Identifying biological pathways that underlie individual differences in emotional reactivity and regulation may help to clarify how such differences confer vulnerability to psychiatric disease. This dissertation examines the role of individual differences in (1) emotion regulation usage (reappraisal), (2) personality (neuroticism), and (3) genetics (5-HTTLPR), and how they impact neural substrates of emotional reactivity and regulation using a multi-method approach.

Study 1 used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine whether individual differences in reappraisal use predict neural responses when individuals are confronted with negative images. Fifty-six healthy women completed an fMRI challenge paradigm involving the perceptual processing of emotionally negative facial expressions and provided measures of typical emotion regulation use. Results showed that greater use of reappraisal in everyday life was related to decreased amygdala activity and increased prefrontal and parietal activity during the processing of negative emotional facial expressions. These findings suggest that individual differences in reappraisal use are associated with decreased activation in ventral emotion generative regions and increased activation in prefrontal control regions in response to negative stimuli. Such individual differences in emotion regulation may predict successful coping with emotional challenges as well as the onset of affective disorders.

Study 2 examined the biobehavioral impact of varying levels of anticipatory anxiety, using a shock anticipation task in which unpredictable electric shocks were threatened and delivered to the wrist at variable intervals and intensities (safe, medium, strong). This permitted investigation of a dynamic range of anticipatory anxiety responses. In two experiments, 95 and 51 healthy female participants, respectively, underwent this shock anticipation task while providing continuous ratings of anxiety experience and electrodermal responding (Experiment A) and during BOLD fMRI neuroimaging (Experiment B). Results indicated a step-wise pattern of responding in anxiety experience, electrodermal responses, and neural activity. These responses were modulated by individual differences in neuroticism, such that those high in neuroticism showed exaggerated anxiety experience across the entire task, and reduced brain activation from medium to strong trials in a subset of brain regions. These findings suggest that individual differences in neuroticism may influence sensitivity to anticipatory threat and provide new insights into the mechanism through which neuroticism may confer risk for developing anxiety disorders via dysregulated anticipatory responses.

Study 3 investigated whether differences in 5-HTTLPR genotype impacted neural responses to the threat task developed in Study 2. While many studies have shown that 5–HTTLPR genotype interacts with exposure to stress in conferring risk for psychopathology, the specific neural mechanisms through which this gene by environment interaction confers risk remain largely unknown. Relative to those carrying the L allele, SS homozygotes showed enhanced activation during threat anticipation in a network of regions including amygdala, hippocampus, anterior insula, thalamus, pulvinar, caudate, precuneus, anterior cingulate, and dorsomedial prefrontal cortex (dmPFC). SS homozygotes also displayed enhanced positive coupling between dmPFC activation and anxiety experience, whereas individuals carrying the L allele displayed enhanced negative coupling between insula activation and perceived success at regulating anxiety. Taken together, the present findings suggest that, when exposed to stress, SS homozygotes may preferentially engage neural systems which enhance fear and arousal, modulate attention toward threat, and perseverate on emotional salience of the threat. In turn, this may be a mechanism underlying risk for psychopathology conferred by the S allele upon exposure to life stressors.