Accelerated gray and white matter deterioration with age in schizophrenia

Vanessa L Cropley, Paul Klauser, Rhoshel K Lenroot, Jason Bruggemann, Suresh Sundram, Chad Bousman, Avril Pereira, Maria A Di Biase, Thomas W Weickert, Cynthia Shannon Weickert, Christos Pantelis, Andrew Zalesky

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective: Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remain sun clear. The authors sought tomeasure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Method: Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Betweengroup differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Results: Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60% steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. Conclusions: The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.

Original languageEnglish
Pages (from-to)286-295
Number of pages10
JournalAmerican Journal of Psychiatry
Volume174
Issue number3
DOIs
Publication statusPublished - 1 Mar 2017
EventSchizophrenia International Research Society Conference: Deconstructing Schizophrenia Towards Targeted Treatment - Firenze Fiera Congress Center, Florence, Italy
Duration: 2 Apr 20166 Apr 2016
Conference number: 5th

Cite this

Cropley, Vanessa L ; Klauser, Paul ; Lenroot, Rhoshel K ; Bruggemann, Jason ; Sundram, Suresh ; Bousman, Chad ; Pereira, Avril ; Di Biase, Maria A ; Weickert, Thomas W ; Weickert, Cynthia Shannon ; Pantelis, Christos ; Zalesky, Andrew. / Accelerated gray and white matter deterioration with age in schizophrenia. In: American Journal of Psychiatry. 2017 ; Vol. 174, No. 3. pp. 286-295.
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abstract = "Objective: Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remain sun clear. The authors sought tomeasure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Method: Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Betweengroup differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Results: Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8{\%} in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60{\%} steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. Conclusions: The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.",
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Cropley, VL, Klauser, P, Lenroot, RK, Bruggemann, J, Sundram, S, Bousman, C, Pereira, A, Di Biase, MA, Weickert, TW, Weickert, CS, Pantelis, C & Zalesky, A 2017, 'Accelerated gray and white matter deterioration with age in schizophrenia' American Journal of Psychiatry, vol. 174, no. 3, pp. 286-295. https://doi.org/10.1176/appi.ajp.2016.16050610

Accelerated gray and white matter deterioration with age in schizophrenia. / Cropley, Vanessa L; Klauser, Paul; Lenroot, Rhoshel K; Bruggemann, Jason; Sundram, Suresh; Bousman, Chad; Pereira, Avril; Di Biase, Maria A; Weickert, Thomas W; Weickert, Cynthia Shannon; Pantelis, Christos; Zalesky, Andrew.

In: American Journal of Psychiatry, Vol. 174, No. 3, 01.03.2017, p. 286-295.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Accelerated gray and white matter deterioration with age in schizophrenia

AU - Cropley, Vanessa L

AU - Klauser, Paul

AU - Lenroot, Rhoshel K

AU - Bruggemann, Jason

AU - Sundram, Suresh

AU - Bousman, Chad

AU - Pereira, Avril

AU - Di Biase, Maria A

AU - Weickert, Thomas W

AU - Weickert, Cynthia Shannon

AU - Pantelis, Christos

AU - Zalesky, Andrew

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N2 - Objective: Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remain sun clear. The authors sought tomeasure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Method: Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Betweengroup differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Results: Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60% steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. Conclusions: The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.

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