Background
We conducted a meta-analysis of gray matter abnormalities in bipolar disorder (BD)
using voxel-based morphometry studies to help clarify the structural abnormalities
underpinning this condition.
Methods
A systematic review was conducted for voxel-based morphometry studies of patients
with BD. Meta-analyses of gray matter differences between BD and control subjects
were undertaken using “signed differential mapping,” a novel method that, in contrast
to previously used techniques, allows inclusion of negative findings and ensures that
single studies do not exert undue influence on the results. Meta-regression and subgroup
analyses were used to examine the effect of moderator variables on gray matter abnormalities.
Results
A total of 21 studies comparing gray matter volumes of 660 BD patients and 770 healthy
control subjects were included. Gray matter reduction in left rostral anterior cingulate
cortex (ACC) and right fronto-insular cortex was associated with BD. Fronto-insular
cortex abnormality was not evident in early phases of the illness. In chronic patients,
longer duration of illness was associated with increased gray matter in a cluster
that included basal ganglia, subgenual ACC, and amygdala. Lithium treatment was associated
with enlargement of ACC gray matter volumes, which overlapped with the region where
gray matter was reduced in BD.
Conclusions
The most robust gray matter reductions in BD occur in anterior limbic regions, which
may be related to the executive control and emotional processing abnormalities seen
in this patient population. Clinical factors such as illness duration and lithium
treatment also impact on case-control comparisons of gray matter volume.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder.Biol Psychiatry. 2004; 56: 411-417
- Meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder.Arch Gen Psychiatry. 2008; 65: 1017-1032
- Magnetic resonance imaging studies in bipolar disorder and schizophrenia: Meta-analysis.Br J Psychiatry. 2009; 195: 194-201
- Voxel-based morphometry—The methods.Neuroimage. 2000; 11: 805-821
- A voxel-based morphometric study of ageing in 465 normal adult human brains.Neuroimage. 2001; 14: 21-36
- Meta-analysis of the functional neuroanatomy of single-word reading: Method and validation.Neuroimage. 2002; 16: 765-780
- Meta-analysis of functional neuroimaging data: Current and future directions.Soc Cogn Affect Neurosci. 2007; 2: 150-158
- Voxel-wise meta-analysis of grey matter changes in obsessive-compulsive disorder.Br J Psychiatry. 2009; 195: 393-402
- Mapping grey matter reductions in schizophrenia: An anatomical likelihood estimation analysis of voxel-based morphometry studies.Schizophr Res. 2009; 108: 104-113
- Meta-analysis of gray matter anomalies in schizophrenia: Application of anatomic likelihood estimation and network analysis.Biol Psychiatry. 2008; 64: 774-781
- Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs.Am J Psychiatry. 1994; 151: 1430-1436
- Reduced left anterior cingulate volumes in untreated bipolar patients.Biol Psychiatry. 2004; 56: 467-475
- A longitudinal study of the effects of lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients.J Clin Psychiatry. 2009; 70: 699-705
- Prefrontal gray matter increases in healthy individuals after lithium treatment: A voxel-based morphometry study.Neurosci Lett. 2007; 429: 7-11
- Progressive gray matter loss in patients with bipolar disorder.Biol Psychiatry. 2007; 62: 894-900
- Preliminary evidence for progressive prefrontal abnormalities in adolescents and young adults with bipolar disorder.J Int Neuropsychol Soc. 2009; 15: 476-481
- A study of bipolar disorder using magnetization transfer imaging and voxel-based morphometry.Brain. 2004; 127: 2433-2440
- Reduction of cingulated gray matter density in poor outcome bipolar illness.Psychiatry Res. 2004; 130: 153-159
