Eyeing ambiguity: Pupillary reactivity during early automatic interpretations in major depressive disorder.

Automatic interpretation biases (AIB) are theorized to be a risk factor for depression. However, documenting AIB in depressed persons has been challenging and the source (affective vs cognitive) of AIB remains unclear. We conducted a psychophysiological investigation of AIB in a sample of 25 clinical interview assessed individuals experiencing a current major depressive episode and 28 never-depressed control individuals. Participants completed the Word Sentence Association Paradigm for Depression while their pupil size was recorded. Repeated measures ANOVAs were used to examine behavioral response data and multilevel modeling was used to examine pupillary reactivity (change from trial baseline). Compared to controls, the depressed group was both more likely to endorse negative AIB (p = .001, d = 1.01) and less likely to endorse benign AIB (p = .011, d = 0.72). Further, the depressed group exhibited significantly increased pupil size while processing negative words when they endorsed a negative interpretation compared with controls (ps = .010-.037, ds = 0.69-0.87), but did not differ during other AIB trial types. Within group comparisons revealed greater differentiation between interpretations in the healthy control group in both reaction time and pupillary reactivity AIB measures. This depression-related pupillary reactivity pattern fits with an emotional salience-based explanation better than a cognitive effort-based hypothesis of negative AIB, while pupillary reactivity pattern within the control group is consistent with a benign bias. People with depression lack benign AIB and may be more emotionally engaged during negative AIB than healthy controls.