Genetic Variants Associated With Resilience in Human and Animal Studies

Cahill, Stephanie; Chandola, Tarani; Hager, Reinmar

doi:10.3389/fpsyt.2022.840120

Cited by 13 publications

(6 citation statements)

References 321 publications

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“…Genetic and epigenetic factors are major contributors to vulnerability or resilience to stress ( Ising and Holsboer, 2006 ; Cahill et al, 2022 ). For example, recent studies identified a major role for the glial-derived neurotrophic factor (GDNF) in response to chronic unpredictable stress (CUS): Increased GDNF expression in nucleus accumbens and hippocampus promotes resilience and recovery from CUS ( Uchida et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

NrCAM-deficient mice exposed to chronic stress exhibit disrupted latent inhibition, a hallmark of schizophrenia

Buhusi,

Brown,

Buhusi

2024

Front. Behav. Neurosci.

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The neuronal cell adhesion molecule (NrCAM) is widely expressed and has important physiological functions in the nervous system across the lifespan, from axonal growth and guidance to spine and synaptic pruning, to organization of proteins at the nodes of Ranvier. NrCAM lies at the core of a functional protein network where multiple targets (including NrCAM itself) have been associated with schizophrenia. Here we investigated the effects of chronic unpredictable stress on latent inhibition, a measure of selective attention and learning which shows alterations in schizophrenia, in NrCAM knockout (KO) mice and their wild-type littermate controls (WT). Under baseline experimental conditions both NrCAM KO and WT mice expressed robust latent inhibition (p = 0.001). However, following chronic unpredictable stress, WT mice (p = 0.002), but not NrCAM KO mice (F < 1), expressed latent inhibition. Analyses of neuronal activation (c-Fos positive counts) in key brain regions relevant to latent inhibition indicated four types of effects: a single hit by genotype in IL cortex (p = 0.0001), a single hit by stress in Acb-shell (p = 0.031), a dual hit stress x genotype in mOFC (p = 0.008), vOFC (p = 0.020), and Acb-core (p = 0.032), and no effect in PrL cortex (p > 0.141). These results indicating a pattern of differential effects of genotype and stress support a complex stress × genotype interaction model and a role for NrCAM in stress-induced pathological behaviors relevant to schizophrenia and other psychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

NrCAM-deficient mice exposed to chronic stress exhibit disrupted latent inhibition, a hallmark of schizophrenia

Buhusi,

Brown,

Buhusi

2024

Front. Behav. Neurosci.

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“…Additionally, knowledge of potential mediators of the relationship between CM and resilience, e.g. (epi)genetic factors (Cahill et al, 2022 ; Choi et al, 2019 ; Cicchetti & Rogosch, 2012 ; Gallardo-Pujol et al, 2013 ; Goldberg et al, 2013 ; Miu et al, 2017 ; Ramo-Fernández et al, 2019 ), brain structure (Roeckner et al, 2021 ) and functioning (McCrory et al, 2017 ; Ohashi et al, 2017 ; Teicher et al, 2020 ; Teicher & Samson, 2016 ), past or current mental disorder or medical condition (Ashy et al, 2020 ; Perini et al, 2023 ), personality traits (Mrazek & Mrazek, 1987 ), (insecure) attachment styles (Citak & Erten, 2021 ; Stein, 2006 ), physical activity or exercise (Arida & Teixeira-Machado, 2020 ), perceived loneliness, social network size and services, and coping strategies (Reinhard et al, 2022 ; Su et al, 2022 ; Ungar, 2013 ) could facilitate an understanding of the mechanisms underlying this association. This knowledge is important for developing risk stratification models of adverse psychosocial health outcomes and targeted effective prevention and intervention strategies for individuals with histories of CM exposure.…”

Section: Introductionmentioning

confidence: 99%

Child maltreatment and resilience in adulthood: a protocol for a systematic review and meta-analysis

Fares-Otero,

Spies

et al. 2023

European Journal of Psychotraumatology

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Background: Although child maltreatment (CM) has been linked to health problems and poor psychosocial functioning, not all individuals exposed to CM develop or experience negative consequences later in life. This suggests that some individuals show resilience after being exposed to CM. However, conclusions have been limited by inconsistent findings across different CM subtypes and resilience domains. Objective: To develop a protocol for conducting a systematic review and meta-analysis to quantify associations between CM (overall and its subtypes) and resilience (global and its multiple domains) in adulthood, and to examine moderators and mediators of these associations. Method: PubMed, PsycINFO, Embase, Scopus, and Web of Science will be searched to identify relevant studies on the association between CM (exposure) and resilience (outcome) in adults (≥ 18 years). Data will be screened and extracted by at least two independent reviewers. The methodological quality of the included studies will be independently assessed with a modified version of the Newcastle–Ottawa Scale (NOS). If deemed viable, a meta-analysis will be conducted using a random effects model. Heterogeneity of evidence will be estimated with the I 2 statistic, and publication bias will be assessed. The effects of potential moderators (e.g. timing and severity of CM, age, sex, family cohesion, socio-economic status, country/region) will be analysed using meta-regression and subgroup analyses, and meta-analytical structural equation modelling will be employed to synthesise indirect mediation effects. Candidate moderators and mediators (e.g. genetic factors, brain functioning, attachment style, personality traits, physical activity, and social support) will be also examined qualitatively. Conclusions: This protocol will facilitate a systematic review and meta-analysis that has the potential to enhance our knowledge about the association between CM exposure in early life and resilience in adulthood. Understanding associations and underlying mechanisms between CM and resilience is potentially important in informing prevention and interventions to sustain health and improve outcomes among adults with a history of CM. PROSPERO registration: CRD42023394120.

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“…APOE (apolipoprotein, apoE) encodes a major apoprotein of the chylomicron family. It has been suggested that APOE, along with FKBP5, OXTR, and CRHR1, is among the main genes associated with resilience across divergent resilience definitions [62]. Stress induces apoE synthesis as part of repair processes in the central nervous system [63].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis

Mikhailova,

Ivanoshchuk,

Orlov

et al. 2023

Genes

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Background: A socioeconomic crisis in Russia lasted from 1991 to 1998 and was accompanied by a sharp drop in the birth rate. The main factor that influenced the refusal to have children during this period is thought to be prolonged social stress. Methods: comparing frequencies of common gene variants associated with stress-induced diseases among generations born before, after, and during this crisis may show which genes may be preferred under the pressure of natural selection during periods of increased social stress in urban populations. Results: In the “crisis” group, a statistically significant difference from the other two groups was found in rs6557168 frequency (p = 0.001); rs4522666 was not in the Hardy–Weinberg equilibrium in this group, although its frequency did not show a significant difference from the other groups (p = 0.118). Frequencies of VNTRs in SLC6A3 and MAOA as well as common variants rs17689918 in CRHR1, rs1360780 in FKBP5, rs53576 in OXTR, rs12720071 and rs806377 in CNR1, rs4311 in ACE, rs1800497 in ANKK1, and rs7412 and rs429358 in APOE did not differ among the groups. Conclusions: a generation born during a period of prolonged destructive events may differ from the rest of the gene pool of the population in some variants associated with personality traits or stress-related disorders.

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Genetic Variants Associated With Resilience in Human and Animal Studies

Cited by 13 publications

References 321 publications

NrCAM-deficient mice exposed to chronic stress exhibit disrupted latent inhibition, a hallmark of schizophrenia

NrCAM-deficient mice exposed to chronic stress exhibit disrupted latent inhibition, a hallmark of schizophrenia

Child maltreatment and resilience in adulthood: a protocol for a systematic review and meta-analysis

Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis

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