Complex pattern of cortical thinning in schizophrenia: Results from an automated surface based analysis of cortical thickness

https://doi.org/10.1016/j.pscychresns.2010.01.008Get rights and content

Abstract

A considerable body of evidence from structural brain imaging studies suggests that patients with schizophrenia have significant alterations of gray matter density. Additionally, recently developed surface-based analysis approaches demonstrate reduced cortical thickness in patients with schizophrenia. However, the number of studies employing this relatively new method is still limited. Specifically, little is known about changes in cortical thickness in schizophrenia patients whose duration of illness is relatively short. Therefore, the present study sought to examine cortical thickness in a large sample of patients with adult onset schizophrenia and an average duration of illness of 4.4 years, using an automated analysis method over the entire cortex. A significantly decreased cortical thickness in prefrontal and temporolimbic regions as well as parieto-occipital cortical areas was hypothesized. A sample of 58 patients with schizophrenia and 58 age- and sex-matched healthy controls was investigated using high-resolution magnetic resonance imaging (MRI) and an automated algorithm for extraction of the cortical surface in order to assess local cortical thinning across the entire cerebrum. Significant reduction of cortical thickness in schizophrenia was found in a spatially complex pattern of focal anatomical regions. This pattern comprised the dorsolateral prefrontal cortex as well as the medial prefrontal cortex, lateral temporal cortices, left entorhinal cortex, posterior cingulate cortex, precuneus and lingual cortex, bilaterally. A complex fronto-temporo-parietal pattern of reduced cortical thickness in schizophrenia was observed. This pattern is consistent with a disruption of neurofunctional networks previously implicated in the pathophysiology of schizophrenia.

Introduction

There is a broad base of evidence suggesting morphologic alterations in patients with schizophrenia. According to recent reviews and meta-analyses, the left temporal and frontal areas seem to be predominantly affected by decreases in gray matter density (Honea et al., 2005, Williams, 2008). However, there are also a substantial number of studies which could not detect any alterations in a subset of regions including the medial temporal lobe (Ananth et al., 2002) and medial frontal gyrus (Wright et al., 1999).

Recently, automated surface-based approaches have developed in order to allow for a closer examination of cortical surface characteristics between patient and control groups. These approaches take into account the intrinsic two-dimensional structure and highly folded geometry of the cortex (Dale et al., 1999, Fischl et al., 1999). Thus, whereas the voxel based morphometry (VBM) approach is primarily directed towards gray matter density, surface-based analysis complements the available analysis strategies by including morphological shape analysis either in terms of thickness or curvature. Measurement of cortical thickness is of great interest for the investigation of morphological alterations that are attributed to putative pathogenetic neurodevelopmental mechanisms currently proposed to be related to schizophrenia (Rapoport et al., 2005, Fatemi and Folsom, 2009). Automated methods for regional parcellation and surface-based cortical shaping analyses efficiently extract information about the entire cortex. While a region of interest analysis is restricted to an a priori defined search space of potential anatomical alterations, entire cortex analyses can examine the entire surface for morphological changes in an exploratory manner. In addition, the quantification of cortical thinning across the entire cortex sheds light on how strongly the different brain regions are affected.

In first episode schizophrenia, cortical thinning was previously demonstrated in frontal, cingulate, temporal, occipital, and parietal cortices (Narr et al., 2005a, Narr et al., 2005b). Venkatasubramanian et al. (2008) demonstrated prefrontal cortical thinning in antipsychotic-naive patients with schizophrenia utilising a surface-based approach. In addition, first episode patients investigated using a surface-based method demonstrated cortical thinning in the anterior cingulate cortex (Fornito et al., 2008).

To date, few studies have examined cortical thickness in multi-episode, adult onset schizophrenia. They demonstrated decreased cortical thickness mainly in prefronto-temporal areas (Kuperberg et al., 2003, Nesvag et al., 2008). However, these studies showed some heterogeneity regarding the affected anatomical regions. While the study of Nesvag et al. (2008) demonstrated cortical thinning in superiorfrontal regions, this area was mostly spared according to the study of Kuperberg et al. (2003). Conversely, the entire cortex analyses of Kuperberg et al. (2003) revealed lateral occipital regions to be affected, which were not affected in Nesvag et al. (2008). These heterogeneities might be attributable to scanner modalities such as differences in MRI sequences as well as clinical and demographic characteristics of the study group.

