The unique face of anxious depression: Exaggerated threat but preserved positive valence reactivity

Background Even though anxious depression is among the most prevalent psychiatric conditions; its underlying neural and behavioral characteristics remain not well understood. This may be important to break down heterogeneity in depression. This study investigated the unique profile of individuals with anxious depression using affective startle modulation, a process known to independently probe appetitive/defensive systems and known to be affected by mood and anxiety disorders Methods 236 depressed participants of the Tulsa 1000 study completed multi-level assessments including an emotional reactivity task with eye-blink startle measurement. To minimize bias due to covariates, 124 participants with comorbid depression and anxiety disorders (Dep+Anx) were matched with 62 participants with depression only (Dep). Eye-blink startle magnitudes during positive/negative visual cues were analyzed. Results The Dep group showed no affective modulation of startle. However, the Dep+Anx group showed potentiation from aversive cues and attenuation from appetitive cues. The Dep+Anx group also showed increased attenuation from appetitive cues compared to the Dep group. Dimensionally, the effect of self-report anxiety on startle was moderated by self-report depression. Conclusions Compared to individuals with depression, those with anxious depression demonstrate heightened positive/negative startle modulation, with depression levels moderating the link between anxiety sensitivity and startle reflex. The differences between these groups in processing aversive/appetitive information support the conclusion that these depression subtypes should be considered separately in future clinical trials. ClinicalTrials.gov identifier: # NCT02450240 . General scientific summary This study suggests that there are striking differences between those with anxious and non-anxious depression. Specifically, these two groups differ in terms of threat reactivity measured by eye-blink startle response. This proposes that the two groups be separated in future clinical trials.