSYCHOSIS PATIENTS |
title_short | T154. WHITE MATTER INTEGRITY, DURATION OF UNTREATED PSYCHOSIS, AND ANTIPSYCHOTIC TREATMENT RESPONSE IN MEDICATION-NAïVE FIRST EPISODE PSYCHOSIS PATIENTS |
title_sort | t154. white matter integrity, duration of untreated psychosis, and antipsychotic treatment response in medication-naïve first episode psychosis patients |
topic | Poster Session III |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234356/ http://dx.doi.org/10.1093/schbul/sbaa029.714 |
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