Human Studies

Although placebo effect sizes in clinical trials of chronic pain treatments have been increasing, it remains unknown if characteristics of individuals' thoughts or prior experiences can reliably infer placebo pill responses. Research using language to investigate emotional and cognitive processes has recently gained momentum. Here, we quantified placebo response in chronic low back pain using over 300 semantic and psycholinguistic features derived from patients' language. This speech content was collected in an exit interview as part of a clinical trial investigating placebo analgesia (62 patients, 42 treated; 20 not treated). Utilizing a nested leave-one-out cross-validated approach, we distinguished placebo responders from non-responders with 79% accuracy using language features alone; a subset of these features – semantic distances to identity and stigma and the number of achievement-related words – also explained 46% of the variance in placebo analgesia. Importantly, these language features were not due to generic treatment effects and were associated with patients' specific baseline psychological traits previously shown to be predictive of placebo including awareness and personality characteristics, explaining an additional 31% of the variance in placebo analgesia beyond that of personality. Initial interpretation of the features suggests that placebo responders differed in how they talked about negative emotions and the extent that they expressed awareness to various aspects of their experiences; differences were also seen in time spent talking about leisure activities. These results indicate that patients' language is sufficient to identify placebo response and implies that specific speech features may be predictive of responders prior to treatment.

Pain and depression are episodic conditions that might take a chronic course. They are clearly related, but information on how they influence each other in the process of chronification is limited. Pain catastrophizing is hypothesized to play a role in the development of depression and chronic pain, but few longitudinal studies have investigated their association over a longer-term. In this study, a random cohort from the general population (n = 4764) answered questions about pain, catastrophizing, and depression at five assessments in yearly intervals. Linear mixed models showed that within persons, increases in pain intensity and catastrophizing were independently associated with increases in depressive symptoms (mean change = -1.12, 95% CI [-1.32, -0.91]) and -1.29, 95% CI [-1.52, -1.05], respectively). In prospective analyses restricted to individuals without depression above cut-off at baseline, chronic pain increased the risk of endorsing depression over the following four years (OR =2.01, 95% CI [1.71, 2.37]). Seven percent showed a chronic course of depression, as indicated by scores above cut-off on at least three of five assessments. Number of years lived with chronic pain was associated with a chronic course of depression, with odds ratios increasing from 1.55 (95% CI [0.87, 2.91]) to 14.19 (95% CI [8.99, 22.41]) when reporting chronic pain on two versus five assessments compared to none. The results suggest that when pain intensity or catastrophizing change, depressive symptoms change in the same direction. When pain and catastrophizing become chronic, they appear to be mutually reinforcing determinants for chronic depression.

Biased interpretations of ambiguous bodily threat situations characterise youth with chronic pain, and have been associated with functional disability for this population. Despite predictions by the fear-avoidance model of chronic pain, that fear and avoidance of pain explain the association between threat perceptions and disability, this has not yet been explored in youth with chronic pain. The current study aimed to address this gap by investigating these proposed relationships, in addition to the association between bodily threat interpretations and daily aspects of disability (as well as social, and emotional impairments).