Hippocampal Volumes in Schizophrenic Twins

Erp, Theo G.M. van; Saleh, Peter A.; Huttunen, Matti; Lönnqvist, Jouko; Kaprio, Jaakko; Salonen, Oili; Valanne, Leena; Poutanen, Veli-Pekka; Standertskjöld-Nordenstam, Carl-Gustav; Cannon, Tyrone D.

doi:10.1001/archpsyc.61.4.346

Cited by 132 publications

(67 citation statements)

References 47 publications

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“…However, shared environmental factors could nonetheless have a nonnegligible contribution to abnormalities observed within particular cerebral structures. Using variance components analysis, hippocampal volume was in fact found to be substantially influenced by unique and shared environmental factors in schizophrenia subjects and their nonpsychotic twins, whereas additive genetic effects dominated in healthy twin pairs (van Erp et al, 2004). We are not aware of any twin studies that have used similar analytic techniques in the thalamus.…”

Section: Discussionmentioning

confidence: 99%

Thalamic Shape Abnormalities in Individuals with Schizophrenia and Their Nonpsychotic Siblings

Harms

Wang²,

Mamah³

et al. 2007

J. Neurosci.

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Deficits in the volume of the thalamus have been observed in both individuals with schizophrenia and their nonpsychotic relatives. However, no studies to date have examined the underlying pattern of thalamic shape change in relatives of individuals with schizophrenia. This study examined the volume and shape of the thalamus in schizophrenia subjects, their siblings, and healthy control individuals. T1-weighted magnetic resonance scans were collected in a group of young subjects with schizophrenia (mean age, 23 years) and their nonpsychotic siblings (n ϭ 25 pairs), and control subjects and their siblings (n ϭ 40 pairs). Thalamic surfaces were generated using high-dimensional brain mapping. A canonical weighting function was derived from the contrast between schizophrenia and control subjects and then used to generate a canonical shape score for all subjects. Maps of the estimated surface displacement between groups were also created to visualize the thalamic shape differences between groups. The thalamic canonical scores of the siblings of the schizophrenia probands were intermediate between the probands and healthy control subjects. These siblings also displayed an intermediate degree of the inward surface deformation of the anterior and posterior thalamus that was present between schizophrenia probands and controls. There was no main effect of group status on thalamic volume and no significant correlations of the structural measures with measures of psychopathology or cognitive function. Our results indicate that thalamic shape abnormalities are present in relatively young individuals with schizophrenia and their siblings. Inward deformation of the anterior and posterior regions of the thalamus represents a potential neuroanatomical endophenotype of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Thalamic Shape Abnormalities in Individuals with Schizophrenia and Their Nonpsychotic Siblings

Harms

Wang²,

Mamah³

et al. 2007

J. Neurosci.

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“…Magnetic resonance imaging (MRI) studies in unaffected family members (FM) of schizophrenia patients suggest that genetic factors affect brain structure (1)(2)(3)(4)(5), with FM generally showing characteristics of brain structure in-between patients and healthy controls (HC). Likewise, high risk individuals such as patient offsprings with no clinical history of psychosis, have similar structural abnormalities, most notably in hippocampus and amygdala, with some contradictory results (6-9) having being reported in the literature.…”

Section: Introductionmentioning

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

111

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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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“…This study also reported that both MZ and DZ discordant twins have smaller whole-brain, parahippocampal, and hippocampal volumes than healthy twins, and that affected twins have yet smaller whole-brain volumes than their non-schizophrenic co-twins. The hippocampal size findings were replicated in a Finnish twin study [van Erp et al, 2004]. Together, these observations indicate the presence of a genetic influence on brain volumes, but the additional reduction in whole-brain volume observed in the affected compared to the unaffected co-twins dynamic interaction between DNA sequence, epigenetic DNA modifications, environment, gene expression, and environmental factors that all combine to influence phenotype.…”

Section: Classical Twin Study Designs: Genes and Environmentmentioning

confidence: 68%

Not really identical: Epigenetic differences in monozygotic twins and implications for twin studies in psychiatry

Haque

Gottesman

Wong

2009

American J of Med Genetics Pt C

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Classical twin studies in the field of psychiatry generally fall into one of two categories: (1) those designed to identify environmental risk factors causing discordance in monozygotic (MZ) twins and (2) those geared towards identifying genetic risk factors. However, neither environment nor differences in DNA sequence can fully account for phenotypic discordance among MZ twins. The field of epigenetics -DNA modifications that can affect gene expression -offers new models to understand discordance in MZ twins. In the past, MZ twins were regarded as genetically-identical controls for differing environmental conditions. In contrast, the evolving current concept is that epigenetic differences between MZ twins may modulate differences in diverse phenotype, from disease to personality. In this article, we review some twin studies, and discuss the dynamic interactions between stochastic, environmental, and epigenetic variables that influence neurobiological phenotypes. ß

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Hippocampal Volumes in Schizophrenic Twins

Cited by 132 publications

References 47 publications

Thalamic Shape Abnormalities in Individuals with Schizophrenia and Their Nonpsychotic Siblings

Thalamic Shape Abnormalities in Individuals with Schizophrenia and Their Nonpsychotic Siblings

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

Not really identical: Epigenetic differences in monozygotic twins and implications for twin studies in psychiatry

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