Background Longitudinal studies of illness progression in patients with major depressive disorder (MDD) indicate that the onset of subsequent depressive episodes becomes increasingly decoupled from external stressors. A possible mechanism underlying this phenomenon is that multiple episodes induce long-lasting neurobiological changes that confer increased risk for recurrence. Prior morphometric studies have frequently reported volumetric reductions in patients with MDD—especially in medial prefrontal cortex (mPFC) and the hippocampus—but few studies have investigated whether these changes are exacerbated by prior episodes. Methods In a sample of 103 medication-free patients with depression and control subjects with no history of depression, structural magnetic resonance imaging was performed to examine relationships between number of prior episodes, current stress, hippocampal subfield volume and cortical thickness. Volumetric analyses of the hippocampus were performed using a recently validated subfield segmentation approach, and cortical thickness estimates were obtained using vertex-based methods. Participants were grouped on the basis of the number of prior depressive episodes and current depressive diagnosis. Results Number of prior episodes was associated with both lower reported stress levels and reduced volume in the dentate gyrus. Cortical thinning of the left mPFC was associated with a greater number of prior depressive episodes but not current depressive diagnosis. Conclusions Collectively, these findings are consistent with preclinical models suggesting that the dentate gyrus and mPFC are especially vulnerable to stress exposure and provide evidence for morphometric changes that are consistent with stress-sensitization models of recurrence in MDD.

Illness Progression, Recent Stress, and Morphometry of Hippocampal Subfields and Medial Prefrontal Cortex in Major Depression

Using behavioral, pharmacological, and molecular methods, lots of studies reveal that depression is closely related to the abnormal neural plasticity processes occurring in the prefrontal cortex and limbic system such as the hippocampus and amygdala. Meanwhile, functions of the brain-derived neurotrophic factor (BDNF) and the other neurotrophins in the pathogenesis of depression are well known. The maladaptive neuroplastic in depression may be related to alterations in the levels of neurotrophic factors, which play a central role in plasticity. Enhancement of neurotrophic factors signaling has great potential in therapy for depression. This review highlights the relevance of neurotrophic factors mediated neural plasticity and pathophysiology of depression. These studies reviewed here may suggest new possible targets for antidepressant drugs such as neurotrophins, their receptors, and relevant signaling pathways, and agents facilitating the activation of gene expression and increasing the transcription of neurotrophic factors in the brain.

The Role of BDNF on Neural Plasticity in Depression.

Chronic pain is a condition in which pain progresses from an acute to chronic state and persists beyond the healing process. Chronic pain impairs function and decreases patients’ quality of life. In recent years, efforts have been made to deepen our understanding of chronic pain and to develop better treatments to alleviate chronic pain. In this review, we summarize the results of previous studies, focusing on the mechanisms underlying chronic pain development and the identification of neural areas related to chronic pain. We review the association between chronic pain and negative affective states. Further, we describe the structural and functional changes in brain structures that accompany the chronification of pain and discuss various neurotransmitter families involved. Our review aims to provide guidance for the development of future therapeutic approaches that could be used in the management of chronic pain.

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Chronic Pain: Structural and Functional Changes in Brain Structures and Associated Negative Affective States.

