The mechanism of action of electroconvulsive therapy (ECT) has not been elucidated yet, but even for refractory depression, 80% is an effective treatment showing improvement. However, the rejection reaction accompanying the history of abuse first preceded, and the discussion on the improvement of the procedure has been postponed. In Japan, pulse wave therapy equipment has been approved in 2002, gradually it is becoming an era where the quality of treatment is questioned also in ECT. Quality of treatment includes not only effects but also safety and ethical considerations, but this time we particularly influence the therapeutic effect 1. Adaptable disease, 2. Tapering off anticonvulsant drugs, 3. Setting of stimulation dose, 4. Evaluation of seizure wave, 5. Seizure Augmentation, 6. Postoperative rounds, 7. Continuing and maintaining ECT will be presented as a review article and we will introduce our approach at this hospital.

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Stimulus parameters in electroconvulsive therapy (ECT) are believed to have unique neurobiological effects and affect its clinical outcomes such as efficacy, seizure threshold, and cognitive impairment. The author argued the significance of optimizing stimulus parameters including pulse width in electroconvulsive therapy and overviewed recent findings regarding right unilateral ultrabrief pulse ECT. The author also proposed that adjustment of pulse width can be an augmentation strategy in case of missed or inadequate seizures.

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Non‐convulsive procedure is a mainstay of current electroconvulsive therapy (ECT) , and anesthesia is required for the procedure. It is generally accepted that anesthetics not only alleviate the fears of patients but also affect the efficacy and tolerability of ECT, or convulsive seizures to a certain extent. In Japan, propofol and thiopental are widely used in ECT, and ultra‐short‐acting analgesic remifentanil concomitant with intravenous anesthetics, and intravenous anesthetic such as ketamine have been used frequently in recent years. This article reviews the effects of these anesthetics on the efficacy of ECT and convulsive seizures.

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Electroconvulsive therapy (ECT) has been one of the most effective psychiatric treatments particularly for severe depression, but its mechanisms of action remain unknown. Brain imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) have been used to elucidate the mechanisms of action of ECT in humans. Takano et al. examined acute effects of ECT on cerebral blood flow (CBF) using PET with H₂¹⁵O and demonstrated that during ECT, CBF increased extensively, particularly in the brainstem and diencephalon during generalized seizures, suggesting the importance of these regions for therapeutic efficacy and their association with seizure generalization. Soon after ECT, CBF decreased in the anterior cingulate and medial frontal cortex, indicating postictal suppression, reportedly related to the efficacy of ECT. As for structural MRI studies, meta-analyses of volumetric MRI have shown an increased hippocampal volume after a course of ECT treatments, reflecting the neurotrophic effect of ECT. Finally, magnetic seizure therapy (MST) , which is another convulsive therapy, has recently been introduced as a new therapeutic option, and it has comparable efficacy and fewer cognitive side effects than ECT. MST also needs to be investigated using brain imaging techniques to reveal its mechanisms of action.

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The neuroplasticity hypothesis is becoming more common in the pathology of depression, however the mechanisms by which stress causes atrophy of neuronal processes and decreases the synapse number is unknown. Here we showed that psychological stress is sensed by the innate immune system in the brain via NLRP3 inflammasome, which in turn releases pro-inflammatory cytokines. The NLRP3 inflammasome has become the focus of a wide range of medical research areas because it is a critical sensor for diverse diseases. Thus, it is critical for the development of new pharmacotherapeutic approaches that target neuro-inflammation in depression.

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Moderate stress evokes adaptive stress responses. On the other hand, prolonged and excessive stress is a risk factor of psychiatric disorders. However, the mechanism underlying how stress induce emotional changes remains unknown. Since recent studies established the crucial roles of inflammation-like responses in stress-induced emotional changes, inflammation-like responses in both brain and periphery have been studied. In the brain, inflammation-related molecules is involved in repeated stress-induced suppression of dopaminergic system in the medial prefrontal cortex, and repeated stress activates microglia to produce inflammatory cytokines. In the periphery, stress-induced endocrine responses activate myeloid cells to produce inflammatory cytokines, whereas stress-induced sympathetic activation increases the number of neutrophils and monocytes in the blood. Furthermore, it is suggested that these peripheral changes affect microglial activation. These findings imply vicious cycle of inflammation between the brain and periphery and have led us to propose the development of novel anti-depressant drugs targeting on stress-induced inflammation.

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NADPH oxidase is a source of reactive oxygen species (ROS) that have been implicated in the pathogenesis of various neurological disorders. We here demonstrated the involvement of a non-phagocytic type of NADPH oxidase, NOX1, in the hallmarks of major depressive disorders, including behavioral, biochemical and anatomical changes in mice. Oxidation of NMDA receptor 1 (NR1) by NOX1-derived ROS was depicted in the prefrontal cortex (PFC) , which could be causally linked to down-regulation of BDNF, promoting depressive-like behaviors. Given that NOX1 was up-regulated in the ventral tegmental area but not in PFC, mesocortical projections may play a crucial role in NOX1-dependent depressive-like behaviors. Our study present the potential molecular mechanism underlying the development of major depression through NOX1-induced oxidation of NR1 and epigenetic modification of the bdnf gene.

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This paper reviewed the evidence for the efficacy of omega‐3 fatty acids against depression and depressive symptoms, focusing on anti‐inflammatory effect. Inflammation is one of the potential pathogenesis of depression. Omega‐3 fatty acids, especially eicosapentaenoic acid (EPA) , have anti‐inflammatory effect. A number of meta‐analyses of randomized controlled trials (RCTs) support the positive effects of EPA supplementation in treating depression and reducing depressive symptoms. Thus, anti‐inflammatory effect is believed to be one of the mechanisms for anti‐depressant action of EPA. However, the amount of omega‐3 fatty acids and intervention duration varied across previous RCTs. Moreover, there is no clear evidence on the optimal amount of supplemental omega‐3 fatty acids for different countries with different levels of fish consumption and there are especially few available evidences in countries, such as in Japan, where people consume much more fish than in other countries..
Nutritional approaches for depressive symptoms could be widely applicable to various populations including pregnant women and children due to potentially fewer side effects as compared with pharmaceutical approaches. Further studies should explore the possibilities in practical use of nutritional approaches in prevention and treatment of depression.

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Microglia, immune cells in the brain, has recently been highlighted to understand the pathophysiology of mood disorders especially depression. Herein, we introduced our novel translational research system of mood disorders using [1] directly induced microglia‐like (iMG) cells, which can be produced from human peripheral monocytes within two weeks with two cytokines ; GM‐CSF and IL‐34, and [2] human plasma/serum analysis such as metabolomics.

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