Cytokine imbalance in the pathophysiology of major depressive disorder.

OBJECTIVE: A substantial body of evidence indicates that dysregulation of the immune system is associated with Major Depressive Disorder (MDD). Because most cytokines have pleiotropic effects, we measured various subsets of cytokines to examine the association between immune response and MDD. METHODS: Forty-eight hospitalized MDD patients and 63 normal controls were recruited. We measured in vitro monocytic (IL-6 and tumor necrosis factor (TNF)-alpha), Th1 (interferon (IFN)-gamma and interleukin (IL)-2), Th2 (IL-4), and Treg (transforming growth factor (TGF)-beta1) cytokine production as well as IL-2/IL-4 and IFN-gamma/IL-4 ratios for both groups. Depressive symptoms were assessed by Hamilton Depression Rating Scale. Patients were evaluated before and after 6 weeks of antidepressant treatment. RESULTS: At admission, IL-6, TNF-alpha, TGF-beta1 production, and IFN-gamma/IL-4 ratio were significantly higher, whereas IFN-gamma, IL-2, and IL-4 were significantly lower in MDD patients. After treatment, IL-6 and TGF-beta1 production were significantly lower than before treatment. CONCLUSION: We suggest that activation of monocytic proinflammatory cytokines, and inhibition of both Th1 and Th2 cytokines may be associated with immunological dysregulation in MDD. TGF-beta1 may be associated with the regulation of monocytic cytokines as well as Th1 and Th2 cytokines in MDD.

Monocytic, Th1 and th2 cytokine alterations in the pathophysiology of schizophrenia.

A growing body of evidence suggests that changes in the serum levels and cellular production of various cytokines are associated with the immunological abnormalities of schizophrenia. Several studies have examined alterations in T helper type 1 (Th1) and T helper type 2 (Th2) cytokines in schizophrenia. We explored monocytic, Th1 and Th2 cytokines in 43 schizophrenia patients and 50 normal controls. The mitogen-induced production of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL-4, gamma-interferon (IFN-gamma) and IL-2 was measured with enzyme-linked immunosorbent assays before and after antipsychotic treatment. IL-6 and TNF-alpha production by schizophrenic patients was significantly higher than by normal controls, while IL-2, IL-4 and IFN-gamma production was significantly lower in schizophrenic patients. After 6 weeks of antipsychotic treatment, IL-6 and TNF-alpha production was significantly decreased, while IL-4, IFN-gamma and IL-2 productions were not significantly changed. Our results suggest that increased monocytic cytokines and decreased Th1 and Th2 cytokines may be associated with the immunopathogenesis of acute psychotic schizophrenia, and that antipsychotics may play an important role in immune response by decreasing elevated monocytic cytokines.

Evidence for Association between the Brain-Derived Neurotrophic Factor Gene and Panic Disorder: A Novel Haplotype Analysis.

OBJECTIVE: Panic disorder (PD) is a common psychiatric disorder with a complex etiology, and several studies have suggested that it has a genetic component. Brain-derived neurotrophic factor (BDNF) is the most abundant of the neurotrophins in the brain and is recognized for its important role in the survival, differentiation and growth of neurons. Several lines of research have suggested possible associations between the BDNF gene and PD. In this study, we investigated the BDNF 196G/A (rs6265), 11757G/C (rs16917204), and 270C/T (rs56164415) single nucleotide polymorphisms (SNPs) in order to determine an association with PD. We also identified the genetic sequence associations with PD via haplotype analysis. METHODS: Participants in this study included 136 PD patients and 263 healthy controls. Male and female subjects were analyzed separately. The genotype and allele frequencies of the PD patients and controls were analyzed using χ(2) statistics. Frequencies and haplotype reconstructions were calculated using the SNP analyzer 2.0. RESULTS: We found no significant statistical differences in the genotype distributions or allele frequencies of the three tested polymorphisms between the PD and control groups. In addition, no differences were found between PD patients and the controls in either male or female subgroups. However, we found that, the frequency of the G-C haplotype for 196G/A and 11757G/C was significantly higher in PD patients than in the controls. CONCLUSION: Our result suggest that patients with the G-C haplotype for 196G/A and 11757G/C may be more susceptible to the development of PD. Further studies are needed to replicate the associations that we observed.