Nesvag et al. (2008) and Kuperberg et al. (2003) investigated chronic patients with a duration of illness of 16 years or longer. The investigation of cortical thickness of patients with schizophrenia in the short/medium course of the illness might therefore extend our knowledge of cortical thickness aberrations in schizophrenia. In order to detect and quantify even subtle cortical alterations in the short/medium term of schizophrenia, the present study sought to examine cortical thickness in a larger sample of patients with adult onset schizophrenia in the short/medium course of the illness using an entire cortex analysis and an automated surface-based approach. Based on the previous literature (Kuperberg et al., 2003, Narr et al., 2005a, Narr et al., 2005b, Nesvag et al., 2008), it was hypothesized that cortical thinning in schizophrenia patients would be detectable predominantly in prefronto-temporal as well as parieto-occipital regions.

Section snippets

Participants

A total of 58 patients with schizophrenia and 58 matched healthy controls matched for age and gender were included in the study. All subjects were right-handed (Annett, 1967). Diagnoses were established by a clinical psychiatrist (M. R.) based on the Structured Clinical Interview for DSM-IV, and these diagnoses were subsequently confirmed by two independent psychiatrists (R. S. and C. S.). All patients met the DSM-IV criteria for schizophrenia and had no second psychiatric diagnosis. Patients

FDR approach

The cortex was significantly (FDR < 0.05) thinner in patients with schizophrenia compared to healthy controls, predominantly in temporal and prefrontal cortical regions (Fig. 1), but also parietal and occipital cortices. Significant (FDR < 0.05) differences in cortical thickness were found for both hemispheres in superior frontal, rostral middle frontal, medial orbitofrontal, superior temporal, middle temporal, inferior temporal, fusiform, supramarginal, precuneus, lateral occipital, lingual, and

Discussion

The present study investigated and quantified alterations in cortical thickness in a sample of patients with adult onset schizophrenia in the short/medium course of the illness. As hypothesized, the results revealed significant cortical thinning in patients compared to healthy controls mainly in prefronto-temporal cortical areas. Additionally, cortical regions of the medial surface were affected. These included the posterior cingulate cortex, temporolimbic cortex, and precuneus.

The performed

Acknowledgments

This work was supported by the Bundesministerium für Bildung und Forschung, BMBF Grant 01GW0740.

References (57)

  • U.K. Haukvik et al.

    Cerebral cortical thickness and a history of obstetric complications in schizophrenia

    Journal of Psychiatric Research

    (2009)
  • P. Kalus et al.

    New evidence for involvement of the entorhinal region in schizophrenia: a combined MRI volumetric and DTI study

    Neuroimage

    (2005)
  • K. Koch et al.

    Temporal modeling demonstrates preserved overlearning processes in schizophrenia: an fMRI study

    Neuroscience

    (2007)
  • K. Koch et al.

    Fronto-striatal hypoactivation during correct information retrieval in patients with schizophrenia: an fMRI study

    Neuroscience

    (2008)
  • G. Lawyer et al.

    Investigating possible subtypes of schizophrenia patients and controls based on brain cortical thickness

    Psychiatry Research

    (2008)
  • S.A. Mitelman et al.

    Cortical intercorrelations of frontal area volumes in schizophrenia

    Neuroimage

    (2005)
  • S.A. Mitelman et al.

    Cortical intercorrelations of temporal area volumes in schizophrenia

    Schizophrenia Research

    (2005)
  • K.L. Narr et al.

    Cortical thinning in cingulate and occipital cortices in first episode schizophrenia

    Biological Psychiatry

    (2005)
  • R. Nesvag et al.

    Regional thinning of the cerebral cortex in schizophrenia: effects of diagnosis, age and antipsychotic medication

    Schizophrenia Research

    (2008)
  • P.C. Nopoulos et al.

    Sex differences in the absence of massa intermedia in patients with schizophrenia versus healthy controls

    Schizophrenia Research

    (2001)
  • A.E. Pinkham et al.

    Neural bases for impaired social cognition in schizophrenia and autism spectrum disorders

    Schizophrenia Research

    (2008)
  • R. Schlosser et al.

    Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling

    Neuroimage

    (2003)
  • R.G. Schlosser et al.

    Inefficient executive cognitive control in schizophrenia is preceded by altered functional activation during information encoding: an fMRI study

    Neuropsychologia

    (2008)
  • N. Stefanis et al.

    Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications

    Biological Psychiatry

    (1999)
  • N.L. Voets et al.

    Evidence for abnormalities of cortical development in adolescent-onset schizophrenia

    Neuroimage

    (2008)
  • H.C. Whalley et al.

    Functional imaging as a predictor of schizophrenia

    Biological Psychiatry

    (2006)
  • I.C. Wright et al.

    Mapping of grey matter changes in schizophrenia

    Schizophrenia Research

    (1999)
  • H. Ananth et al.

    Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry

    American Journal of Psychiatry

    (2002)
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