Recently, accumulated evidence has indicated a role of inflammation in the pathogenesis of major depressive disorder (MDD). Therefore, we evaluated the relationship between white matter integrity and serum cytokine levels during the first depressive episode in drug-naive MDD patients, using a tract-based spatial statistics (TBSS) method. A total of 35 drug-naive MDD patients with a first depressive episode and 35 healthy subjects (HS) underwent diffusion tensor imaging, and an analysis was conducted using TBSS. We measured serum cytokine levels (interleukin [IL]-1β, IL-6, interferon-γ, and tumor necrosis factor-α). Fractional anisotropy (FA) values of the bilateral inferior fronto-occipital fasciculus (IFOF) and genu of the corpus callosum in MDD patients were decreased significantly to the HS (p < 0.05 with family-wise error [FWE] correction) and were significantly inversely correlated with the IL-1β levels (p < 0.05, with FWE correction). No regions showed a correlation between FA values and other serum cytokine levels. Our results suggested that the microstructural changes in IFOF and genu of the corpus callosum are associated with the high IL-1β levels in the early stage of MDD.

These results suggest that the plasma levels of IL-6 reflect the severity of MDD and that plasma IL-6 levels might be another biological-state marker for the depressive state. In addition, the 5-HTTLPR polymorphism might be independent of plasma IL-6 levels.

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ObjectiveTo study the effects of treatment with atypical antipsychotic drugs on brain levels of glutamate plus glutamine in early-stage first-episode schizophrenia.ParticipantsSixteen patients (eight males, eight females; aged 30 ± 11 years) completed the study.MethodsWe used administered 6 months of atypical antipsychotic drugs and used proton magnetic resonance spectroscopy to evaluate the results.ResultsWe found that the administration of atypical antipsychotic drugs for 6 months decreased the glutamate plus glutamine/creatine ratio in the frontal lobe. These results suggest that the administration of atypical antipsychotic drugs for at least 6 months decreased glutamatergic neurotransmissions in the frontal lobe in early-stage first-episode schizophrenia, but there was no difference in frontal-lobe levels between patients and control subjects before administration.ConclusionTaking these findings into account, the glutamatergic and GABAergic neurons are implicated in early-stage first-episode schizophrenia, but in complex ways.

In the early stage of MDD, the thickness of the lateral orbitofrontal cortex was significantly reduced, and also showed a significant inverse correlation with the serum cortisol levels. Since the lateral orbitofrontal cortex contains a high concentration of glucocorticoid receptor, glucocorticoid receptor-mediated signaling transductions could contribute to neurotoxicity, which might occur when there are high cortisol levels in patients with MDD.