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

• Published in: British journal of psychiatry 2020-11, Vol.217 (5), p.645-650
• Main Authors: Schiele, Miriam A., Herzog, Katharina, Kollert, Leonie, Schartner, Christoph, Leehr, Elisabeth J., Böhnlein, Joscha, Repple, Jonathan, Rosenkranz, Karoline, Lonsdorf, Tina B., Dannlowski, Udo, Zwanzger, Peter, Reif, Andreas, Pauli, Paul, Deckert, Jürgen, Domschke, Katharina
• Format: Article
• Language: English
• Subjects: Ability; Adaptation, Psychological; Adult; Adversity; Anxiety; Anxiety - genetics; Anxiety - psychology; Anxiety disorders; Anxiety Disorders - genetics; Anxiety Disorders - psychology; Child abuse & neglect; Childhood; Children; Coping; Critical incidents; Discovery; Female; Gene-Environment Interaction; Genotype; Genotype & phenotype; Genotypes; Homozygotes; Humans; Male; Mental disorders; Moderators; Neuropeptides; Panic attacks; Psychiatry; Receptors, G-Protein-Coupled - genetics; Regression analysis; Replication; Resilience; Self Efficacy; Stress; Therapeutic applications; Trait anxiety; Trauma; Vulnerability
• ISSN: 0007-1250; 1472-1465
• DOI: 10.1192/bjp.2020.73

The general understanding of the 'vulnerability-stress model' of mental disorders neglects the modifying impact of resilience-increasing factors such as coping ability. 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. 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. 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. 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.