Overlapping and Segregating Structural Brain Abnormalities in Twins With Schizophrenia or Bipolar Disorder

Hilleke E. Hulshoff Pol; G. Caroline M. van Baal; Hugo G. Schnack; Rachel G. H. Brans; Astrid C. van der Schot; Rachel M. Brouwer; Neeltje E. M. van Haren; Claude Lepage; D. Louis Collins; Alan C. Evans; Dorret I. Boomsma; Willem Nolen; Rene S. Kahn

Overlapping and Segregating Structural Brain Abnormalities in Twins With Schizophrenia or Bipolar Disorder

Hilleke E. Hulshoff Pol^*, G. Caroline M. van Baal, Hugo G. Schnack, Rachel G. H. Brans, Astrid C. van der Schot, Rachel M. Brouwer, Neeltje E. M. van Haren, Claude Lepage, D. Louis Collins, Alan C. Evans, Dorret I. Boomsma, Willem Nolen, Rene S. Kahn

^*Corresponding author for this work

Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)

Research output: Contribution to journal › Article › Academic › peer-review

102 Citations (Scopus)

Abstract

Context: The nosologic dichotomy between schizophrenia and bipolar disorder (BD) as formulated by Kraepelin is currently being questioned, stimulated by the finding that schizophrenia and BD partly share a common genetic origin. Although both disorders are characterized by changes in brain structure, family studies suggest more segregating than overlapping neuroanatomical abnormalities in both disorders.

Objectives: To investigate whether patients with schizophrenia and patients with BD display overlapping abnormalities in brain volumes and cortical thickness and whether these are caused by shared genetic or environmental influences.

Design: Magnetic resonance imaging findings of monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia, twin pairs concordant and discordant for BD, and healthy twin pairs were compared using structural equation modeling.

Setting: The Netherlands Twin Register and University Medical Center Utrecht.

Participants: A total of 310 individuals from 158 (152 complete and 6 incomplete) twin pairs were included: 26 pairs discordant for schizophrenia (13 MZ and 13 DZ), 49 pairs with BD (9 MZ and 4 DZ concordant; 14 MZ and 22 DZ discordant), and 83 healthy twin pairs (44 MZ and 39 DZ).

Main Outcome Measures: Estimates of additive genetic and unique environmental associations between schizophrenia and BD with overlapping and nonoverlapping volumes and cortical thickness.

Results: Higher genetic liabilities for schizophrenia and BD were associated with smaller white matter volume, thinner right (and left) parahippocampus, thinner right orbitofrontal cortex, and thicker temporoparietal and left superior motor cortices; higher environmental liabilities were associated with thinner right medial occipital cortex. Genetic liability for schizophrenia was associated with thicker right parietal cortex; for BD, with larger intracranial volume.

Conclusions: Brain structures reflect overlapping and segregating genetic liabilities for schizophrenia and BD. The overlapping smaller white matter volume and common areas of thinner cortex suggest that both disorders share genetic (neurodevelopmental) roots.

Original language	English
Pages (from-to)	349-359
Number of pages	11
Journal	Archives of General Psychiatry
Volume	69
Issue number	4
Publication status	Published - Apr-2012

Keywords

CHILDHOOD-ONSET SCHIZOPHRENIA
MATTER VOLUME ABNORMALITIES
MENTAL-HEALTH SURVEY
WHITE-MATTER
CORTICAL THICKNESS
UNAFFECTED RELATIVES
GENERAL-POPULATION
CEREBRAL-CORTEX
1ST EPISODE
MR-IMAGES

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Pol, H. E. H., van Baal, G. C. M., Schnack, H. G., Brans, R. G. H., van der Schot, A. C., Brouwer, R. M., van Haren, N. E. M., Lepage, C., Collins, D. L., Evans, A. C., Boomsma, D. I., Nolen, W., & Kahn, R. S. (2012). Overlapping and Segregating Structural Brain Abnormalities in Twins With Schizophrenia or Bipolar Disorder. Archives of General Psychiatry, 69(4), 349-359.

