Elsevier

Biological Psychiatry

Volume 54, Issue 4, 15 August 2003, Pages 418-426
Biological Psychiatry

Original article
Gyrification abnormalities in childhood- and adolescent-onset schizophrenia

https://doi.org/10.1016/S0006-3223(03)00065-9Get rights and content

Abstract

Background

Gyrification is an important index of brain development. We used magnetic resonance scanning technology to compare brain surface morphology and measures of gyrification in children and adolescents with a schizophrenia spectrum disorder and in age-equivalent healthy controls.

Methods

Magnetic resonance scans were obtained from 42 patients and 24 healthy controls, mean age 17.7 years for both groups. We employed novel quantitative measures of brain morphology, including cortical thickness and a variety of indices of sulcal and gyral curvature. We examined these measures in the whole brain and in the frontal, temporal, parietal, and occipital lobes.

Results

There were significant decreases in cortical thickness in the patients. This was most pronounced in the cortical tissue that underlies the sulci. The patient group had significantly more flattened curvature in the sulci and more steeped or peaked curvature in the gyri.

Conclusions

This study quantitatively examines cortical thickness and surface morphology in children and adolescents with schizophrenia. Patients with schizophrenia demonstrated patterns of brain morphology that were distinctly different from healthy controls. In light of current theories of the formation of gyri and sulci, these changes may reflect aberrations in cerebral and subcortical connectivity.

Introduction

The fact that the typical age of onset for schizophrenia is in the late teens and early 20s may provide important clues as to its pathophysiology and etiology. A relatively broad consensus has emerged that schizophrenia arises at least in part due to abnormalities in brain development Lewis and Levitt 2002, Woods 1998. Brain development and maturation occur as a consequence of orderly processes that begin in utero and continue into the early 20s or later: neuronal differentiation, neuronal migration, axon formation and dendritic proliferation, synaptogenesis, myelination, pruning, apoptosis, and activity-dependent changes Huttenlocher 1979, Huttenlocher and de Courten 1987, Huttenlocher et al 1982, Lombroso 1998, Naegele and Lombroso 1998, Sidman and Rakic 1973, Yakovlev and Lecours 1967. The consequences of these processes can be partially tracked in vivo through structural imaging, using measures of cortical thickness, gray matter (GM) and white matter (WM) volume, and gyrification patterns and indices Carman et al 1995, Magnotta et al 1999b, Sisodiya et al 1996, Sisodiya and Free 1997, Van Essen 1997, Van Essen and Drury 1997. Disease-related abnormalities may also be tracked using such measures, as well as via the observation of an increased rate of neurodevelopmental anomalies such as ectopic gray matter or dysgenesis or agenesis of structures or regions Nopoulos et al 1995, Nopoulos et al 1996, Swayze et al 1990, Swayze et al 1997.

Evidence suggesting that schizophrenia is primarily a neurodevelopmental disorder comes from multiple sources. An increased rate of neurodevelopmental abnormalities (e.g., gray matter heterotopias) provides relatively direct evidence. More indirect evidence includes studies of the time window before onset that have identified the presence of premorbid indicators of dysfunction before the onset of the full syndrome Albee et al 1964, Done et al 1994, Friedman et al 1999, Fuller et al 2002, Goldfarb 1967, Jones et al 1994, Murray et al 1992, Walker and Lewine 1990, Walker et al 1994. The presence of structural and functional brain abnormalities in first episode patients at the time of index evaluation also supports a primary neurodevelopmental disorder in schizophrenia Andreasen 1997, Bogerts et al 1990, DeLisi et al 1990, DeLisi et al 1991, DeLisi et al 1994, James et al 2002, Lieberman et al 1992, Lieberman et al 1993, Nopoulos et al 1995, Schulz et al 1982, Schulz et al 1983a. This indirect evidence is based on the assumption that the measurable abnormalities have probably been present for some time before onset of the illness.

