ArticleMolecular psychiatry2015
Reciprocal causation models of cognitive vs volumetric cerebral intermediate phenotypes for schizophrenia in a pan-European twin cohort.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 3 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder.Human brain mapping · 2022Pooled it
- Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.Schizophrenia bulletin · 2017Pooled it
- Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.Nature neuroscience · 2016Pooled it
- Cardiometabolic Biomarkers at Age 44-45 in the Psychosis Spectrum: The British National Child Development Study.Schizophrenia bulletin · 2026Article
- Causal associations between schizophrenia and other psychiatric disorders: A Mendelian randomization study.The Journal of international medical research · 2025Article
- Psychosis superspectrum I: Nosology, etiology, and lifespan development.Molecular psychiatry · 2024Review
- The Risk for Schizophrenia-Bipolar Spectrum: Does the Apple Fall Close to the Tree? A Narrative Review.International journal of environmental research and public health · 2023Review
- Neurodevelopmental disturbances in schizophrenia: evidence from genetic and environmental factors.Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- Reciprocal causation mixture model for robust Mendelian randomization analysis using genome-scale summary data.Nature communications · 2023Article
- Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia.Frontiers in cellular neuroscience · 2023Review
- Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology.International journal of molecular sciences · 2021Review
- Cortical Gyrification, Psychotic-Like Experiences, and Cognitive Performance in Nonclinical Subjects.Schizophrenia bulletin · 2020Article
- Unraveling the Relation Between Reading Comprehension and Print Exposure.Child development · 2020Article
- Running in the Family? Structural Brain Abnormalities and IQ in Offspring, Siblings, Parents, and Co-twins of Patients with Schizophrenia.Schizophrenia bulletin · 2019Article
- Inheritance of Neural Substrates for Motivation and Pleasure.Psychological science · 2019Article
- Polygenic risk score increases schizophrenia liability through cognition-relevant pathways.Brain : a journal of neurology · 2019Article
- Article
- Using genetic data to strengthen causal inference in observational research.Nature reviews. Genetics · 2018Review
- A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2018Article
- 30 Years on: How the Neurodevelopmental Hypothesis of Schizophrenia Morphed Into the Developmental Risk Factor Model of Psychosis.Schizophrenia bulletin · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 6 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In aetiologically complex illnesses such as schizophrenia, there is no direct link between genotype and phenotype. Intermediate phenotypes could help clarify the underlying biology and assist in the hunt for genetic vulnerability variants. We have previously shown that cognition shares substantial genetic variance with schizophrenia; however, it is unknown if this reflects pleiotropic effects, direct causality or some shared third factor that links both, for example, brain volume (BV) changes. We quantified the degree of net genetic overlap and tested the direction of causation between schizophrenia liability, brain structure and cognition in a pan-European schizophrenia twin cohort consisting of 1243 members from 626 pairs. Cognitive deficits lie upstream of the liability for schizophrenia with about a quarter of the variance in liability to schizophrenia explained by variation in cognitive function. BV changes lay downstream of schizophrenia liability, with 4% of BV variation explained directly by variation in liability. However, our power to determine the nature of the relationship between BV deviation and schizophrenia liability was more limited. Thus, while there was strong evidence that cognitive impairment is causal to schizophrenia liability, we are not in a position to make a similar statement about the relationship between liability and BV. This is the first study to demonstrate that schizophrenia liability is expressed partially through cognitive deficits. One prediction of the finding that BV changes lie downstream of the disease liability is that the risk loci that influence schizophrenia liability will thereafter influence BV and to a lesser extent. By way of contrast, cognitive function lies upstream of schizophrenia, thus the relevant loci will actually have a larger effect size on cognitive function than on schizophrenia. These are testable predictions.
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