4.4 Review

Recent Advances in the Early Intervention in Schizophrenia: Future Direction from Preclinical Findings

Journal

CURRENT PSYCHIATRY REPORTS
Volume 21, Issue 8, Pages -

Publisher

SPRINGER
DOI: 10.1007/s11920-019-1063-7

Keywords

D-Serine; Keap1-Nrf2; Sodium benzoate; Soluble epoxide hydrolase; Sulforaphane; TrkB agonist

Categories

Funding

  1. Japan Society for the Promotion of Science (JSPS) KAKENHI [17H042431]
  2. Japan Agency for Medical Research and Development [JP19dm0107119]

Ask authors/readers for more resources

Purpose of ReviewIn the past decade, there has been increasing interest in the potential benefit of early intervention in schizophrenia. Patients with schizophrenia show cognitive impairment for several years preceding the onset of psychosis. The author discusses the recent topics on prevention of schizophrenia.Recent FindingsPreclinical findings suggest that maternal immune activation (MIA) produces cognitive deficits as a prodromal symptom in juvenile offspring in rodents. Treatment with anti-inflammatory compounds, such as D-serine, 7,8-dihydroxyflavone (a TrkB agonist), sulforaphane (or its precursor glucoraphanin), and TPPU (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea: a soluble epoxide hydrolase inhibitor), during adolescence might prevent the onset of behavioral abnormalities and parvalbumin immunoreactivity in the medial prefrontal cortex of adult offspring after MIA.SummaryBased on the role of inflammation and cognitive impairment in the prodromal state, early intervention using anti-inflammatory compounds (i.e., D-serine, sodium benzoate, TrkB agonist, Nrf2 agonist, soluble epoxide hydrolase inhibitor) may reduce the risk of subsequent transition to schizophrenia.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.4
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Medicine, Research & Experimental

The soluble epoxide hydrolase inhibitor TPPU improves comorbidity of chronic pain and depression via the AHR and TSPO signaling

Ailin Luo, Zifeng Wu, Shan Li, Cindy B. McReynolds, Di Wang, Hanyu Liu, Chaoli Huang, Teng He, Xinying Zhang, Yuanyuan Wang, Cunming Liu, Bruce D. Hammock, Kenji Hashimoto, Chun Yang

Summary: This study investigated the relationship between chronic pain and depression and the potential benefits of inhibiting soluble epoxide hydrolase (sEH) signaling. The results showed that sEH expression was associated with pain and depression behaviors, and the sEH inhibitor TPPU improved the symptoms of both. The therapeutic effects of TPPU were mediated through the AHR and TSPO signaling pathways.

JOURNAL OF TRANSLATIONAL MEDICINE (2023)

Article Neurosciences

Sex-Specific Differences in the Transcriptome of the Human Dorsolateral Prefrontal Cortex in Schizophrenia

Zhiqian Yu, Kazuko Ueno, Ryo Funayama, Mai Sakai, Naoki Nariai, Kaname Kojima, Yoshie Kikuchi, Xue Li, Chiaki Ono, Junpei Kanatani, Jiro Ono, Kazuya Iwamoto, Kenji Hashimoto, Kengo Kinoshita, Keiko Nakayama, Masao Nagasaki, Hiroaki Tomita

Summary: This study investigated the transcriptional profiles in the dorsolateral prefrontal cortex (DLPFC) to understand the clinical and biological differences of schizophrenia between males and females. The results showed that females with schizophrenia had more significantly changed genes compared to males, and these changes were mainly related to mitochondrial, ATP- and metal ion-binding relevant biological processes. The differentially expressed genes related to schizophrenia in females were involved in midbrain dopaminergic and GABA-ergic neurons and microglia. Additionally, analysis of a murine model revealed that the methylation and transcriptional expression of the ACSBG1 locus potentially impact the sex differences in gene transcription.

MOLECULAR NEUROBIOLOGY (2023)

Review Biochemistry & Molecular Biology

Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies

Jie Guo, Di Qiu, Han-wen Gu, Xing-ming Wang, Kenji Hashimoto, Guang-fen Zhang, Jian-jun Yang

Summary: The perioperative administration of ketamine reduces postoperative depression and pain scores but increases the risk of adverse effects.

