Cortical gray matter deficit in patients with bipolar disorder☆
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
References (31)
- et al.
Brain dysmorphology in adults with congenital rubella plus schizophrenia-like symptoms
Biol. Psychiatry
(1995) - et al.
Gray matter volume deficits in young onset schizophrenia are independent of age of onset
Biol. Psychiatry
(1996) - et al.
Cortical gray matter volume deficits in schizophrenia: a replication
Schiz. Res.
(1996) - et al.
Correction for head size in brain-imaging measurements
Psychiatry Res. Neuroimaging
(1993) - et al.
Correction for head size in brain-imaging measurements: Letter to editor
Psychiatry Res. Neuroimaging
(1993) - et al.
Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder
Biol. Psychiatry
(1997) - et al.
A quantitative magnetic resonance imaging study of cerebral and cerebellar gray matter volume in primary unipolar major depression: relationship to treatment response and clinical severity
Biol. Psychiatry
(1997) - et al.
The anatomy of mood disorders — review of structural neuroimaging studies
Biol. Psychiatry
(1997) - et al.
Structural brain abnormalities in first-episode mania
Biol. Psychiatry
(1993) - et al.
MRI subcortical signal hyperintensities in mania at first hospitalization
Biol. Psychiatry
(1993)
Age-related decline in MRI volumes of temporal lobe gray matter but not hippocampus
Neurobiol. Aging
Patterns of regional cortical dysmorphology distinguishing schizophrenia and chronic alcoholism
Biol. Psychiatry
Age-related MRI abnormalities in bipolar illness: a clinical study
Biol. Psychiatry
Deficits in gray matter volume are present in schizophrenia but not bipolar disorder
Schiz. Res.
T-2 hyperintensities in bipolar disorder: magnetic resonance imaging comparison and literature meta-analysis
Am. J. Psychiatry
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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.