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Microstructural white-matter abnormalities associated with treatment resistance, severity and duration of illness in major depression

Published online by Cambridge University Press:  21 August 2013

J. de Diego-Adeliño ,
P. Pires ,
B. Gómez-Ansón ,
M. Serra-Blasco ,
Y. Vives-Gilabert ,
D. Puigdemont ,
A. Martín-Blanco ,
E. Álvarez ,
V. Pérez  and
M. J. Portella
J. de Diego-Adeliño
Affiliation:
Department of Psychiatry – Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
P. Pires
Affiliation:
Department of Neuroradiology – Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain
B. Gómez-Ansón
Affiliation:
Department of Neuroradiology – Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain
M. Serra-Blasco
Affiliation:
Department of Psychiatry – Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain Port d'Informació Científica (PIC), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Y. Vives-Gilabert
Affiliation:
Port d'Informació Científica (PIC), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
D. Puigdemont
Affiliation:
Department of Psychiatry – Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
A. Martín-Blanco
Affiliation:
Department of Psychiatry – Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
E. Álvarez
Affiliation:
Department of Psychiatry – Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
V. Pérez
Affiliation:
Department of Psychiatry – Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
M. J. Portella*
Affiliation:
Department of Psychiatry – Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
*
* Address for correspondence: M. J. Portella, Ph.D., Department of Psychiatry, Hospital de la Santa Creu i Sant Pau (UAB, CIBERSAM), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Sant Antoni Ma. Claret, 167, 08025 Barcelona, Spain. (Email: mportella@santpau.cat)
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Abstract

Background

Although white-matter abnormalities have been reported in middle-aged patients with major depressive disorder (MDD), few data are available on treatment-resistant MDD and the influence of relevant variables related to clinical burden of illness is far from being well established.

Method

The present study examined white-matter microstructure in a sample of 52 patients with MDD in different stages (treatment-resistant/chronic MDD, n = 18; remitted-recurrent MDD, n = 15; first-episode MDD, n = 19) and 17 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. Groups were comparable in age and gender distribution, and results were corrected for familywise error (FWE) rate.

Results

Widespread significant reductions of fractional anisotropy (FA) – including the cingulum, corpus callosum, superior and inferior longitudinal fascicule – were evident in treatment-resistant/chronic MDD compared with first-episode MDD and controls (p < 0.05, FWE-corrected). Decreased FA was observed within the ventromedial prefrontal region in treatment-resistant/chronic MDD even when compared with the remitted-recurrent MDD group (p < 0.05, FWE-corrected). Longer duration of illness (β = –0.49, p = 0.04) and higher depression severity (at a trend level: β = –0.26, p = 0.06) predicted lower FA in linear multiple regression analysis at the whole-brain level. The number of previous episodes and severity of symptoms were significant predictors when focused on the ventromedial prefrontal area (β = −0.28, p = 0.04; and β = −0.29, p = 0.03, respectively). Medication effects were controlled for in the analyses and results remained unaltered.

Conclusions

Our findings support the notion that disruptions of white-matter microstructure, particularly in fronto-limbic networks, are associated with resistance to treatment and higher current and past burden of depression.

Keywords

Diffusion tensor imagingfractional anisotropymajor depression
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 6 , April 2014 , pp. 1171 - 1182
Copyright
Copyright © Cambridge University Press 2013 

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