In the 2019 Global Burden of Disease Study, the number of schizophrenia cases was reported to have increased from 14.2 million in 1990 to 23.6 million in 2019. Furthermore, schizophrenia has contributed to 12.2% disability-adjusted life-years globally.¹ The main symptomatic dimensions of schizophrenia included positive, cognitive, and negative symptoms.² Although antipsychotic drugs are relatively effective in mitigating positive symptoms of schizophrenia, their efficacy is limited for the treatment of the negative symptoms of the illness.² Evidence indicates that the negative symptoms play a key detrimental role in overall disability and quality of life of people with schizophrenia.²

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that modulates neuroplasticity in the brain, and is one of the most widely investigated molecule in psychiatric disorders. The researches of BDNF emcompassed the advance of investigative techniques of past decades. BDNF researches ranged from protein quantilization, to RNA expression measurements, to DNA sequencing, and lately but not lastly, epigenetic studies. In this review, we will briefly address findings on BDNF protein levels, mRNA expression, Val66Met polymorphism, and epigenetic modifications, in schizophrenia, major depressive disorder (MDD), and bipolar disorder.

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.

Abstract  Several studies have discussed the relationships between T‐helper 1 (Th1) or Th2 cytokines and major depression. The aim of the present study was to investigate the relationships between Th1/Th2 cytokine balance and clinical phenotypes of acute‐phase major depression. A total of 82 subjects including 42 patients with major depressive disorder and 40 healthy controls were recruited. Serum cytokine levels of interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α) and IL‐10 were examined. Using ancova with age and body mass index (BMI) adjustments, there were no significant differences in serum IL‐1β, TNF‐α, and IL‐10 levels between patients with major depressive disorder and healthy controls. However, using ancova with BMI adjustment only, the results showed that patients with major depressive disorder had significantly higher TNF‐α levels than control subjects. In addition, using ancova with age and BMI adjustments, significantly higher serum IL‐1β level and IL‐1β/IL‐10 ratio were noted in patients with melancholic features than patients with non‐melancholic features. However, there were no significant differences in serum IL‐1β, TNF‐α and IL‐10 levels between patients with and without suicide attempt. In conclusion, serum TNF‐α, IL‐1β level and IL‐1β/IL‐10 ratio might play an important role in the psychopathology of acute‐phase major depressive disorder.