Altered White Matter/Gray Matter Proportions in the Striatum of Patients With Schizophrenia: A Volumetric MRI Study

Tamagaki, Chiharu; Sedvall, Göran; Jönsson, Erik G.; Okugawa, Gaku; Hall, Håkan; Pauli, Stefan; Agartz, Ingrid

doi:10.1176/appi.ajp.162.12.2315

Cited by 52 publications

(37 citation statements)

References 36 publications

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“…Gray and white matter volumes of segmented striatal structures have been examined in the present subject material and we found evidence for an altered ratio of white to gray matter in patients compared with healthy control subjects although the total volumes were unchanged [Tamagaki et al, 2005]. In the present study, patients homozygous for the 270 C/T C allele displayed larger total caudate volumes than those carrying the C/T genotype.…”

Section: Discussionsupporting

confidence: 53%

“…The direction of volume size in the patient group was not consistent with the one found in the healthy control subjects. In the previous study on striatal volumes, we found lower white to gray matter ratios in the striatum of patients with increased gray matter volumes of the putamen in the patients and corresponding reductions of the white matter of the caudate and the accumbens nuclei [Tamagaki et al, 2005]. In analogy with the previous reasoning, the BDNF À633 T/A polymorphism, or a gene variant in linkage disequilibrium with it, may be influential to gray matter putamen size and function and has a differential effect in schizophrenic patients compared with healthy control subjects.…”

Section: Discussionmentioning

confidence: 55%

“…From the same subset of subjects, striatal regions, that is, caudate, putamen, and accumbens nuclei, were examined. Differences across subject groups in the total volume of these structures were not demonstrated, but white matter to gray matter ratios were lower in the schizophrenic patients of both genders [Tamagaki et al, 2005].…”

Section: Previously Reported Brain Abnormalities In the Current Subjementioning

confidence: 73%

“…Structures that could not at the time be reliably automatically separated, (e.g., cerebellar vermis substructures [Okugawa et al, 2003a], the detailed delineation of the cerebellar hemispheres [Okugawa et al, 2003a], the accumbens nuclei [Tamagaki et al, 2005], and the hippocampus [Agartz et al, 1999]) were manually outlined according to guidelines previously reported, with the exception that the white matter of the fimbria was excluded in the hippocampus delineation. All segmentation, editing, and tracing were performed by two psychiatrists in post-doctoral positions, who were especially trained for the task.…”

Section: Scan Post Processingmentioning

confidence: 99%

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BDNF gene variants and brain morphology in schizophrenia

Agartz

Sedvall

Terenius

et al. 2006

American J of Med Genetics Pt B

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The objective was to investigate putative associations between brain-derived neurotrophic factor gene (BDNF) polymorphisms and brain morphology in patients with schizophrenia and healthy control subjects. Four BDNF polymorphisms were genotyped and analyzed versus 39 brain volume measures in 96 patients with schizophrenia or schizoaffective disorder and 104 healthy subjects. In all subjects, quantitative data on segmented gray, white, and cerebrospinal fluid (CSF) tissue class volumes of total brain and major cerebral lobes including ventricular CSF were obtained using magnetic resonance imaging (MRI). In a randomly selected subset of this population (n = 101-122), MR volumes from cerebellar tonsil, hemispheres, and vermis subregions, striatal structures, hippocampus, and corpus callosum were also measured. The BDNF 11757 G/C polymorphism was highly significantly associated with frontal gray matter volume variation in patients alone and in patients and control subjects combined. In patients only, the 270 C/T polymorphism was associated with total caudate volume. Significant associations were demonstrated between the BDNF 11757 G/C and Val66Met polymorphisms and a global haplotype estimate of four BDNF polymorphisms and the posterior superior cerebellar vermis volume in the controls as well as in the combined group, but not in the patients. The 11757 G/C polymorphism was associated with cerebellar hemisphere white and gray matter volumes in the combined group. The BDNF -633 T/A polymorphism was associated with gray matter of the putamen in the controls. Trends for associations between several polymorphisms/haplotype estimates and MRI volumes were found. BDNF gene variation may influence brain morphology. The effects may be different in patients with schizophrenia and healthy subjects.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 55%

