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Ketamine for Treatment Resistant Depression

Ketamine for Treatment Resistant Depression Book
Author : Gustavo H. Vazquez,Carlos A. Zarate,Elisa Brietzke
Publisher : Academic Press
Release : 2020-10-15
ISBN : 0128210338
Language : En, Es, Fr & De

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Book Description :

Ketamine for Treatment-Resistant Depression: Neurobiology and Applications provides a simple, evidence-based overview for neuropsychiatrists and translational researchers on this medication, its mechanisms of actions, eligibility of patients for treatment, and the preparation and implementation of ketamine clinics. Provides efficacy research on ketamine as a treatment for depression Identifies best practices for clinical use, both long-term and acute Discusses the molecular mechanisms and neurobiology of action

Ketamine for Treatment Resistant Depression

Ketamine for Treatment Resistant Depression Book
Author : Sanjay J. Mathew,Carlos A. Zarate, Jr.
Publisher : Adis
Release : 2016-10-05
ISBN : 9783319429236
Language : En, Es, Fr & De

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Book Description :

This book brings together an international group of clinicians and researchers from a broad swath of inter-related disciplines to offer the most up-to-date information about clinical and preclinical research into ketamine and second-generation “ketamine-like” fast-acting antidepressants. Currently available antidepressant medications act through monoaminergic systems, are ineffective for many individuals suffering from depression, and are associated with a delayed onset of peak efficacy of several months. The unexpected emergence of ketamine, an anesthetic N-methyl-D-aspartate (NMDA) receptor antagonist, as a rapid-acting antidepressant has reinvigorated CNS drug discovery research and catalyzed investigation in patient populations historically ignored in antidepressant drug development programs, particularly treatment-resistant patients and those with suicidality. Recent industry and academic research efforts have coalesced to explore NMDA receptor and glutamatergic molecular targets that lack ketamine’s psychotomimetic side effects and abuse liability but retain its rapid onset of efficacy. However, many fundamental questions remain regarding the neurobiological mechanisms underlying ketamine’s rapid antidepressant effects and the puzzling persistence of benefits observed in some patients following a single dose. This book examines how insights from these studies are forging new conceptual models of the neurobiology of stress-related affective, anxiety, and addictive disorders and the nature of treatment resistance. It also discusses how ketamine’s rapid antidepressant effects provide a scientific platform to facilitate innovation in clinical trial designs pertaining to patient selection, choice of control group, outcome measures, and dose-optimization. This book brings together data and insights from this rapidly expanding and extraordinarily promising field of study. Readers will be able to extract integrated themes and useful insights from the material contained in these diverse chapters and appreciate the paradigm-shifting contributions of ketamine to modern psychiatry and clinical neuroscience research.

Ketamine for Depression

Ketamine for Depression Book
Author : Dr. Stephen J. Hyde
Publisher : Xlibris Corporation
Release : 2015-09-04
ISBN : 1503509532
Language : En, Es, Fr & De

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Book Description :

Given the unacceptably high rates of suffering, disability and premature death experienced by people with treatment-resistant depression and the surprisingly low rates of problems arising from the use of ketamine to treat the disorder, this is a therapy that all patients and their doctors should be discussing. This book summarises the research that has been carried out into ketamine for the treatment of depression over the past 15 years and, most importantly, describes different ways of using ketamine that are both practical and cost–effective. Currently most ketamine therapy is given intravenously in specialised clinics at considerable expense, but the author has successfully treated patients with low-dose sublingual ketamine and his patients have been able to safely take this at home. Profits from the sales of this book will assist further research into the use of ketamine for the treatment of depression.

11 THE USE OF SUBCUTANEOUS KETAMINE FOR TREATMENT RESISTANT DEPRESSION

11   THE USE OF SUBCUTANEOUS KETAMINE FOR TREATMENT RESISTANT DEPRESSION Book
Author : Mariane Quieroti Rodrigues
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Introduction: Major depressive disorder is highly common with up to 50% to 60% of the patients not achieving adequate response following antidepressant treatment. In this scenario, ketamine emerges as an important alternative to conventional treatments, with its action of being an antagonist of N-methyl- D-aspartate (NMDA) receptor, once its has a quick and effective action. Ketamine is most frequently administered intravenous. However, oral, sublingual, transmucosal, intranasal, subcutaneous (SC), and intramuscular routes of administration have also been examined.Aim: This study aims to investigate whether SC ketamine is effective in the treatment of unipolar major depression and if it has more effective and sustainable response than electroconvulsivetherapy (ECT).Methods: Participants will be comprised of patients with unipolar depression resistant to conventional treatment, men and women, aged u2265 18 across a range of ethnicities, recruited from General Hospital Servidor of State of Su00e3o Paulo, Brazil. Participants will be separeted in two groups. The first one will recieve a SC administration of ketamine in the dose of 0,5mg/kg weekly, for 6 weeks. The second will be submitted to ECT treatment, two sessions a week, for at least 8 sessions. The response of each treatment will be evaluated and compared by MADRS questionnaire.Results: We expect that SC ketamine has a good response in the treatment of major depression and that it has a similar response compared to ECT.Conclusion: SC ketamine, once it is a secure, quick and simple procedure, is a promising alternative to the available treatments.