- Regional brain gray matter volume differences in patients with bipolar disorder as assessed by optimized voxel-based morphometry.Biol Psychiatry. 2004; 55: 1154-1162
- Frontal lobe gray matter density decreases in bipolar I disorder.Biol Psychiatry. 2004; 55: 648-651
- Voxel-based morphometry of patients with schizophrenia or bipolar disorder and their unaffected relatives.Biol Psychiatry. 2004; 56: 544-552
- Changes in gray matter volume in patients with bipolar disorder.Biol Psychiatry. 2005; 58: 151-157
- Frontotemporal alterations in pediatric bipolar disorder: Results of a voxel-based morphometry study.Arch Gen Psychiatry. 2005; 62: 734-741
- Diagnosis-related regional gray matter loss over two years in first episode schizophrenia and bipolar disorder.Biol Psychiatry. 2005; 58: 713-723
- Regional volume deviations of brain structure in schizophrenia and psychotic bipolar disorder: Computational morphometry study.Br J Psychiatry. 2005; 186: 369-377
- Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry.Neuroimage. 2006; 30: 485-497
- Voxel-based study of structural changes in first-episode patients with bipolar disorder.Biol Psychiatry. 2007; 61: 776-781
- Regional gray matter changes in bipolar disorder: A voxel-based morphometric study.Aust N Z J Psychiatry. 2007; 41: 327-336
- A magnetic resonance imaging study of mood stabilizer- and neuroleptic-naïve first-episode mania.Bipolar Disord. 2007; 9: 693-697
- Structural brain correlates of response inhibition in bipolar disorder I.J Psychopharmacol. 2008; 22: 138-143
- Regional gray matter volume deficits in adolescents with first-episode psychosis.J Am Acad Child Adolesc Psychiatry. 2008; 47: 1311-1320
- No change to grey and white matter volumes in bipolar I disorder patients.Eur Arch Psychiatry Clin Neurosci. 2008; 258: 345-349
- Reduced gray matter volume in ventral prefrontal cortex but not amygdala in bipolar disorder: Significant effects of gender and trait anxiety.Psychiatry Res. 2009; 171: 54-68
- Regional brain gray matter abnormalities in patients with bipolar II disorder: A comparison study with bipolar I patients and healthy controls.Neurosci Lett. 2009; 456: 44-48
- Dissociable brain structural changes associated with predisposition, resilience, and disease expression in bipolar disorder.J Neurosci. 2009; 29: 10863-10868
- Structural abnormalities of ventrolateral and orbitofrontal cortex in patients with familial bipolar disorder.Bipolar Disord. 2009; 11: 135-144
- Prefrontal-temporal gray matter deficits in bipolar disorder patients with persecutory delusions.J Affect Disord. 2010; 120: 54-61
- Voxel-based morphometry in adolescents with bipolar disorder: First results.Psychiatry Res. 2004; 131: 57-69
- Quantitative evaluation of brain magnetic resonance images using voxel baed morphometry and baysian theorem for patients with bipolar disorder.Med Biol Eng. 2008; 28: 127-133
- Genetic liability to schizophrenia or bipolar disorder and its relationship to brain structure.Am J Med Genet B. 2006; 141B: 76-83
- Neuroanatomic comparison of bipolar adolescents with and without cannabis use disorders.J Child Adolesc Psychpharmacol. 2008; 18: 557-563
- Dorsolateral and dorsomedial prefrontal gray matter density changes associated with bipolar depression.Psychiatry Res. 2009; 172: 200-204
- Development and validation of MIX: Comprehensive free software for meta-analysis of causal research data.BMC Med Res Methodol. 2006; 6: 50
- Co-Planar Stereotaxic Atlas of the Human Brain.Thieme, New York1988
- Bias between MNI and Talairach coordinates analyzed using the ICBM-152 brain template.Hum Brain Mapp. 2007; 28: 1194-1205
- Coordinate-based activation likelihood estimation meta-analysis of neuroimaging data: A random-effects approach based on empirical estimates of spatial uncertainty.Hum Brain Mapp. 2009; 30: 2907-2926