@article{6c5e6d0b67b3400a86783a4883aace4a,

title = "Overlapping and Segregating Structural Brain Abnormalities in Twins With Schizophrenia or Bipolar Disorder",

abstract = "Context: The nosologic dichotomy between schizophrenia and bipolar disorder (BD) as formulated by Kraepelin is currently being questioned, stimulated by the finding that schizophrenia and BD partly share a common genetic origin. Although both disorders are characterized by changes in brain structure, family studies suggest more segregating than overlapping neuroanatomical abnormalities in both disorders.Objectives: To investigate whether patients with schizophrenia and patients with BD display overlapping abnormalities in brain volumes and cortical thickness and whether these are caused by shared genetic or environmental influences.Design: Magnetic resonance imaging findings of monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia, twin pairs concordant and discordant for BD, and healthy twin pairs were compared using structural equation modeling.Setting: The Netherlands Twin Register and University Medical Center Utrecht.Participants: A total of 310 individuals from 158 (152 complete and 6 incomplete) twin pairs were included: 26 pairs discordant for schizophrenia (13 MZ and 13 DZ), 49 pairs with BD (9 MZ and 4 DZ concordant; 14 MZ and 22 DZ discordant), and 83 healthy twin pairs (44 MZ and 39 DZ).Main Outcome Measures: Estimates of additive genetic and unique environmental associations between schizophrenia and BD with overlapping and nonoverlapping volumes and cortical thickness.Results: Higher genetic liabilities for schizophrenia and BD were associated with smaller white matter volume, thinner right (and left) parahippocampus, thinner right orbitofrontal cortex, and thicker temporoparietal and left superior motor cortices; higher environmental liabilities were associated with thinner right medial occipital cortex. Genetic liability for schizophrenia was associated with thicker right parietal cortex; for BD, with larger intracranial volume.Conclusions: Brain structures reflect overlapping and segregating genetic liabilities for schizophrenia and BD. The overlapping smaller white matter volume and common areas of thinner cortex suggest that both disorders share genetic (neurodevelopmental) roots.",

keywords = "CHILDHOOD-ONSET SCHIZOPHRENIA, MATTER VOLUME ABNORMALITIES, MENTAL-HEALTH SURVEY, WHITE-MATTER, CORTICAL THICKNESS, UNAFFECTED RELATIVES, GENERAL-POPULATION, CEREBRAL-CORTEX, 1ST EPISODE, MR-IMAGES",

author = "Pol, {Hilleke E. Hulshoff} and {van Baal}, {G. Caroline M.} and Schnack, {Hugo G.} and Brans, {Rachel G. H.} and {van der Schot}, {Astrid C.} and Brouwer, {Rachel M.} and {van Haren}, {Neeltje E. M.} and Claude Lepage and Collins, {D. Louis} and Evans, {Alan C.} and Boomsma, {Dorret I.} and Willem Nolen and Kahn, {Rene S.}",

year = "2012",

month = apr,

language = "English",

volume = "69",

pages = "349--359",

journal = "Archives of General Psychiatry",

issn = "0003-990X",

publisher = "AMER MEDICAL ASSOC",

number = "4",

}

TY - JOUR

T1 - Overlapping and Segregating Structural Brain Abnormalities in Twins With Schizophrenia or Bipolar Disorder

AU - Pol, Hilleke E. Hulshoff

AU - van Baal, G. Caroline M.

AU - Schnack, Hugo G.

AU - Brans, Rachel G. H.

AU - van der Schot, Astrid C.

AU - Brouwer, Rachel M.

AU - van Haren, Neeltje E. M.

AU - Lepage, Claude

AU - Collins, D. Louis

AU - Evans, Alan C.

AU - Boomsma, Dorret I.

AU - Nolen, Willem

AU - Kahn, Rene S.