Section: Previously Reported Brain Abnormalities In the Current Subjementioning

confidence: 73%

Section: Scan Post Processingmentioning

confidence: 99%

See 2 more Smart Citations

BDNF gene variants and brain morphology in schizophrenia

Agartz

Sedvall

Terenius

et al. 2006

American J of Med Genetics Pt B

Self Cite

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“…Ten healthy control subjects also underwent MRI. The schizophrenic patients had reduced volumes of grey and white matter in the caudate nucleus compared to the healthy con-Okugawa/Nobuhara/Takase/Saito/ Yoshimura/Kinoshita Neuropsychobiology 2007;55: [43][44][45][46] 44 et al [2] reported that schizophrenic patients had a reduced white matter volume in the caudate nucleus compared to healthy subjects. An increased volume of the caudate nucleus was found in patients with first-episode schizophrenia [3] .…”

Section: Introductionmentioning

confidence: 99%

Olanzapine Increases Grey and White Matter Volumes in the Caudate Nucleus of Patients with Schizophrenia

et al. 2007

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There are inconsistent reports regarding the caudate nucleus volume in patients with schizophrenia compared with healthy subjects. The reason for this is that neuroleptic medication may affect the volume of the caudate nucleus in schizophrenic patients. To clarify which antipsychotic medication changes the volume of the caudate nucleus in patients with schizophrenia, we measured the volumes of grey and white matter in the caudate nucleus of schizophrenic patients. Ten patients with schizophrenia were examined twice by magnetic resonance imaging (MRI) to measure the grey and white matter volumes in the caudate nucleus. After the first MRI examination, all the patients were treated with olanzapine. The clinical responses were evaluated by the positive and negative rating scale. When the symptoms improved, the patients were examined by a second MRI scan. Ten healthy control subjects also underwent MRI. The schizophrenic patients had reduced volumes of grey and white matter in the caudate nucleus compared to the healthy control subjects. The volumes of grey and white matter in the caudate nucleus of the schizophrenic patients increased after treatment with olanzapine. These findings suggest that treatment with olanzapine may increase the grey and white matter volumes in the caudate nucleus in patients with schizophrenia.

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Towards understanding the schizophrenia code: An expanded convergent functional genomics approach

Le-Niculescu

Balaraman

Patel

et al. 2007

American J of Med Genetics Pt B

129

124

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Identifying genes for schizophrenia through classical genetic approaches has proven arduous. Here, we present a comprehensive convergent analysis that translationally integrates brain gene expression data from a relevant pharmacogenomic mouse model (involving treatments with a psychomimetic agent - phencyclidine (PCP), and an anti-psychotic - clozapine), with human genetic linkage data and human postmortem brain data, as a Bayesian strategy of cross validating findings. Topping the list of candidate genes, we have three genes involved in GABA neurotransmission (GABRA1, GABBR1, and GAD2), one gene involved in glutamate neurotransmission (GRIA2), one gene involved in neuropeptide signaling (TAC1), two genes involved in synaptic function (SYN2 and KCNJ4), six genes involved in myelin/glial function (CNP, MAL, MBP, PLP1, MOBP and GFAP), and one gene involved in lipid metabolism (LPL). These data suggest that schizophrenia is primarily a disorder of brain functional and structural connectivity, with GABA neurotransmission playing a prominent role. These findings may explain the EEG gamma band abnormalities detected in schizophrenia. The analysis also revealed other high probability candidates genes (neurotransmitter signaling, other structural proteins, ion channels, signal transduction, regulatory enzymes, neuronal migration/neurite outgrowth, clock genes, transcription factors, RNA regulatory genes), pathways and mechanisms of likely importance in pathophysiology. Some of the pathways identified suggest possible avenues for augmentation pharmacotherapy of schizophrenia with other existing agents, such as benzodiazepines, anticonvulsants and lipid modulating agents. Other pathways are new potential targets for drug development. Lastly, a comparison with our earlier work on bipolar disorder illuminates the significant molecular overlap between schizophrenia and bipolar disorder.

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Altered White Matter/Gray Matter Proportions in the Striatum of Patients With Schizophrenia: A Volumetric MRI Study

Abstract: The proportion of white matter to gray matter tissue volumes of the caudate, putamen, and nucleus accumbens is altered in medicated chronic schizophrenia patients, but the total volumes are unchanged.

Cited by 52 publications

References 36 publications

BDNF gene variants and brain morphology in schizophrenia

BDNF gene variants and brain morphology in schizophrenia

Olanzapine Increases Grey and White Matter Volumes in the Caudate Nucleus of Patients with Schizophrenia

Towards understanding the schizophrenia code: An expanded convergent functional genomics approach

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