MOLECULAR PSYCHIATRY (2023)

Article Neurosciences

Key role of the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve in demyelination of the cuprizone-treated mouse brain

Xingming Wang, Akifumi Eguchi, Yong Yang, Lijia Chang, Xiayun Wan, Jiajing Shan, Youge Qu, Li Ma, Chisato Mori, Jianjun Yang, Kenji Hashimoto

Summary: Multiple sclerosis (MS) is a common demyelinating disease that affects the central nervous system. This study investigated the effects of subdiaphragmatic vagotomy (SDV) on demyelination in cuprizone (CPZ)-treated mice and found that SDV significantly improved demyelination and microglial activation in the brain. Analysis of gut microbiota composition and blood metabolites revealed that SDV also improved the abnormal levels in CPZ-treated mice. These findings suggest a link between the gut microbiota-brain axis and demyelination in the brain.

NEUROBIOLOGY OF DISEASE (2023)

Correction Neurosciences

Key role of the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve in demyelination of cuprizone-treated mouse brain (vol 176, 105961, 2023)

X. Wang, A. Eguchi, Y. Yang, L. Chang, X. Wan, J. Shan, Y. Qu, L. Ma, C. Mori, J. Yang, K. Hashimoto

NEUROBIOLOGY OF DISEASE (2023)

Article Psychiatry

Repeated use of 3,4-methylenedioxymethamphetamine is associated with the resilience in mice after chronic social defeat stress: A role of gut-microbiota-brain axis

Youge Qu, Akifumi Eguchi, Xiayun Wan, Li Ma, Lijia Chang, Jiajing Shan, Yong Yang, Chisato Mori, Kenji Hashimoto

Summary: 3,4-Methylenedioxymethamphetamine (MDMA), the most widely used illicit compound worldwide, may contribute to stress resilience in mice subjected to chronic social defeat stress (CSDS) through the gut-microbiota-brain axis. The study found that MDMA treatment prevented the negative effects of CSDS, such as splenomegaly, anhedonia-like phenotype, and increased interleukin-6 (IL-6) levels in the mice. Gut microbiome analysis revealed differences between the saline + CSDS group and the MDMA + CSDS group, while metabolomics analysis showed altered plasma levels of N-epsilon-methyl-L-lysine in the saline + CSDS group compared to the control and MDMA + CSDS groups.

PSYCHIATRY RESEARCH (2023)

Article Clinical Neurology

Risk of esketamine anesthesia on the emergence delirium in preschool children after minor surgery: a prospective observational clinical study

Sai Chen, Jin-Jin Yang, Yue Zhang, Lei Lei, Di Qiu, Hui-Min Lv, Zhen-Tao Sun, Kenji Hashimoto, Jian-Jun Yang

Summary: This study investigated the effects of a single-dose of esketamine during anesthesia induction on emergence delirium (ED) in preschool children after minor surgery. The study found that the use of esketamine was associated with a higher incidence and score of ED, as well as a longer post-anesthesia care unit stay. However, there were no significant differences in other outcomes between the two groups. Therefore, the use of esketamine in preschool children for minor surgery should be noticed.

EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE (2023)

Review Clinical Neurology

Arketamine for cognitive impairment in psychiatric disorders

Kenji Hashimoto

Summary: Cognitive impairment is a common feature in various psychiatric disorders, and current therapeutic drugs do not effectively improve it. However, (R,S)-ketamine, particularly (R)-ketamine, has shown potential in improving cognitive impairment. The gut-microbiome-brain axis may also play a role in cognitive impairment in psychiatric disorders.

EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE (2023)

Editorial Material Neurosciences

Ketamine and its metabolites: Potential as novel treatments for depression

Kenji Hashimoto, Shigeyuki Chaki

NEUROPHARMACOLOGY (2023)

Article Neurosciences

A role of GABAA receptor α1 subunit in the hippocampus for rapid-acting antidepressant-like effects of ketamine

Xiao-Hui Tang, Yu-Gang Diao, Zhuo-Yu Ren, Yan-Yu Zang, Guang-Fen Zhang, Xing-Ming Wang, Gui-Fang Duan, Jin-Chun Shen, Kenji Hashimoto, Zhi-Qiang Zhou, Jian-Jun Yang

Summary: Mouse models of depression-like behavior showed decreased levels of GABA and increased levels of glutamate in the hippocampus. Ketamine treatment reversed these alterations by increasing GABA levels and decreasing glutamate levels. These effects were mediated by changes in enzymes and transporters on GABAergic neurons and astrocytes.

NEUROPHARMACOLOGY (2023)

Article Neurosciences

Beneficial effects of arketamine on the reduced bone mineral density in susceptible mice after chronic social defeat stress: Role of the gut-microbiota-bone-brain axis

Xiayun Wan, Akifumi Eguchi, Lijia Chang, Chisato Mori, Kenji Hashimoto

Summary: Patients with depression often have reduced bone mineral density. The new antidepressant arketamine has been shown to improve this reduction in mice. This study investigates the potential role of the gut microbiota and its metabolites in the beneficial effects of arketamine on behavioral and bone density changes in mice with chronic social defeat stress.

NEUROPHARMACOLOGY (2023)

Article Neurosciences

Mesenchymal stem-cell-derived microvesicles ameliorate MPTP-induced neurotoxicity in mice: a role of the gut-microbiota-brain axis

Yaoyu Pu, Qiuhong Wu, Qiuping Zhang, Tianwen Huang, Ji Wen, Long Wei, Kenji Hashimoto, Yi Liu

Summary: This study aimed to investigate the effect of mesenchymal stem-cell-derived microvesicles (MSC-MVs) in treating Parkinson's disease (PD). The results showed that single administration of MSC-MVs could alleviate the reduction of dopamine transporter and tyrosine hydroxylase expressions in the striatum and substantia nigra (SNr) of mice after MPTP injection. MSC-MVs also restored the abnormal gut microbiota composition induced by MPTP. Therefore, MSC-MVs have a new therapeutic potential for neurological disorders such as PD.

PSYCHOPHARMACOLOGY (2023)

Review Biochemistry & Molecular Biology

Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein-Barr virus and the gut-brain axis

Kenji Hashimoto

Summary: The COVID-19 pandemic caused by SARS-CoV-2 infection has resulted in various health issues, including persistent neurological and psychiatric symptoms known as long COVID or brain fog. The virus has been detected in the brains of patients who died from COVID-19, and Epstein-Barr virus reactivation and changes in the microbiome may contribute to long COVID symptoms. This article discusses the detrimental effects of COVID-19 on the brain and the biological mechanisms underlying long COVID, as well as potential therapeutic approaches targeting the gut-brain axis.

MOLECULAR PSYCHIATRY (2023)

Review Biochemistry & Molecular Biology

Emerging role of the host microbiome in neuropsychiatric disorders: overview and future directions

Kenji Hashimoto

Summary: The human body contains a diverse ecosystem of microorganisms, known as the microbiota, which includes bacteria, viruses, and fungi. Current research is focusing on the potential association between the microbiota and neuropsychiatric disorders. While the gut microbiota has received particular attention, the microbiota in other body tissues also influences the development and progression of these disorders. This article provides an overview of the role of the host microbiota in neuropsychiatric disorders and explores future research directions.

MOLECULAR PSYCHIATRY (2023)

Article Neurosciences

Infusions of beta-hydroxybutyrate, an endogenous NLRP3 inflammasome inhibitor, produce antidepressant-like effects on learned helplessness rats through BDNF-TrkB signaling and AMPA receptor activation, and strengthen learning ability

Yukihiko Shirayama, Masaaki Iwata, Kanako Miyano, Yuki Hirose, Yasunori Oda, Yuko Fujita, Kenji Hashimoto

Summary: Beta-hydroxybutyrate (BHB) has shown antidepressant-like effects in a rat model of depression. It activates the BDNF-TrkB signaling pathway and AMPA receptors, and is associated with the prefrontal cortex, hippocampus, and basolateral region of amygdala.

BRAIN RESEARCH (2023)

No Data Available