Genetic and non-genetic vulnerability factors in schizophrenia: the basis of the “Two hit hypothesis.”

Bayer, Thomas A; Falkai, Peter; Maier, Wolfgang

doi:10.1016/s0022-3956(99)00039-4

Cited by 346Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorMental Health and Psychiatry

Genetic and non-genetic vulnerability factors in schizophrenia: the basis of the “Two hit hypothesis.”

Bayer, Thomas A, Falkai, Peter, Maier, Wolfgang·1999·Journal of Psychiatric Research

DOI 10.1016/s0022-3956(99)00039-4

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The classical vulnerability-stress model and conceptually similar approaches such as the 'allostatic load', 'double-hit' or 'three-hit' hypotheses predominantly focus on risk-increasing factors that, assuming a cumulative effect, will lead to manifestation of disease.
“The classical vulnerabilitystress model of mental disorders, arguably one of the most influential models of disorder development, as well as conceptually similar approaches such as the”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Bayer, Falkai, & Maier, 1999
These findings support a two-hit model in which early life stress confers vulnerability to psychiatric symptoms, but symptom onset occurs only after a subsequent stressor.
“These studies support a “two hit” model in which ELS, such as maternal separation, confers vulnerability to symptoms of psychiatric illness, but with symptom onset only occurring after exposure to a subsequent stressor (Bayer et al., 1999; Maynard et al., 2001).”
From The effects of early life stress on reward processing (2018) · cites this paper as Bayer et al., 1999

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“Schizophrenia is a complex group of disorders in which genetic vulnerability may lead to greater sensitivity to adverse environmental conditions (Bayer et al., 1999; van Os et al., 2008, 2010; Tost and Meyer-Lindenberg, 2012).”
Background
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Authors: Bayer, T. A., Falkai, P., & Maier, W.
Affiliations: University of Bonn (DE)
Corresponding author: Maier, Wolfgang
ORCID: Bayer, Thomas A
Falkai, Peter
Venue: Journal of Psychiatric Research
Publisher: Elsevier BV
Published: 1999-11
Volume: 33
Issue: 6
Pages: 543-548
ISSN: 0022-3956 (ISSN-L)
DOI: 10.1016/s0022-3956(99)00039-4
OpenAlex: W1998639400
Cited by: 346
References: 93
Citations by year: 2026: 9 · 2025: 10 · 2024: 16 · 2023: 27 · 2022: 15 · 2021: 26 · 2020: 12 · 2019: 16 · 2018: 18 · 2017: 22 · 2016: 21 · 2015: 24 · 2014: 22 · 2013: 32 · 2012: 16
FWCI: 1.91
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Psychiatric Research (publishedVersion)
PubMed (publishedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Keywords: schizophrenia, two-hit hypothesis, genetic susceptibility, brain development, synaptic pruning, ventriculomegaly, brain atrophy, gyrification index, astrocyte activation, neurodegeneration
MeSH terms: Brain, Environment, Humans, Models, Genetic, Nerve Net, Schizophrenia, Mutagenesis, Genetic Predisposition to Disease

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Genetic and non-genetic vulnerability factors in schizophrenia: the basis of the “Two hit hypothesis.”

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