Negative symptoms and their association with depressive symptoms in the long-term course of schizophrenia.

Depressive symptoms abound in schizophrenia and even in subclinical states of the disorder. We studied the frequency of these symptoms and their relationship to negative symptoms from the first psychotic episode on over a long-term course of 134 months on data for 107 patients in our ABC Schizophrenia Study. Prevalence rates of 90 % for presenting at least one negative symptom and of 60 % for presenting at least one depressive symptom in the first psychotic episode illustrate the frequency of these syndromes. After the remission of psychosis the rates fell to 50 % (negative symptoms) and 40 % (depressive symptoms) over a period of 5 years, remaining stable thereafter. After we broke the negative syndrome down into (SANS) subsyndromes, a positive association emerged between anhedonia and depressive symptoms and remained stable over the entire period studied. In contrast, the association between abulia and depression grew increasingly pronounced over the illness course. However, a more detailed look revealed this to be the case in female patients only, whereas male patients showed no such association of these symptom dimensions. We have no explanation at hand for this sex difference yet.

Pregnancy: tolerance and suppression of immune responses.

Presence of foreign tissue in a host's body would immediately lead to a strong immune response directed to destroy the alloantigens present in fetus and placenta. However, during pregnancy, the semiallogeneic fetus is allowed to grow within the maternal uterus due to multiple mechanisms of immune tolerance, which are discussed in this chapter.

Regulatory T cells and their role in pregnancy.

Regulatory T cells emerge in the last years as key players in allowing fetal survival within the maternal uterus. They were shown to be a unique subpopulation of T cells expanding during human and murine pregnancy. The importance of Treg for a normal pregnancy situation was proven by studies showing that their absence impairs murine pregnancy while the adoptive transfer of Treg prevents fetal rejection. In humans, pregnancy pathologies are associated with lower Treg frequencies while therapies that improve pregnancy outcome are able to boost their number. Functional studies have shown that Treg can regulate immune cell responses directly at the fetal-maternal interface either by interacting with other cells or by inducing the expression of immune regulatory molecules. This article revises relevant literature on regulatory T cells in human and murine pregnancy.

The persistence of paternal antigens in the maternal body is involved in regulatory T-cell expansion and fetal-maternal tolerance in murine pregnancy.

PROBLEM: Mammalian pregnancy is a state of immunological tolerance and CD4(+) CD25(+) regulatory T cells (Treg) contribute to its maintenance. Knowing that Treg act in an antigen-specific way during pregnancy, we hypothesized that they are generated after maternal immune cells encounter paternal antigens. METHOD OF STUDY: We mated wild type females with transgenic green fluorescent protein (GFP) males in an allogenic setting and killed them on different days of pregnancy. RESULTS: Presence of paternal and maternal MHC class II(+) cells in vaginal lavage on day 0.5 of pregnancy was confirmed. Thus, antigen presentation may take place early during pregnancy in the periphery either by the direct or indirect pathways. Foxp3(+) cells known to have regulatory activity could be detected on day 2 of pregnancy in lymph nodes and shortly after implantation at the fetal-maternal interface. CONCLUSION: Our data suggest that paternal antigens are processed early during pregnancy, which leads to the generation of Treg. The continuous release of placental antigens into the maternal circulation allows the maintenance of a Treg population which is specific for paternal antigens and mediates tolerance toward the semi-allogeneic fetus until the time point of birth.