Heritability of Memory Functions and Related Brain Volumes: A Schizophrenia Spectrum Study of 214 Twins

Author:

Lemvigh Cecilie K123ORCID,Brouwer Rachel M4ORCID,Sahakian Barbara J56,Robbins Trevor W67ORCID,Johansen Louise B1ORCID,Legind Christian S1ORCID,Anhøj Simon J1ORCID,Hilker Rikke18,Hulshoff Pol Hilleke E4ORCID,Ebdrup Bjørn H138ORCID,Pantelis Christos3ORCID,Glenthøj Birte Y18ORCID,Fagerlund Birgitte12ORCID

Affiliation:

1. Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Glostrup, Denmark

2. Department of Psychology, Faculty of Social Sciences, University of Copenhagen, Copenhagen, Denmark

3. Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia

4. Department of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

5. Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK

6. Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK

7. Department of Psychology, University of Cambridge, Cambridge, UK

8. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Abstract

Abstract Background Memory performance is heritable and shares partial genetic etiology with schizophrenia. How the genetic overlap between memory and schizophrenia is related to intelligence (IQ) and brain volumes has not been formally tested using twin modeling. Methods A total of 214 twins were recruited nationwide by utilization of the Danish registers, including monozygotic and dizygotic twin pairs concordant or discordant for a schizophrenia spectrum disorder and healthy control pairs. Memory/IQ assessments and MRI scans were performed and structural equation modeling was applied to examine the genetic and environmental effects and to quantify associations with schizophrenia liability. Results Significant heritability estimates were found for verbal, visual and working memory. Verbal and visual memory were associated with schizophrenia, and for visual memory the association was due to overlapping genetics. IQ was highly heritable, but only performance IQ was associated with schizophrenia. Genetic factors also contributed to total brain, right superior frontal, left rostral middle frontal and hippocampal volumes. Smaller total brain and hippocampal volumes were associated with schizophrenia, and for the left hippocampus this association was due to overlapping genetic factors. All 3 memory measures were associated with IQ, but only visual memory was associated with total brain and hippocampal volumes. Discussion Specific memory measures and brain volumes were moderately heritable and showed overlap with schizophrenia liability, suggesting partially shared etiological influences. Our findings further suggest that factors impacting IQ also influence memory, whereas memory impairments and brain volume abnormalities appear to represent separate pathological processes in the pathway to schizophrenia.

Funder

Lundbeck Foundation

The Mental Health Services, Capital Region of Denmark

NHMRC Senior Principal Research Fellowship

Publisher

Oxford University Press (OUP)

Subject

Psychiatry and Mental health

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