Evidence for an apr that accompanies major depression was first reported by Maes et al. (1992a, b). The apr is reflected, too, in lowered levels of total serum protein (TSP) and changes in the major electrophoretically separated serum protein fractions. Several investigators (e.g. Schwartz et al., 1990; Joyce et al., 1992; Song et al., 1994a; Maes et al., 1991, 1995b) reported lowered levels of serum albumin (Alb) in major depressed patients suffering major depression compared to normal controls. Interestingly, in the olfactory bulbectomized (OB) rat model of depression, Song and Leonard (1994b) found lower levels of Alb. The different apps migrate electrophoretically between Alb and gamma-globulin fractions. Apps such as AGP, ACT, CRP migrate in the alpha-1 zone, Hp and Cp migrate in the alpha-2 zone, fibrinogen and C3 migrate in the p zone, and immunoglobulines in the gamma-zone (Ritzmann and Daniels, 1976). This may explain why during apr there are alterations in TSP and in electrophoretically separated serum protein fractions (Putnam, 1984a, b).
There are only a few studies examining serum protein fractions in major depression. Song and Leonard (1993) reported increased levels of alpha-1 and alpha-2 globulin fractions in depression and Maes et al. (1995b) found increased levels of alpha-2 globulin and gamma-globulin. Recently, Van Hunsel et al. (1996) reported in 37 major Hpnrecsprl natients of whom 79 nresented TRD lowered levels of TSP alb. and B—as well as gamma-globulin. The percentages of alpha-1 and alpha-2 globulin fractions were significantly higher in major depressed and TRD patients than in normal controls, and alpha-2 globulins were lower in TRD patients than in responders.
We have recently reported (Sluzewska et al., 1997b) decreased levels of TSP and Alb as well as elevated levels of alpha-1 and alpha-2, and a higher percentage of alpha-1, alpha-2, and gamma-globulin in 49 major depressed patients in comparison with normal controls. In the same sudy, 25 TRD patients compared with responders were found to have higher percentages of alpha-1 and gamma-globulin. In the TRD patients, there were positive correlations between AGP, ACT, and alpha-1 globulin. The basal morning Cortisol values were significantly and positively correlated with AGP, ACT, alpha-1, alpha-2, [3, and gamma globulin, and negatively correlated with albumin (Sluzewska et al., 1997b). In these patients, a positive correlation was also found between serum levels of IL-6 and alpha-1 globulin and a negative correlation was demonstrated between IL-6 and albumin.
These findings of increased serum alpha-1, alpha-2, and gamma-globulin percentages, taken together with the indications of lowered TSP and Alb, may point toward an elevated production of apps migrating in the alpha-1 and alpha-2 and immunoglobulins (majority of IgG, IgM, IgA) of the gamma electrophoretical zone, associated with elevated protein catabolism.
Taken together, these results support the hypothesis that major depression and, in particular, treatment-resistent-depression may be accompanied by alterations of the acute phase response.
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