Regions activated by a contrast of Attend CS+ versus Regulate CS+ and vice versa (p<0.001).

<p>Regions activated by a contrast of Attend CS+ versus Regulate CS+ and vice versa (p<0.001).</p

BOLD signals in the right dACC.

<p>(A) Activation of the right dACC reflected by the contrast between Regulate CS+ and Attend CS+ trials (cognitive reappraisal effects). (B) Mean beta weights from the right dACC showed an interaction of type of instruction and type of CS. (C) Craving significantly correlated with the differential dACC response to the Attend CS+ trials compared with the Regulate CS+ trials (r = −0.92, p<0.01; Fig. 2C). Craving scores during the cognitive strategies were calculated by subtracting the craving during Regulate CS+ trials from craving during Attend CS+ trials for each participant.</p

Table_1_Causal association between the peripheral immunity and the risk and disease severity of multiple sclerosis.xlsx

BackgroundGrowing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear.MethodsMendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed.ResultsMR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4+ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25++CD4+ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25++CD4+ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25++CD4+ T cell in CD4+ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25++CD8+ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4+ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04).ConclusionsThis study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.</p