Associations between negative symptoms and thermal pain perception in bipolar I disorder

There is emerging evidence that negative symptoms are a source of functional impairment for individuals with bipolar I disorder (BD). Patients with BD may also demonstrate notable changes in the perception of pain. The objective of this preliminary study was to explore potential associations between negative symptom severity and pain perception (measured with quantitative sensory testing (QST)) in BD as well as identify neurobiological correlates of these two domains.

In patients with BD (N = 24, 30.3 ± 9.4 years of age), the Clinical Assessment Interview for Negative Symptoms (CAINS) Total and CAINS Motivation and Pleasure (MAP) subscale scores were associated with cold pain detection thresholds (CAINS Total: ρ = -0.49, p_UNC = 0.02, p_FDR = 0.09; CAINS MAP: ρ = -0.61, p_UNC = 0.003, p_FDR = 0.047; controlled for chlorpromazine (CPZ)-equivalent dose and Montgomery-Åsberg Depression Rating Scale (MADRS) scores). Parallel findings were observed for heat pain detection thresholds (CAINS Total: Spearman's ρ = 0.55, p_UNC = 0.009, p_FDR = 0.057; CAINS MAP: ρ = 0.54, p_UNC = 0.01, p_FDR = 0.057). Associations among CAINS expression scores and any QST-based measure less robust. An advanced multi-tensor model of crossing fibers was used to analyze Diffusion Tensor Imaging (DTI) data (N = 20). Here, the fractional anisotropy (FA) of the superior longitudinal fasciculus I (SLF-I), a white matter pathway integrating sensorimotor (Brodmann areas 5 and 7), parietal, and frontal cortices was associated with negative symptom severity (CAINS Total: ρ = -0.55, p_UNC = 0.019, p_FDR = 0.09; CAINS MAP: ρ = -0.56, p_UNC = 0.016; p_FDR = 0.09). A slightly more moderate trend between the FA of SLF-I and heat pain detection thresholds (ρ = -0.48, p_UNC = 0.044; p_FDR = 0.26) and heat pain tolerances (ρ = -0.53, p_UNC = 0.022; p_FDR = 0.26) was observed.

This preliminary study points to the relationship among negative symptom severity and the perception of pain in adults with BD. These findings suggest that thermal pain hypoalgesia in patients with BD may serve as a behavioral marker of negative symptoms, particularly in the MAP domain, potentially reflecting disruptions in sensory-affective integration. Further research with larger samples is warranted to clarify underlying neurobehavioral mechanisms.