Decreased left amygdala and hippocampal volumes in young offspring at risk for schizophrenia

Keshavan, Matcheri S.; Dick, Elizabeth L.; Mankowski, I.; Harenski, Keith A.; Montrose, Debra M.; Diwadkar, Vaibhav A.; DeBellis, Michael

doi:10.1016/s0920-9964(01)00404-2

Cited by 123 publications

(89 citation statements)

References 69 publications

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“…Significant differences were found between FM and HC, and SCZ and HC. A significant difference was found between SCZ and FM, which however becomes marginal after correction for multiple (6) comparisons at the p=0.05 level, and insignificant at the p=0.01 level.…”

Section: Whole-brain Voxel-based Volumetric Analysismentioning

confidence: 77%

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

Fan

Gur²,

Gur³

et al. 2008

Biological Psychiatry

112

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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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Section: Whole-brain Voxel-based Volumetric Analysismentioning

confidence: 77%

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

Fan

Gur²,

Gur³

et al. 2008

Biological Psychiatry

112

View full text Add to dashboard Cite

show abstract

“…In individuals at high risk for developing schizophrenia, researchers have found smaller bilateral hippocampi, 298,299 as well as no significant hippocampal volumetric changes. 300 A study comparing schizophrenia patients with subjects at high risk for developing schizophrenia and controls, found that the left amygdala-hippocampal complex was smaller in FE schizophrenia than in the high-risk…”

Section: Schizophreniamentioning

confidence: 99%

MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders

2004

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Magnetic resonance imaging (MRI) has opened a new window to the brain. Measuring hippocampal volume with MRI has provided important information about several neuropsychiatric disorders. We reviewed the literature and selected all English-language, human subject, data-driven papers on hippocampal volumetry, yielding a database of 423 records. Smaller hippocampal volumes have been reported in epilepsy, Alzheimer's disease, dementia, mild cognitive impairment, the aged, traumatic brain injury, cardiac arrest, Parkinson's disease, Huntington's disease, Cushing's disease, herpes simplex encephalitis, Turner's syndrome, Down's syndrome, survivors of low birth weight, schizophrenia, major depression, posttraumatic stress disorder, chronic alcoholism, borderline personality disorder, obsessive-compulsive disorder, and antisocial personality disorder. Significantly larger hippocampal volumes have been correlated with autism and children with fragile X syndrome. Preservation of hippocampal volume has been reported in congenital hyperplasia, children with fetal alcohol syndrome, anorexia nervosa, attention-deficit and hyperactivity disorder, bipolar disorder, and panic disorder. Possible mechanisms of hippocampal volume loss in neuropsychiatric disorders are discussed.

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“…Since it is difficult to differentiate between amygdala and hippocampus complex (Shenton et al, 2001(Shenton et al, , 2002, we used the method described by Keshavan et al (2002) which uses the anterior wall of mammillary bodies as the first slice and slice no. 78 (or the slice where the superior and inferior colliculi are fused) as the last slice to measure the hippocampus.…”

Section: Structural Mri Volumetric Analysismentioning

confidence: 99%

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

Brown

Wolfshohl

Shad

et al. 2007

Neuropsychopharmacol

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An extensive animal literature suggests that excessive corticosteroid exposure is associated with changes in memory and the hippocampus. Agents that decrease glutamate attenuate corticosteroid effects on the hippocampus. Minimal data are available on preventing or reversing corticosteroid effects on the human hippocampus. We previously reported that open-label lamotrigine was associated with significant improvement in declarative memory in corticosteroid-treated patients. We now examine the impact of 24 weeks of randomized, placebo-controlled lamotrigine therapy on declarative memory (primary aim) and hippocampal volume (secondary aim) in 28 patients (n ¼ 16 for lamotrigine, n ¼ 12 for placebo) taking prescription corticosteroids. All participants with data from at least one postbaseline assessment (n ¼ 9 for lamotrigine, n ¼ 11 for placebo) were included in the analysis. Declarative memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT) at baseline and weeks 12 and 24. Hippocampal and total brain volumes were manually traced from MRI scans obtained at baseline and week 24. On the basis of an ANCOVA analysis, total words learned on the RAVLT at exit were significantly greater in the lamotrigine group (n ¼ 8, missing data or dropouts n ¼ 8) compared to the placebo group (n ¼ 11, dropout n ¼ 1). RAVLT scores in the lamotrigine group increased from mildly impaired to average range. Hippocampal volume changes were small in both lamotrigine (n ¼ 7) and placebo (n ¼ 7) groups during the 24-week assessment period and between-group differences were not significant. Results suggest that lamotrigine may improve declarative memory in patients taking prescription corticosteroids although differential dropout rate in the two groups is a concern.

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Decreased left amygdala and hippocampal volumes in young offspring at risk for schizophrenia

Cited by 123 publications

References 69 publications

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

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

MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

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