Elsevier

Schizophrenia Research

Volume 40, Issue 3, 21 December 1999, Pages 219-227
Schizophrenia Research

Cortical gray matter deficit in patients with bipolar disorder

https://doi.org/10.1016/S0920-9964(99)00063-8Get rights and content

Abstract

Background: cortical gray matter volume deficit and ventricular enlargement are well documented in schizophrenia, but their presence in bipolar disorder is less well established.

Methods: global cortical gray matter, white matter and sulcal CSF, as well as lateral and third ventricular volume measures, were derived from axial MRI brain images obtained on age-matched bipolar (n=9), schizophrenic (n=9), and control (n=16) subjects. All subjects were free of history of alcohol or other substance dependence.

Results: relative to controls, bipolar patients had widespread volume deficits of cortical gray matter but not of cortical white matter. Schizophrenic patients had an even more severe cortical gray matter deficit and greater sulcal and lateral ventricular enlargement than the bipolar patients.

Conclusions: this group of patients with bipolar disorder had a widespread deficit of cortical gray matter similar to, but less pronounced than, that observed in patients with schizophrenia.

Introduction

Narrative reviews of structural neuroimaging studies of patients with mood disorders note a lack of consistent evidence for sulcal and ventricular enlargement (Soares and Mann, 1997). However, meta-analysis (Hedges and Olkin, 1985) has revealed highly statistically significant effect sizes for both sulcal and ventricular enlargement in mood disorders (Elkis et al., 1995). Furthermore, meta-analysis of studies comparing patients with mood disorder and schizophrenia reveal small, but also highly significant, evidence for greater ventricular enlargement in patients with schizophrenia than those with mood disorders (Elkis et al., 1995).

This evidence of gross neuroanatomic deficits in mood disorders raises new questions. For example: are sulci enlarged at the expense of both cortical gray and white matter, or is only one tissue type affected? Is one cortical region more strongly affected than others? Concerning the type of tissue involved, most recent magnetic resonance imaging (MRI) studies have not found a cortical gray matter volume deficit in bipolar disorders (Dupont et al., 1995, Harvey et al., 1994, Pearlson et al., 1997, Schlaepfer et al., 1994, Strakowski et al., 1993a, Zipursky et al., 1997), whereas others have found changes in the quality, if not the quantity, of white matter (Altshuler et al., 1995, Dupont et al., 1995, Woods et al., 1995). Most studies to date have not performed regional analysis of cortical deficits (Soares and Mann, 1997), although the prefrontal cortex would be a target area because of its role in fronto-subcortical neuroanatomic circuits that may underlie mediation of emotional responses and modulation of neurotransmitter systems targeted by antidepressant drugs (Damasio, 1994, Drevets and Todd, 1997). Available studies examining regional data report no evidence for prefrontal gray matter deficits among bipolar disorder patients (Dupont et al., 1995, Zipursky et al., 1997), but one (Dupont et al., 1995) reports suggestive, albeit not conclusive, evidence for a relatively frontal distribution of abnormal white matter in bipolar disorder patients. Recently, a functional imaging study has reported decreased blood flow attributed, at least in part, to reduced gray matter volume in the subgenual prefrontal cortex in bipolar and unipolar patients relative to normal controls (Drevets et al., 1997).

We have developed a reliable and sensitive approach to measure the volume of gray and white matter in the cortex as a whole, as well as in geometrically defined lobar regions. We have used this technique to document normal brain volume development from infancy to old age (Pfefferbaum et al., 1994), volume deficits relative to age and head-size norms in patients with schizophrenia (Sullivan et al., 1998a, Zipursky et al., 1992), alcoholism (Pfefferbaum et al., 1992) and Alzheimer's disease (Fama et al., 1997), as well as differing regional profiles of cortical gray matter deficit in patients with schizophrenia and alcoholism (Sullivan et al., 1998b). In this report, we present new data from a small sample of patients with bipolar disorder. The primary purpose of the study was to determine whether patients with bipolar disorder had deficits in gray or white matter compared with normal controls, and whether there was any evidence for a preferential prefrontal deficit. A secondary purpose was to determine whether any abnormalities in patients with bipolar disorder differed in degree or kind from abnormalities seen in patients with schizophrenia. To do this, we compared patients with bipolar disorder to age-matched samples of patients with schizophrenia and normal controls

Section snippets

Subjects

All study participants gave written informed consent for research participation. Clinical and demographic characteristics of the subject groups are presented below and summarized in Table 1. All subjects were men.

Analysis of raw scores

Raw volumes for each global ROI are summarized in Table 2. Compared with schizophrenic patients, bipolar disorder patients had larger heads [t(16)=4.11, p=0.0008], more gray matter [t(16)=2.71, p=0.015], more white matter [t(16)=2.98, p=0.009], but no significant differences in CSF volumes. Bipolar patients also had less gray matter [t(23)=2.24, p=0.035], more cortical CSF [t(23)=2.24, p=0.029] and larger lateral ventricles [t(23)=2.11, p=0.046] than controls. Schizophrenic patients also had

Discussion

This study compared small samples of age-matched men with bipolar disorder, schizophrenia and healthy controls. Compared with the controls, patients with bipolar disorder had a significant cortical gray matter deficit and enlarged cortical sulci. Lateral ventricles were also enlarged but not significantly so. Schizophrenic patients showed a similar but more pronounced pattern of abnormalities. Thus, on these global brain morphological measures, bipolar disorder patients fell between

Acknowledgements

We would like to thank the staff of the Laboratory of Physiological and Structural Brain Imaging and Mental Health Clinical Research Center for their patient care and invaluable assistance in conducting this research project. In particular, we thank Howard Fenn, M.D., for referral of bipolar disorder patients, Sarah Rawson, M.A., for patient recruitment, Brian Matsumoto, M.A., for image analysis, and Kenneth Chow, M.A., for data processing.

A partial report of these data was presented at the

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    Performance of this study was supported by grants from NIH (MH30854, MH53313, MH58007, AA05965), the Department of Veterans Affairs, and the clinical resources of the Veterans Affairs Palo Alto Health Care System.

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    Present address: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.

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