Cerebral volume asymmetries in schizophrenia and mood disorders: a quantitative magnetic resonance imaging study

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Abstract

Multiple abnormalities of brain structure have been identified in schizophrenia using in vivo neuroimaging methods, but little is known about the diagnostic specificity of these abnormalities. In a prior study of first-episode schizophrenia we found that this group lacked the normal pattern of cerebral volume asymmetries. Data from that study were combined with data from groups of patients with more chronic schizophrenia, and with bipolar and unipolar mood disorders, to determine the specificity of this abnormality to diagnostic subgroups defined by syndromal status or chronicity. The total sample comprised 235 patients (67 healthy volunteers, 81 patients with mood disorders or schizoaffective disorders, and 87 with schizophrenia or schizophreniform disorders). Asymmetries of regional cerebral volumes were measured on coronal magnetic resonance images with 3.1-mm contiguous slices and nominal in-plane resolution of 1 mm×1 mm. Asymmetries differed significantly across groups in the occipito-parietal, prefrontal, and temporal regions. These asymmetries, and a composite index of asymmetry across regions (‘torque’), all showed the same diagnostic group effect, with the schizophrenia group showing the least normal asymmetry, the mood disorder group intermediate asymmetry, and the control group the most marked asymmetry. No other diagnostic subgroup or chronicity effects were apparent. The findings support a ‘continuum’ rather than a ‘diagnostic specificity’ hypothesis, and suggest that the reduction of normal hemispheric asymmetries may mark a neurodevelopmental risk factor for major mental illnesses, and that some syndromal characteristics may be correlated with the degree of deviation from the normal anatomic pattern.

Introduction

An important goal for psychiatric research is to discern the boundaries between syndromes that have different etiologic and pathophysiologic bases. The boundaries that may distinguish schizophrenia as a unique entity have been debated over the last century, with narrower and broader definitions of the syndrome favored in different eras. Recent attention has focused on areas of syndromal and genetic overlap between schizophrenia and the affective psychoses, and several lines of evidence support the concept of a psychotic ‘continuum,’ including schizophrenia, schizoaffective disorder, and both bipolar and unipolar affective psychoses (Baron et al., 1985, Baron and Risch, 1987, Crow, 1990, Crow, 1995, Andreasen and Flaum, 1991, Baron and Gruen, 1991, Minas et al., 1992, Goldstein et al., 1993, Maier et al., 1993, Kendler et al., 1995, Maziade et al., 1995; but see also Tsuang et al., 1983, Parnas et al., 1993). Given the increased availability and improved methods for genetic analysis, it is now particularly critical to define biologically relevant phenotypes, so that transmissible and exogenous risk factors can be distinguished.

Abnormalities of brain structure offer relatively concrete evidence for potentially specific neuropathologic processes that may underlie mental disorders. Both post-mortem and in vivo studies of schizophrenia have revealed a plethora of neuroanatomic abnormalities, including abnormalities in first-episode patients, thus making it clear that these are not artifacts of long-term illness or treatment [for reviews see Bogerts (1997) and Shenton et al. (1997)]. In contrast to schizophrenia research, there have been relatively few quantitative morphometric studies of brain structure in mood disorders [for reviews see Elkis et al. (1995) and Soares and Mann (1997)]. Studies of neuroanatomic abnormalities in Major Depressive Disorder (MDD) have emphasized qualitative methods (i.e. studies of alterations in T2 signal intensities), and included primarily older patients [but for a noteworthy exception see Strakowski et al., 1993a, Strakowski et al., 1993b]. Quantitative studies directly comparing patients with schizophrenia to patients with mood disorders are particularly sparse.

Among the morphometric studies that have been conducted, a few consistent findings have emerged. Ventricular enlargement appears not to show diagnostic specificity, but instead follows a continuum. Individuals with schizophrenia have shown greatest enlargements, while those with mood disorders showed on average less severe, but still significant enlargements with respect to healthy reference groups (Elkis et al., 1995). For other abnormalities that have been well documented in schizophrenia, including sulcal enlargement, diffuse or regionally specific cortical gray matter volume reductions, mesiotemporal volume reductions, and caudate nucleus enlargements, data directly comparing schizophrenia to other psychotic disorders are generally inconclusive about specificity to schizophrenia, due to an absence of evidence (Elkis et al., 1995, Soares and Mann, 1997).

In addition to the study of volumetric abnormalities in key brain regions, attention has been paid to the study of abnormalities in the lateralized distribution of brain abnormalities in the psychoses. Reports have focused on the increased prevalence of abnormalities within the left hemisphere, and on absences or even reversals of the normal patterns of anatomic asymmetry [reviewed by Bilder et al. (1994)]. In a previous report, we described the lack of normal hemispheric volume asymmetries in a sample of individuals with first-episode schizophrenia (Bilder et al., 1994). There have been indications that patients with bipolar disorder have normal asymmetries (Johnstone et al., 1989, Altshuler et al., 1991), and abnormal asymmetry of the posterior superior temporal gyrus was observed in schizophrenia compared to both patients with bipolar disorder and healthy individuals (Pearlson et al., 1997), but not all data are consistent (Swayze et al., 1992). The current study was designed primarily to determine the specificity of abnormal cerebral asymmetry to schizophrenia, in comparison to groups of patients with schizoaffective and mood disorders. A secondary goal was to determine whether there might be distinctions among subgroups of individuals with mood disorders (i.e. between unipolar and bipolar psychoses), or among schizophrenia subgroups defined by chronicity.

Section snippets

Participants

Recruitment of participants for this study followed two streams. One recruitment stream involved subjects in the first episode of psychosis [for complete description of inclusion/exclusion criteria see Lieberman et al., 1992, Lieberman et al., 1993]. This sample included individuals with schizophrenia, schizoaffective, and schizophreniform disorders by DSM-III-R criteria, based on initial SADS interviews, medical and laboratory tests, and then extensive repeated follow-up interviews and rating

Results

Sample characteristics for the broad diagnostic groups are shown in Table 1. The groups did not differ significantly in sex composition or age at first treatment, but did differ in age (the schizophrenia group was slightly younger than the other groups) and education (the control group differed from the other groups). The possible effects of these differences were examined in subsequent analyses. The broad mood disorders group comprised subgroups with Major Depressive Disorder (n=25: with

Discussion

The results suggest that the normal pattern of cerebral volume asymmetries, with left posterior and right anterior regions larger than their contralateral homologues, is attenuated in groups of patients comprising broadly defined mood disorders and schizophrenia spectrum disorders. These results both add to an emerging literature about neuroanatomic abnormalities in mood disorders, and highlight the lack of diagnostic specificity of this neuroanatomic abnormality to schizophrenia. The findings

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