PY - 2012/4

Y1 - 2012/4

N2 - Context: The nosologic dichotomy between schizophrenia and bipolar disorder (BD) as formulated by Kraepelin is currently being questioned, stimulated by the finding that schizophrenia and BD partly share a common genetic origin. Although both disorders are characterized by changes in brain structure, family studies suggest more segregating than overlapping neuroanatomical abnormalities in both disorders.Objectives: To investigate whether patients with schizophrenia and patients with BD display overlapping abnormalities in brain volumes and cortical thickness and whether these are caused by shared genetic or environmental influences.Design: Magnetic resonance imaging findings of monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia, twin pairs concordant and discordant for BD, and healthy twin pairs were compared using structural equation modeling.Setting: The Netherlands Twin Register and University Medical Center Utrecht.Participants: A total of 310 individuals from 158 (152 complete and 6 incomplete) twin pairs were included: 26 pairs discordant for schizophrenia (13 MZ and 13 DZ), 49 pairs with BD (9 MZ and 4 DZ concordant; 14 MZ and 22 DZ discordant), and 83 healthy twin pairs (44 MZ and 39 DZ).Main Outcome Measures: Estimates of additive genetic and unique environmental associations between schizophrenia and BD with overlapping and nonoverlapping volumes and cortical thickness.Results: Higher genetic liabilities for schizophrenia and BD were associated with smaller white matter volume, thinner right (and left) parahippocampus, thinner right orbitofrontal cortex, and thicker temporoparietal and left superior motor cortices; higher environmental liabilities were associated with thinner right medial occipital cortex. Genetic liability for schizophrenia was associated with thicker right parietal cortex; for BD, with larger intracranial volume.Conclusions: Brain structures reflect overlapping and segregating genetic liabilities for schizophrenia and BD. The overlapping smaller white matter volume and common areas of thinner cortex suggest that both disorders share genetic (neurodevelopmental) roots.

AB - Context: The nosologic dichotomy between schizophrenia and bipolar disorder (BD) as formulated by Kraepelin is currently being questioned, stimulated by the finding that schizophrenia and BD partly share a common genetic origin. Although both disorders are characterized by changes in brain structure, family studies suggest more segregating than overlapping neuroanatomical abnormalities in both disorders.Objectives: To investigate whether patients with schizophrenia and patients with BD display overlapping abnormalities in brain volumes and cortical thickness and whether these are caused by shared genetic or environmental influences.Design: Magnetic resonance imaging findings of monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia, twin pairs concordant and discordant for BD, and healthy twin pairs were compared using structural equation modeling.Setting: The Netherlands Twin Register and University Medical Center Utrecht.Participants: A total of 310 individuals from 158 (152 complete and 6 incomplete) twin pairs were included: 26 pairs discordant for schizophrenia (13 MZ and 13 DZ), 49 pairs with BD (9 MZ and 4 DZ concordant; 14 MZ and 22 DZ discordant), and 83 healthy twin pairs (44 MZ and 39 DZ).Main Outcome Measures: Estimates of additive genetic and unique environmental associations between schizophrenia and BD with overlapping and nonoverlapping volumes and cortical thickness.Results: Higher genetic liabilities for schizophrenia and BD were associated with smaller white matter volume, thinner right (and left) parahippocampus, thinner right orbitofrontal cortex, and thicker temporoparietal and left superior motor cortices; higher environmental liabilities were associated with thinner right medial occipital cortex. Genetic liability for schizophrenia was associated with thicker right parietal cortex; for BD, with larger intracranial volume.Conclusions: Brain structures reflect overlapping and segregating genetic liabilities for schizophrenia and BD. The overlapping smaller white matter volume and common areas of thinner cortex suggest that both disorders share genetic (neurodevelopmental) roots.

KW - CHILDHOOD-ONSET SCHIZOPHRENIA

KW - MATTER VOLUME ABNORMALITIES

KW - MENTAL-HEALTH SURVEY

KW - WHITE-MATTER

KW - CORTICAL THICKNESS

KW - UNAFFECTED RELATIVES

KW - GENERAL-POPULATION

KW - CEREBRAL-CORTEX

KW - 1ST EPISODE

KW - MR-IMAGES

M3 - Article

SN - 0003-990X

VL - 69

SP - 349

EP - 359

JO - Archives of General Psychiatry

JF - Archives of General Psychiatry

IS - 4

ER -

Overlapping and Segregating Structural Brain Abnormalities in Twins With Schizophrenia or Bipolar Disorder

Abstract

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