Reduced Dorsal and Orbital Prefrontal Gray Matter Volumes in Schizophrenia

Gur, Raquel E.; Cowell, Patricia E.; Latshaw, Amanda; Turetsky, Bruce I.; Grossman, Robert I.; Arnold, Steven E.; Bilker, Warren B.; Gur, Ruben C.

doi:10.1001/archpsyc.57.8.761

Cited by 346 publications

(224 citation statements)

References 74 publications

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“…They reported that the white matter reduction was most severe in the orbitofrontal region. Gur et al (2000) reported an association, in women schizophrenic subjects only, between decreased orbital (gray matter) volumes and negative symptoms. In the current sample, we also found a significant correlation between total SANS scores and left frontal gray matter volume in schizophrenic subjects.…”

Section: Discussionmentioning

confidence: 99%

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

Wible

Anderson

Shenton

et al. 2001

Psychiatry Research: Neuroimaging

185

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The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial-temporal lobe regions -two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal-prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.

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Section: Discussionmentioning

confidence: 99%

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

Wible

Anderson

Shenton

et al. 2001

Psychiatry Research: Neuroimaging

185

100

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“…Indeed abnormalities in prefrontal metabolism and impairment in executive function have been documented in a wide range of disorders including those with dopaminergic involvement such as drug addiction, schizophrenia, Parkinson's disease and ADHD (Volkow et al, 1993b;Gur et al, 2000;Robbins, 2007;Zgaljardic et al, 2006).…”

Section: Study Limitationsmentioning

confidence: 99%

Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors

et al. 2008

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Dopamine's role in inhibitory control is well recognized and its disruption may contribute to behavioral disorders of discontrol such as obesity. However, the mechanism by which impaired dopamine neurotransmission interferes with inhibitory control is poorly understood. We had previously documented a reduction in dopamine D2 receptors in morbidly obese subjects. To assess if the reductions in dopamine D2 receptors were associated with activity in prefrontal brain regions implicated in inhibitory control we assessed the relationship between dopamine D2 receptor availability in striatum with brain glucose metabolism (marker of brain function) in ten morbidly obese subjects (BMI>40 kg/m 2 ) and compared it to that in twelve non-obese controls. PET was used with [ 11 C]raclopride to assess D2 receptors and with [ 18 F] FDG to assess regional brain glucose metabolism. In obese subjects striatal D2 receptor availability was lower than controls and was positively correlated with metabolism in dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus and somatosensory cortices. In controls correlations with prefrontal metabolism were not significant but comparisons with those in obese subjects were not significant, which does not permit to ascribe the associations as unique to obesity. The associations between striatal D2 receptors and prefrontal metabolism in obese subjects suggest that decreases in striatal D2 receptors could contribute to overeating via their modulation of striatal prefrontal pathways, which participate in inhibitory control and salience attribution. The association between striatal D2 receptors and metabolism in somatosensory cortices (regions that process palatability) could underlie one of the mechanisms through which dopamine regulates the reinforcing properties of food. KeywordsOrbitofrontal cortex; Cingulate gyrus; Dorsolateral prefrontal; Dopamine transporters; Raclopride, PET The increase in obesity and associated metabolic diseases seen over the past decade has raised concern that if not controlled this may become the number one preventable public health threat for the 21st century (Sturm, 2002 (Berthoud, 2007). The extent to which individuals differ in their ability to inhibit these responses and control how much they eat is likely to modulate their risk for overeating in our current food rich environments (Berthoud, 2007).We had shown that in healthy individuals D2 receptor availability in the striatum modulated eating behavioral patterns (Volkow et al., 2003). Specifically the tendency to eat when exposed to negative emotions was negatively correlated with D2 receptor availability (the lower the D2 receptors the higher the likelihood that an individual would eat if emotionally stressed). In addition, in a different study, we showed that morbidly obese subjects (BMI>40) had lower than normal D2 receptor availability and these reductions were proportional to their BMI (Wang et al., 2001). These findings led us to postulate that low D2 receptor availability could put an...

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“…The sample overlaps with samples reported in earlier publications (18)(19)(20). The current dataset includes all SCZ patients, their family members, and demographically balanced HC who have been studied on the same scanner with the same protocol and who had suitable quality of scan for automated analysis of the entire supertentorial brain.…”

Section: Participantsmentioning

confidence: 99%

Unaffected Family Members and Schizophrenia Patients Share Brain Structure Patterns: A High-Dimensional Pattern Classification Study

Fan

Gur²,

Gur³

et al. 2008

Biological Psychiatry

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Background-A number of studies have provided evidence for genetic modulation of brain structure in unaffected family members of schizophrenia patients (FM), using conventional regionof-interest volumetric analysis. High-dimensional pattern analysis and classification methods have been reported recently to have the capacity to determine subtle and spatially complex structural patterns that distinguish schizophrenia patients from healthy controls, using standard magnetic resonance imaging (MRI). This study investigates whether such endophenotypic patterns are found in FM via similar computer-based image analysis approaches.Correspond to: Christos Davatzikos, Professor, Department of Radiology, University of Pennsylvania, 3600 Market street, Suite 380, Philadelphia, PA 19104, Tel: 215-349-8587, Fax: 215-614-0266, E-Mail: christos@rad.upenn.edu. Financial Disclosures: There are no conflicts of interest including any financial, personal or other relationships with people or organizations, by any of the co-authors, related to the work described in the paper.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMethods-A high-dimensional pattern classifier was constructed from a group of 69 patients and 79 healthy controls, via an analysis that identified a subtle, and spatially complex and distributed pattern of reduced brain volumes. Patients were distinguished from healthy controls with sensitivity of 92.9% and specificity 89.8%, using jackknife method. Then the constructed classifier was applied to examine brain structure of 30 FM.Results-The classifier indicated that family members had structural profiles highly overlapping with those of patients. Moreover, an orbitofrontal region of relatively increased white matter was found to contribute significantly to the classification, indicating that white matter alterations, along with reductions of gray matter volumes, might be present in patients and unaffected family members.Conclusions-These findings give evidence that high-dimensional pattern analysis and classification can identify complex and subtle structural endophenotypes that are shared by probands and their unaffected family members.

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Reduced Dorsal and Orbital Prefrontal Gray Matter Volumes in Schizophrenia

Cited by 346 publications

References 74 publications

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors

Unaffected Family Members and Schizophrenia Patients Share Brain Structure Patterns: A High-Dimensional Pattern Classification Study

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