No abstract

Rationale Abnormalities in Toll-like receptor (TLR) expression in depression have been inferred in part from observed increases in TLR4 levels in peripheral blood mononuclear cells (PBMCs) and postmortem brains of depressed and suicidal patients. Our previous study found differences in the TLR expression in PBMCs between healthy controls and patients with major depressive disorder. Normalization of increased TLR4 in PBMCs by cognitive behavior psychotherapy has been reported. However, the effects of antidepressants remain unknown. Objectives Changes in TLR1-9 expression levels of PBMCs were examined in 56 patients with MDD. The 17-item Hamilton Depression Rating Scale (HAMD-17) and mRNA expression levels of TLRs were assessed in parallel with a housekeeping gene using qRT-PCR before and after treatment with antidepressants. Results TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9 were expressed at elevated levels in patients with MDD and were significantly decreased by treatment with antidepressants for 4 weeks. Antidepressant treatment completely normalized TLR3, TLR5, TLR7, TLR8, and TLR9 levels, whereas TLR1, TLR2, TLR4, and TLR6 were decreased to below normal levels. A subgroup analysis found that only TLR3 was significantly higher at baseline in the nonremission group. In addition, a multiple linear regression analysis revealed that only low TLR3 before treatment predicted improvement in HAMD-17 scores. Conclusions These findings suggest that antidepressant treatment exerts anti-inflammatory effects in patients with MDD and identify TLR profiles as a predictor of response to antidepressant therapy. Further studies investigating the effects of manipulating individual TLRs on depression are needed to fully elucidate the underlying mechanism.

Inflammation and abnormalities in Toll-like receptor (TLR) expression and activation have been linked to major depressive disorder (MDD). However, negative regulators of TLR pathways have not been previously investigated in this context. Here, we sought to investigate the association of depression severity, measured by the 17-item Hamilton Depression Rating Scale (HAMD-17), with mRNA expression levels of negative regulators of the TLR pathway, including SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2 and TNFAIP3, in peripheral blood mononuclear cells (PBMCs) from 100 patients with MDD and 53 healthy controls, before and after treatment with antidepressants. Positive regulators of the TLR4 pathway, including Pellino 1, TRAF6 and IRAK1, were also investigated. Among all patients, MyD88s, and TNFAIP3 mRNAs were expressed at lower levels in PBMCs from patients with MDD. Multiple linear regression analyses revealed that TNFAIP3 mRNA expression before treatment was inversely correlated with severity of depression and effectively predicted improvement in HAMD-17 scores. Among 79 treatment-completers, only TNFAIP3 mRNA was significantly increased by treatment with antidepressants for 4 weeks. Treatment of human monocytes (THP-1) and mouse microglia (SIM-A9) cell lines with fluoxetine significantly increased TNFAIP3 mRNA expression and suppressed IL-6 levels. The suppressive effect of fluoxetine on IL-6 was attenuated by knockdown of TNFAIP3 expression. These findings suggest that both dysfunction of the negative regulatory system in patients with MDD and antidepressant treatment exert anti-inflammatory effects, at least in part through increased expression of the TNFAIP3 gene. They also indicate that modulating expression of the TNFAIP3 gene to rebalance TLR-mediated inflammatory signaling may be potential therapeutic strategy for treating MDD.

Chronic inflammation and abnormalities in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Our previous work reported that impaired negative regulators for the TLR pathways are associated with MDD. This study aimed to assess the association between the severity of depression and the intracellular microRNAs that regulate TLR4 signaling in both peripheral blood mononuclear cells (PBMCs) and monocytes from MDD patients. The severity of MDD before and after antidepressant treatment was determined by the 17-item Hamilton Depression Rating Scale, and quantitative RT-PCR was used to measure the levels of intracellular regulatory microRNAs, including let-7e, miR-21-5p miR-145, miR-223, miR-146a, and miR-155, in PBMCs and monocytes isolated from 43 healthy controls and 84 patients with MDD before and after treatment with antidepressants. Assays of PBMCs showed that the levels of let-7e, miR-146a, and miR-155 were lower in MDD patients than in healthy controls and were significantly higher after than before treatment in the 69 patients who completed treatment with antidepressants for four weeks. Levels of miR-146a and miR-155 in monocytes were lower in MDD patients than in controls and were increased in the former after antidepressant treatment. Multiple linear regression analyses found that let-7e and miR-146a expression before treatment was inversely correlated with severity of depression, whereas miR-155 before treatment was directly correlated with severity of depression. These findings suggest that intracellular regulatory microRNAs which regulate TLR4 signaling are aberrantly expressed in patients with MDD and that these levels are ameliorated by antidepressant treatment.

We have proved that a modified strategy (ie, lorazepam intramuscular injection [IMI] or diazepam intravenous drip [IVD] if lorazepam IMI fails) can rapidly relieve catatonic features in patients with schizophrenia. During a period of 3 years, we identified 7 major depressive patients with catatonic features in the emergency unit of a general hospital. The patients were treated with lorazepam IMI (dose, 2 mg/mL.per ampule) once or twice during the first 2 hours. If lorazepam IMI failed, diazepam IVD (dose, 10 mg/2 mL.per ampule) in 500 mL normal saline every 8 hours for 1 day would be administered. The total complete remission rate to lorazepam IMI within 2 hours was 6 (85.7%) per 7 patients, and the total complete remission rate to benzodiazepines (lorazepam IMI and diazepam IVD) within 1 day was 7 (100%) of all 7 patients. These results highly suggest that this modified strategy can also rapidly relieve catatonic features in major depression within 1 day and attain a high complete remission rate, even without electroconvulsive therapy.

ObjectiveThe lorazepam-diazepam protocol had been proved to rapidly and effectively relieve catatonia in patients with schizophrenia or mood disorder. This study aims to investigate the efficacy of lorazepam-diazepam protocol in catatonia due to general medical conditions (GMC) and substance.MethodPatients with catatonia that required psychiatric intervention in various settings of a medical center were included. The lorazepam-diazepam protocol had been used to treat the catatonia due to GMC or substance according to DSM-IV criteria. The treatment response had been assessed by two psychiatrists.ResultsEighteen (85.7%) of 21 catatonic patients due to GMC or substance became free of catatonia after the lorazepam-diazepam protocol. Five (23.8%) of the 21 patients had passed away with various causes of death and wide range of time periods after catatonia.ConclusionOur results showed that the lorazepam-diazepam protocol could rapidly and effectively relieve catatonia due to GMC and substance.

Aim:In this study, we investigated serum protein levels of brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) in patients with bipolar disorder. Methods:Over a 2-year period, 26 patients with bipolar I disorder (manic episode) and 56 healthy controls were recruited. The Young Mania Rating Scale scores of patients with bipolar mania were >26. Serum BDNF and TrkB protein levels were measured with ELISA kits. Results: Using ANCOVA with age adjustment, we found that there were no significant differences in serum BDNF protein levels between patients with bipolar mania and healthy controls (p = 0.582). In contrast, the serum TrkB protein level was significantly higher in bipolar mania patients than in healthy controls (p = 0.001), especially in women (p = 0.001). Of 26 patients with bipolar mania, 21 underwent a second measurement of serum BDNF and TrkB protein levels after a 4-week treatment with mood stabilizers. There were no significant changes in serum BDNF or TrkB protein levels. Conclusion:These findings suggest that serum TrkB protein levels may play an important role in the psychopathology of bipolar mania. However, a larger sample size is needed to confirm these results.

No abstract