Extending the vulnerability-stress model of mental disorders: three-dimensional NPSR1 × environment × coping interaction study in anxiety

TY - JOUR

T1 - Extending the vulnerability-stress model of mental disorders: three-dimensional NPSR1 × environment × coping interaction study in anxiety

AU - Schiele, Miriam A

AU - Herzog, Katharina

AU - Kollert, Leonie

AU - Schartner, Christoph

AU - Leehr, Elisabeth J

AU - Böhnlein, Joscha

AU - Repple, Jonathan

AU - Rosenkranz, Karoline

AU - Lonsdorf, Tina B

AU - Dannlowski, Udo

AU - Zwanzger, Peter

AU - Reif, Andreas

AU - Pauli, Paul

AU - Deckert, Jürgen

AU - Domschke, Katharina

PY - 2020/11

Y1 - 2020/11

N2 - BACKGROUND: The general understanding of the 'vulnerability-stress model' of mental disorders neglects the modifying impact of resilience-increasing factors such as coping ability.AIMS: Probing a conceptual framework integrating both adverse events and coping factors in an extended 'vulnerability-stress-coping model' of mental disorders, the effects of functional neuropeptide S receptor gene (NPSR1) variation (G), early adversity (E) and coping factors (C) on anxiety were addressed in a three-dimensional G × E × C model.METHOD: In two independent samples of healthy probands (discovery: n = 1403; replication: n = 630), the interaction of NPSR1 rs324981, childhood trauma (Childhood Trauma Questionnaire, CTQ) and general self-efficacy as a measure of coping ability (General Self-Efficacy Scale, GSE) on trait anxiety (State-Trait Anxiety Inventory) was investigated via hierarchical multiple regression analyses.RESULTS: In both samples, trait anxiety differed as a function of NPSR1 genotype, CTQ and GSE score (discovery: β = 0.129, P = 3.938 × 10-8; replication: β = 0.102, P = 0.020). In A allele carriers, the relationship between childhood trauma and anxiety was moderated by general self-efficacy: higher self-efficacy and childhood trauma resulted in low anxiety scores, and lower self-efficacy and childhood trauma in higher anxiety levels. In turn, TT homozygotes displayed increased anxiety as a function of childhood adversity unaffected by general self-efficacy.CONCLUSIONS: Functional NPSR1 variation and childhood trauma are suggested as prime moderators in the vulnerability-stress model of anxiety, further modified by the protective effect of self-efficacy. This G × E × C approach - introducing coping as an additional dimension further shaping a G × E risk constellation, thus suggesting a three-dimensional 'vulnerability-stress-coping model' of mental disorders - might inform targeted preventive or therapeutic interventions strengthening coping ability to promote resilient functioning.

AB - BACKGROUND: The general understanding of the 'vulnerability-stress model' of mental disorders neglects the modifying impact of resilience-increasing factors such as coping ability.AIMS: Probing a conceptual framework integrating both adverse events and coping factors in an extended 'vulnerability-stress-coping model' of mental disorders, the effects of functional neuropeptide S receptor gene (NPSR1) variation (G), early adversity (E) and coping factors (C) on anxiety were addressed in a three-dimensional G × E × C model.METHOD: In two independent samples of healthy probands (discovery: n = 1403; replication: n = 630), the interaction of NPSR1 rs324981, childhood trauma (Childhood Trauma Questionnaire, CTQ) and general self-efficacy as a measure of coping ability (General Self-Efficacy Scale, GSE) on trait anxiety (State-Trait Anxiety Inventory) was investigated via hierarchical multiple regression analyses.RESULTS: In both samples, trait anxiety differed as a function of NPSR1 genotype, CTQ and GSE score (discovery: β = 0.129, P = 3.938 × 10-8; replication: β = 0.102, P = 0.020). In A allele carriers, the relationship between childhood trauma and anxiety was moderated by general self-efficacy: higher self-efficacy and childhood trauma resulted in low anxiety scores, and lower self-efficacy and childhood trauma in higher anxiety levels. In turn, TT homozygotes displayed increased anxiety as a function of childhood adversity unaffected by general self-efficacy.CONCLUSIONS: Functional NPSR1 variation and childhood trauma are suggested as prime moderators in the vulnerability-stress model of anxiety, further modified by the protective effect of self-efficacy. This G × E × C approach - introducing coping as an additional dimension further shaping a G × E risk constellation, thus suggesting a three-dimensional 'vulnerability-stress-coping model' of mental disorders - might inform targeted preventive or therapeutic interventions strengthening coping ability to promote resilient functioning.

U2 - 10.1192/bjp.2020.73

DO - 10.1192/bjp.2020.73

M3 - SCORING: Journal article

C2 - 32321595

VL - 217

SP - 645

EP - 650

JO - BRIT J PSYCHIAT

JF - BRIT J PSYCHIAT

SN - 0007-1250

IS - 5

ER -