Imaging tools have been used to study brain structure and function since the 1980s, beginning with a report of increased ventricular size in schizophrenia using computerized tomography (CT) scanning (Johnstone et al 1976), a finding that has subsequently been consistently replicated with both CT and magnetic resonance (MR) Andreasen et al 1982a, Andreasen et al 1982b, Andreasen et al 1990, DeLisi et al 1983, Flaum et al 1990, James et al 1999, Nasrallah et al 1986, Pfefferbaum et al 1988, Rapoport et al 1997, Reiss et al 1983, Reveley 1985, Schulz et al 1982, Schulz et al 1983b. Several years after the initial description of ventricular enlargement in adults, the finding was replicated in an adolescent population using CT Schulz et al 1982, Schulz et al 1983a and was also relatively recently replicated in a childhood-onset schizophrenia (COS) population Frazier et al 1996, Rapoport et al 1997 using MR; however, the flexibility and power of MR imaging now permits scientists to address many additional questions about the types of brain abnormalities that occur in schizophrenia, which can potentially illuminate the mechanisms of the illness. For example, studies have also reported a decrease in total brain tissue volume Frazier et al 1996, Rapoport et al 1997 and GM in the frontal, temporal, parietal, and occipital lobes (Rapoport et al 1999), decreased size of the cerebellar vermis, and a decrease in thalamic size Dasari et al 1999, Frazier et al 1996, Rapoport et al 1997. A recent longitudinal study of a small sample of COS patients suggests that the cortical abnormalities may shift and progress over time, with a movement from parietal to frontal regions (Thompson et al 2001). Integrating these varied findings in the context of a changing and developing child and adolescent brain presents conceptual challenges.

To address some of these challenges, we have recently developed a group of automated and well-validated quantitative measures that permit tracking of cortical development. In particular, we have developed measures of cortical depth and surface features such as indices of sulcal and gyral curvature Magnotta et al 1999a, Magnotta et al 2000. Such gyrification measures are promising for yielding information about neurodevelopmental mechanisms. These methods can be used to explore the mechanisms that drive brain maturation and specifically gyrification, raising the hope that they may eventually be used to more precisely identify the time of onset of neural abnormalities. In this report, using these novel measures of gyrification, we evaluate brain morphology in a large group of children and adolescents with schizophrenia and a sample of healthy controls.

Section snippets

Subjects

The patient group consisted of 42 subjects between the ages of 12 and 19 with a schizophrenia spectrum disorder. Exclusion criteria for the patient group consisted of severe head injury resulting in loss of consciousness; neurologic disorders such as epilepsy, tuberous sclerosis, or cerebral palsy; and intelligence quotient (IQ) less than 70. Intelligence quotient was screened using the National Adult Reading Test (NART) for both the patient and control groups. Each subject was evaluated using

Surface measures

A MANCOVA of the surface morphology variables was significantly different between patients and controls (p = .05). Analyses of covariance with age, gender, and TBC as a covariate demonstrated differences in the measures of both the gyral (p = .01) and sulcal (p = .02) curvature indices and in cortical thickness (p = .05). Data are shown in Table 3. The differences in the cortical thickness and curvature indices remained significant when controlling for age and gender alone. The cortical

Discussion

This study utilizes novel measures to quantify the thickness of the cortex and the extent of gyrification in childhood- and adolescent-onset schizophrenia compared to controls. Additionally, the technique is able to separate the gyral and sulcal regions, which have a different histology (Welker 1990). These young patients demonstrated a variety of general and regional abnormalities when compared to healthy volunteers.

First, the patients with schizophrenia had a reduction in the average cortical

Acknowledgements

The present study was performed at the University of Iowa, Iowa City, Iowa, under the following grants support: MH31593, MH40856, MH19113, and MHCRC43271. This research was presented at the 8th International Congress on Schizophrenia Research, April 28 to May 2, 2001, Whistler, British Columbia, Canada.

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