Previous reports have shown that during chronic inflammation, the tryptophan (TRP)-kynurenine (KYN) pathway plays a pivotal role in the onset of depression. The aim of this study was to investigate the characteristics of the serum TRP-KYN pathway metabolite profile in high-risk subjects of major depressive disorder (HRMDD) defined by depression scores. The concentrations of TRP-KYN pathway metabolites {TRP, KYN, 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), kynurenic acid (KYNA) and anthranilic acid (AA)} were assessed in serum from HRMDD, chronic pain disorder patients and healthy controls. In serum from HRMDD, elevated levels of AA and decreased levels of TRP were observed, but the levels of other metabolites were not changed. Furthermore, the change in the AA 2nd / AA 1st ratio in subjects who progressed from a healthy state to a depressive state was correlated with an increase in the CES-D score. The level of IL-1 receptor antagonist (IL-1RA) was negatively correlated with that of AA. Interestingly, we confirmed AA as a possible biomarker for depression-related symptoms, since the metabolite profiles in the chronic pain disorder group and chronic unpredictable mild stress model mice were similar to those in the HRMDD. These results suggest that AA may be an effective marker for HRMDD. More than 300 million people suffered from major depressive disorder (MDD) in 2017, and the number is increasing year by year 1. Several theories of MDD onset have been proposed 2. The monoamine hypothesis, the chronic inflammation hypothesis, and the abnormalities in the hypothalamus-pituitary-adrenal (HPA) system hypothesis are the predominant hypotheses regarding the pathogenesis of MDD 3. Among these hypotheses, the chronic inflammation hypothesis is closely associated with the kynurenine (KYN) pathway 4. The KYN pathway is one of several tryptophan (TRP) metabolism pathways, and it is the main pathway involved in TRP metabolism 5,6. Inflammatory cytokines such as IFN-γ induce the expression of indoleamine 2,3-dioxygenase (IDO1), which is a

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We study various effects on both the analyzing powers and the cross sections for the (p,2p) reactions. Numerical calculations with the nonrelativistic distorted wave impulse approximation are carried out for the cross sections and the analyzing powers for the 40Ca(p, 2p)39K reaction at 101.3, 200 and 300 MeV using the effective nucleon· nucleon interaction. We take into account both the effect of the spin·orbit interaction for the distorted waves and the off-shell effect of the proton-proton scattering. It is found that the data for 101.3 and 200 MeV are in good agreement with our calcula-'tions. However, in the case of 300 MeV, significant discrepancies between the experimental results and the calculated ones have been shown. We study the sensitivity to the choices of distortion parameters of the optical potentials. Also, for the first time we examine nonlocality effects for both the distorted wave functions and the bound state ones. Finally we study the effects of relativistic corrections in the distorted wave functions and factorization corrections. The incident energy dependence of the various corrections to the cross section and the analyzing power was found not to be so large. Although the inclusion of the various corrections has some effects upon the NR-DWIA calculations, it does not significantly affect the quality of the agreement with the data of 300 MeV. § 1. IntroductionThe (p,2p) reaction 1 )-3) has played a fundamental role in studying our present picture of nuclear structure. It has provided quite direct information about singleparticle properties such as single nucleon separation energies, wave functions, and spectroscopic factors. In recent years, interest has been renewed in the study of the (p, 2p) reactions both by the start of experimental studies 4)-6) using a polarized proton beam and by great progress in the theoretical studies 7HO ) of the effective N-N interaction. Theoretical analyses ll ),12) of the (p, 2p) reactions have usually been made using the nonrelativistic distorted wave impulse approximation (NR-DWIA), including both the effect of the spin-orbit interaction for the distorted waves and the off-shell effect in the proton-proton t-matrix elements. Recently, the NR-DWIA calculations 12H5 ) have been used successfully in the analysis ofthe cross sections and the analyzing powers of the (p, 2p) reactions on 1p and 2s-1d shell nuclei. Data for the 40Ca CP, 2p) 39 K and 160(p, 2P)15N reactions at 76.1, 101.3 and 200 MeV, and for the 12C( p, 2p)llB reaction at 84.0 MeV are in good agreement with the NR-DWIA calculations. It has been shown that the calculated individual contributions 15 ) of the central, spin-orbit and tensor parts in the effective N -N interaction to the cross sections and the analyzing powers strongly depend on the incident proton energies. Fairly consistent values of the spectroscopic factors have been obtained. The factorization approximation 13 ),14) is found to be valid even at energies as low as about 80 MeV. However, in the cases of the 40Ca( p, 2p ) 39 K rea...

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The cross sections and the analyzing powers for the Ca(p, 2p) reactions at E~= 76. 1, 101. 3, and 200 MeV are calculated in the distorted-wave impulse approximation using the Love-Franey effective nucleon-nucleon interaction. It is shown that the calculated individual contributions of the central, spin-orbit, and tensor parts in the Love-Franey interaction to the cross sections and the analyzing powers strongly depend on the incident proton energies. The spectroscopic factors extracted are consistent with the other reaction studies.In our previous publication, ' we presented the calculated results of analyzing powers and cross sections for the ' O(p, 2p) and Ca(p, 2p) reactions at E =200 MeV in the distorted-wave impulse approximation (DWIA). We have shown that the realistic treatment for the calculation of the nucleon-nucleon (N N) off'-sh-ell t matrix is quite important for both the analyzing power and the cross section. It has been found that although there are substantial contributions from the spin-orbit and the ten-I sor paj. ts in the effective N-X interaction to the cross section, the contributions from the central part are quite weak. Therefore, it seems to be very interesting to further study whether the effect of the central part on the cross section is always small at other incident energies.The transition matrix element' for the A (a, ab)C reaction on the factorization assumption in the DWIA is given bỹThe detailed derivation of the expression and an explanation of the notation have been given in our previous paper. ' The distorted-wave functions y' -"' (k tt, r &) are cali t culated by making use of the optical potentials including spin-orbit distortion. The factor (~r, b~), in Eq. (1) is the antisymmetrized a-b t matrix element with the initial momentum k, "b and the final one k, 'b', where the a -b transition operator is~, b. The bound-state relative wave function for a nucleon in the target nucleus 3 is @t (r). Thẽ , b operator is expressed in the form of a two-nucleon potential which consists of the central, spin-orbit, and tensor parts, r,b=g(ro +H L S+r2 S,b)P P (2) S, T where the relative orbital angular momentum and the total spin operators in the two-nucleon system are denoted by L and S, respectively. Here, S, b and P (P ) are the usual tensor operator and the projection operator on the spin S (isospin T) states, respectively. The radial parts of , b are taken to be sums of Yukawa forms with different ranges. The interaction strengths are given in Ref. 2. In the present paper, the analyzing powers and the cross sections for the Id&&2 state for the Ca(p, 2p) reactions 4 at E =76. 1 MeV (at angle pair 8, =30', gb =49'), 101. 3 MeV (0, =52. 2, 0b =29'), 200 MeV (0, =30', Ob =54') are calculated in the DWIA using the Love-Franey (LF) interaction of Eq.(2). We take account of both the effect of the spin-orbit interaction for the distorted waves and the off-shell behavior of the effective X-N interaction. The parameters of the proton optical potentials for Ca are constructed by the interpo...