Accumulating evidence demonstrates that the gut microbiota affects brain function and behavior, including depressive behavior. Antidepressants are the main drugs used for treatment of depression. We hypothesized that antidepressant treatment could modify gut microbiota which can partially mediate their antidepressant effects. Mice were chronically treated with one of five antidepressants (fluoxetine, escitalopram, venlafaxine, duloxetine or desipramine), and gut microbiota was analyzed, using 16s rRNA gene sequencing. After characterization of differences in the microbiota, chosen bacterial species were supplemented to vehicle and antidepressant-treated mice, and depressive-like behavior was assessed to determine bacterial effects. RNA-seq analysis was performed to determine effects of bacterial treatment in the brain. Antidepressants reduced richness and increased beta diversity of gut bacteria, compared to controls. At the genus level, antidepressants reduced abundances of Ruminococcus, Adlercreutzia, and an unclassified Alphaproteobacteria. To examine implications of the dysregulated bacteria, we chose one of antidepressants (duloxetine) and investigated if its antidepressive effects can be attenuated by simultaneous treatment with Ruminococcus flavefaciens or Adlercreutzia equolifaciens. Supplementation with R. flavefaciens diminished duloxetine-induced decrease in depressive-like behavior, while A. equolifaciens had no such effect. R. flavefaciens treatment induced changes in cortical gene expression, up-regulating genes involved in mitochondrial oxidative phosphorylation, while down-regulating genes involved in neuronal plasticity. Our results demonstrate that various types of antidepressants alter gut microbiota composition, and further implicate a role for R. flavefaciens in alleviating depressive-like behavior. Moreover, R. flavefaciens affects gene networks in the brain, suggesting a mechanism for microbial regulation of antidepressant treatment efficiency.

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Antidepressants affect gut microbiota and Ruminococcus flavefaciens is able to abolish their effects on depressive-like behavior

Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders.

Neural plasticity, a fundamental mechanism of neuronal adaptation, is disrupted in depression. The changes in neural plasticity induced by stress and other negative stimuli play a significant role in the onset and development of depression. Antidepressant treatments have also been found to exert their antidepressant effects through regulatory effects on neural plasticity. However, the detailed mechanisms of neural plasticity in depression still remain unclear. Therefore, in this review, we summarize the recent literature to elaborate the possible mechanistic role of neural plasticity in depression. Taken together, these findings may pave the way for future progress in neural plasticity studies.

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The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex.

// Tongtong Ge 1, * , Wei Yang 1, * , Jie Fan 1 and Bingjin Li 1 1 Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, PR China * These authors contributed equally to this work Correspondence to: Bingjin Li, email: libingjin@jlueducn Keywords: ghrelin, epilepsy, hippocampus, memory, neuroprotection Received: March 08, 2017      Accepted: May 22, 2017      Published: June 02, 2017 ABSTRACT Ghrelin, an orexigenic peptide synthesized by endocrine cells of the gastric mucosa, plays a major role in inhibiting seizures However, the underlying mechanism of ghrelin’s anticonvulsant action is still unclear Nowadays, there are considerable evidences showing that ghrelin is implicated in various neurophysiological processes, including learning and memory, neuroprotection, neurogenesis, and inflammatory effects In this review, we will summarize the effects of ghrelin on epilepsy It may provide a comprehensive picture of the role of ghrelin in epilepsy

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Preclinical evidence of ghrelin as a therapeutic target in epilepsy

// Xue Feng Wang 1 , Tong Tong Ge 1 , Jie Fan 1 , Wei Yang 1 and Ran Ji Cui 1 1 Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, Second Hospital of Jilin University, Changchun, People’s Republic of China Correspondence to: Wei Yang, email: wyang2002@jlu.edu.cn Ran Ji Cui, email: cuiranji@jlu.edu.cn Keywords: substance P, epilepsy, inflammation, neuron Received: April 03, 2017      Accepted: August 17, 2017      Published: September 01, 2017 ABSTRACT A range of evidence implicates the neuropeptide substance P (SP), a member of the tachykinin family, in emotional behavior, anxiety, pain, and inflammation. Recently, SP has been implicated in susceptibility to seizures, for which a potential proconvulsant role was indicated. Indeed, antagonists of a specific SP receptor, neurokinin-1 receptor, were found to attenuate kainic acid (KA)-induced seizure activity. However, detailed mechanisms of SP regulation in epilepsy remain obscure. In this review, we summarize the present literature to expound the role of SP in epilepsy, and provide hypotheses for potential mechanisms.

Wei Yang

Papers

The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex.

Preclinical evidence of ghrelin as a therapeutic target in epilepsy

The role of substance P in epilepsy and seizure disorders.