In patients with major depressive disorder (MDD), positive valence (PV) and negative valence (NV) system functions seem to be reflected in select clinical symptoms that are differentially associated with other clinical features, immunologic function, and treatment outcomes, according to study results published in Depression and Anxiety.

The investigators examined clinical data obtained from 665 participants with MDD from the single-blind, randomized, placebo-controlled combining medications to enhance depression outcomes (CO-MED) study ( identifier: NCT00590863). Additionally, they assessed immunomarkers in a subset of 166 individuals who participated in an optional biomarker study.

The items included to reflect PV systems were impairments in (1) capacity for pleasure or enjoyment; (2) general interest; (3) response of mood to desired events; (4) energy level; and (5) interest in sex. In contrast, the items reflecting NV systems were (1) feeling anxious or tense; (2) panic/phobic symptoms; and (3) interpersonal sensitivity. The researchers created 2 scales representing PV and NV symptom scores by adding the individual symptom scores for each item. The researchers evaluated specific MDD symptoms and overall symptom severity, and participants completed several self-report questionnaires.

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The following immunomarkers, which have been previously associated with MDD, were evaluated: C-reactive protein, interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-α. These immunomarkers were divided into 2 groups based on their inflammatory properties: primarily pro- or anti-inflammatory.

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Results of the study demonstrated that PV symptoms were independently associated with being a woman (P <.001), older age (P =.012), and higher cognitive and physical impairment (P <.001). On the other hand, NV symptoms were independently associated with younger age (P =.013), generalized anxiety disorder (P =.001), social phobia (P =.002), and other commonly related noncriterion symptoms (P <.001).

Generally, PV symptoms were significantly more responsive to antidepressants than NV symptoms (Cohen d, 0.455; P <.0001). Furthermore, a PV symptom score was positively associated with the concentration of 3 pro-inflammatory factors and 1 anti-inflammatory factor, particularly interferon-γ and IL-6. Moreover, an NV symptom score was negatively correlated with only 1 pro-inflammatory immunomarker, IL-2.

The investigators noted that the study was limited by a low internal consistency for the NV symptom score, and the limited data on the biomarkers component of the study. They concluded that the results of this study show that PV and NV symptom scores were linked to distinct clinical and immunologic features, although the scores reported were also modestly and positively associated with each other.

Disclosures: Several study authors reported relationships with pharmaceutical companies and other entities. Please see original paper for a full list.


Medeiros GC, Rush AJ, Jha M, et al. Positive and negative valence systems in major depression have distinct clinical features, response to antidepressants, and relationships with immunomarkers [published online March 18, 2020]. Depress Anxiety.

doi: 10.1002/da.23006.