2009, 2010). Of these, matched subsets of 39 and 46 also completed functional magnetic resonance imaging (fMRI) (Williams et al. 2009, 2010). Assessments: Heart rate and fMRI were recorded during a facial emotion viewing task, under both conscious and nonconscious conditions. DNA was extracted from cheek swab samples and Bak apoptosis genotyped for the polymorphism of the serotonin transporter gene (5-HTT-LPR) and COMT Val108/158Met genotypes (for details of Methods, Williams et al. 2009, 2010). Validation outcomes: Greater fear reactivity Inhibitors,research,lifescience,medical indexed by both heart rate and

activation of brainstem, amygdala, and medial prefrontal cortex circuitry was associated with greater negativity relative to positivity bias. This association was pronounced in individuals with the “risk” alleles, 5 HTT-LPR Short and COMT Met. The findings indicate that a higher negativity bias is underpinned by genetic and fear circuitry susceptibility for emotional disorder. Ecological validation with real-world functional capacities The association between the Inhibitors,research,lifescience,medical full BRISC and proxy measures of real-world functional outcomes was established in the same sample of 55 participants used to assess construct validation against the ERQ and IC. These proxy measures included the following: Quality Inhibitors,research,lifescience,medical of Life assessed by

the World Health Organizations Qualify of Life scale, brief version (WHOQOL-BREF) scale (World Health Organization Group 1998) Satisfaction with Life Scale (SWLS; Diener et al. 1985) Work productivity, in terms of both absenteeism (hours absent from work) and presenteeism (performance level), assessed Inhibitors,research,lifescience,medical using the Health and Work Performance Questionnaire (HPQ; Kessler et al. 2003) Validation outcomes: Correlation analyses between the BRISC scales and the WHOQOL-BREF, SWLS, and HPQ, at a corrected P-value of 0.01, demonstrated the following associations: Negative correlations between lower negativity–positivity bias and higher WHOQOL-BREF psychological (r = −0.50, P < 0.0001) and social relationships (P = −0.39, P = 0.003) components of quality of life, and the presenteeism component of the productivity on the HPQ (r = −0.39, P = 0.01) Inhibitors,research,lifescience,medical Positive correlations between higher emotional

resilience and higher scores on the WHOQOL-BREF psychological component (r = 0.52, P < 0.0001) and satisfaction with life on the SWLS (r = 0.34, P = 0.01) Positive correlations between higher social skills and higher scores on the WHOQOL-BREF components to of physical health (r = 0.45, P = 0.001) and environment (r = 0.56, P < 0.0001), satisfaction with life (r = 0.42, P = 0.001) and presenteeism on the HPQ (r = 0.37, P = 0.008) Study research sites Participants were recruited from 12 medical research or clinical research sites. These sites agreed to collaborate as partners with Brain Resource to evaluate brain health in patients using a standardized set of assessments and contribute the data to a centralized library (the Brain Resource International Database).