'Negativity bias' in risk for depression and anxiety: brain-body fear circuitry correlates, 5-HTT-LPR and early life stress.

The INTEGRATE Model draws on the framework of 'integrative neuroscience' to bring together brain-body and behavioral concepts of emotion, thinking and feeling and their regulation. The key organizing principle is the drive to 'minimize danger and maximize reward' that determines what is significant to us at each point in time. Traits of 'negativity bias' reflect the tendency to perceive danger rather than reward related information, and this bias influences emotion, thinking and feeling processes. Here, we examined a self-report measure of Negativity Bias in relation to its impact on brain and body correlates of emotion processing. The contributions of the serotonin transporter (5-HTT-LPR) allelic variants and early life stress to both negativity bias and these correlates were also examined. Data were accessed in collaboration with the Brain Resource International Database (BRID) which provides standardized data across these domains of measurement. From an initial sample of 303 nonclinical subjects from the BRID, subjects scoring one standard deviation below (n=55) and above (n=47) the mean on the measure of negativity bias were identified as 'Negativity Bias' and 'Positivity Bias' groups for analysis, respectively. These subjects had been genotyped for 5-HTT-LPR Short allele versus LL homozygote status, and completed the early life stress scale, and recording of startle responses and heart rate for conscious and nonconscious fear conditions. A matched subset (n=39) of BRID subjects completed functional MRI with the same facial emotion tasks. The Negativity Bias (compared to Positivity Bias) group was distinguished by both arousal and brain function correlates: higher startle amplitude, higher heart rate for conscious and nonconscious fear conditions, and heightened activation in neural circuitry for both fear conditions. Regions of heightened activation included brainstem and bilateral amygdala, anterior cingulate and ventral and dorsal medial prefrontal cortex (mPFC) for conscious fear, and brainstem and right-sided amygdala, anterior cingulate and ventral, mPFC for nonconscious fear. The 5-HTT-LPR Short allele (versus LL) conferred a similar pattern of arousal and neural activation. For those with the 5-HTT-LPR Short allele, the addition of early life stress contributed to enhanced negativity bias, and to further effects on heart rate and neural activation for nonconscious fear in particular. These findings suggest that traits of negativity bias impact brain-body arousal correlates of fear circuitry. Both genetic variation and life stressors contribute to the impact of negativity bias. Given that negativity bias is a feature of conditions such as depression and associated biological alterations, the findings have implications for translation into clinical decision support.