- Meta-analysis of neuroimaging data: A comparison of image-based and coordinate-based pooling of studies.Neuroimage. 2009; 42: 810-823
- In vivo evidence for early neurodevelopmental anomaly of the anterior cingulate cortex in bipolar disorder.Acta Psychiatr Scand. 2007; 116: 467-472
- Anatomical abnormalities of the anterior cingulate and paracingulate cortex in patients with bipolar I disorder.Psychiatry Res. 2008; 162: 123-132
- Reduced left anterior cingulate volumes in untreated bipolar patients.Biol Psychiatry. 2004; 56: 467-475
- Cingulate cortex anatomical abnormalities in children and adolescents with bipolar disorder.Am J Psychiatry. 2005; 162: 1637-1643
- Anterior cingulate dysfunction: Implications for psychiatric disorders?.J Psychiatry Neurosci. 2003; 28: 350-354
- Cognitive endophenotypes of bipolar disorder: A meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives.J Affect Disord. 2009; 113: 1-20
- Emotional bias and inhibitory control processes in mania and depression.Psychol Med. 1999; 29: 1307-1321
- Neuropsychology of bipolar disorder.Br J Psychiatry Suppl. 2001; 41: s120-s127
- Decreased prefrontal, anterior cingulate, insula, and ventral striatal metabolism in medication-free depressed outpatients with bipolar disorder.J Psychiatr Res. 2009; 43: 181-188
- Prefrontal function and activation in bipolar disorder and schizophrenia.Am J Psychiatry. 2008; 165: 378-384
- Bilateral decrease in ventrolateral prefrontal cortex activation during motor response inhibition in mania.J Psychiatr Res. 2009; 43: 432-441
- Neural activity of the anterior insula in emotional processing depends on the individuals' emotional susceptibility.Hum Brain Mapp. 2008; 29: 363-373
- Interoception: The sense of the physiological condition of the body.Curr Opin Neurobiol. 2003; 13: 500-505
- Inhibition and the right inferior frontal cortex.Trends Cogn Sci. 2004; 8: 170-177
- Evidence for deficit in tasks of ventral, but not dorsal, prefrontal executive function as an endophenotypic marker for bipolar disorder.Biol Psychiatry. 2005; 58: 838-839
- Circuitry and functional aspects of the insular lobe in primates including humans.Brain Res Rev. 1996; 22: 229-244
- Relationship between cingulo-insular functional connectivity and autistic traits in neurotypical adults.Am J Psychiatry. 2009; 166: 891-899
- How do you feel—now?.Nat Rev Neurosci. 2009; 10: 59-70
- A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks.Proc Natl Acad Sci U S A. 2008; 105: 12569-12574
- Two systems of resting state connectivity between the insula and cingulate cortex.Hum Brain Mapp. 2009; 30: 2731-2745
- The interaction of emotional and cognitive neural systems in emotionally guided response inhibition.Neuroimage. 2006; 31: 468-475
- Dendritic architecture of the von economo neurons.Neuroscience. 2006; 141: 1107-1112
- Lithium and increased cortical gray matter—more tissue or more water?.Biol Psychiatry. 2008; 62: 7-16
- Anterior cingulate subregion volumes and executive function in bipolar disorder.Bipolar Disord. 2006; 8: 281-288
- Reduced subgenual cingulated volumes in mood disorders: A meta-analysis.J Psychiatry Neurosci. 2008; 33: 91-99
- Hippocampal and amygdala volumes according to psychosis stage and diagnosis: A magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals.Arch Gen Psychiatry. 2006; 63: 139-149
- Meta-analysis of amygdala volumes in children and adolescents with bipolar disorder.J Am Acad Child Adolesc Psychiatry. 2008; 47: 1289-1298
- Amygdala volumes in mood disorders—meta-analysis of magnetic resonance volumetry studies.J Affect Disord. 2009; 115: 395-410
Article info
Publication history
Published online: March 19, 2010
Accepted:
January 15,
2010
Received in revised form:
January 12,
2010
Received:
December 1,
2009
Identification
Copyright
© 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