Ketamine for Treatment Resistant Depression

Ketamine for Treatment Resistant Depression Book
Author : Gustavo H. Vazquez,Carlos A. Zarate,Elisa Brietzke
Publisher : Academic Press
Release : 2020-10-01
ISBN : 0128210346
Language : En, Es, Fr & De

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Book Description :

Ketamine for Treatment-Resistant Depression: Neurobiology and Applications provides a simple, evidence-based overview for neuropsychiatrists and translational researchers on this medication, its mechanisms of actions, eligibility of patients for treatment, and the preparation and implementation of ketamine clinics. Provides efficacy research on ketamine as a treatment for depression Identifies best practices for clinical use, both long-term and acute Discusses the molecular mechanisms and neurobiology of action

Ketamine for Treatment Resistant Depression

Ketamine for Treatment Resistant Depression Book
Author : Sanjay J. Mathew,Carlos A. Zarate, Jr.
Publisher : Adis
Release : 2018-07-07
ISBN : 9783319826950
Language : En, Es, Fr & De

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Book Description :

This book brings together an international group of clinicians and researchers from a broad swath of inter-related disciplines to offer the most up-to-date information about clinical and preclinical research into ketamine and second-generation “ketamine-like” fast-acting antidepressants. Currently available antidepressant medications act through monoaminergic systems, are ineffective for many individuals suffering from depression, and are associated with a delayed onset of peak efficacy of several months. The unexpected emergence of ketamine, an anesthetic N-methyl-D-aspartate (NMDA) receptor antagonist, as a rapid-acting antidepressant has reinvigorated CNS drug discovery research and catalyzed investigation in patient populations historically ignored in antidepressant drug development programs, particularly treatment-resistant patients and those with suicidality. Recent industry and academic research efforts have coalesced to explore NMDA receptor and glutamatergic molecular targets that lack ketamine’s psychotomimetic side effects and abuse liability but retain its rapid onset of efficacy. However, many fundamental questions remain regarding the neurobiological mechanisms underlying ketamine’s rapid antidepressant effects and the puzzling persistence of benefits observed in some patients following a single dose. This book examines how insights from these studies are forging new conceptual models of the neurobiology of stress-related affective, anxiety, and addictive disorders and the nature of treatment resistance. It also discusses how ketamine’s rapid antidepressant effects provide a scientific platform to facilitate innovation in clinical trial designs pertaining to patient selection, choice of control group, outcome measures, and dose-optimization. This book brings together data and insights from this rapidly expanding and extraordinarily promising field of study. Readers will be able to extract integrated themes and useful insights from the material contained in these diverse chapters and appreciate the paradigm-shifting contributions of ketamine to modern psychiatry and clinical neuroscience research.

Ketamine

Ketamine Book
Author : Kenji Hashimoto,Soichiro Ide,Kazutaka Ikeda
Publisher : Springer Nature
Release : 2020-03-05
ISBN : 9811529027
Language : En, Es, Fr & De

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Book Description :

This book presents the latest data from basic research and clinical trials supporting the effectiveness of ketamine as a treatment for depression, bipolar disorder, and suicidal behavior, setting these positive findings within the context of the serious problem of ketamine abuse. The first part of the book focuses on the evidence regarding ketamine abuse, with specific reference to Asian countries, and discusses countermeasures and complication management. It then addresses the mechanisms underlying the antidepressant and side effects of ketamine, which have remained elusive, describing and discussing important new research findings. Further, it explains insights gained from whole brain imaging in rodents and from behavioral pharmacology, and presents evidence regarding the role of gut microbiota, the NMDA receptor GluN2D subunit, and the lateral habenula in the actions of ketamine. These advances form the basis for the safer use of ketamine in patients with treatment-resistant depression and are expected to lead to the development of new antidepressants.

05 KETAMINE ANTIDEPRESSANT ACTIONS IN ELECTROCONVULSIVE THERAPY OF TREATMENT RESISTANT DEPRESSION

05   KETAMINE ANTIDEPRESSANT ACTIONS IN ELECTROCONVULSIVE THERAPY OF TREATMENT RESISTANT DEPRESSION Book
Author : Bruno Josu00e9 Prates
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Background and aims: Major depressive disorder affects approximately 5% of the population with nearly 1-third of patients failing to achieve remission, despite adequate pharmacological treatment [1]. Although electroconvulsive therapy (ECT) is the gold standard approach for treatment resistant depression (TRD), a considerable fraction of patients also show a delayed improvement or appear to be resistant to ECT. One of the most promising rapid-acting antidepressants is ketamine, a noncompetitive N-methyl-D-Aspartate receptor antagonist that can be used as an anesthetic during ECT to augment antidepressant efficacy [2].Data on ECTs using ketamine are both scarce and conflicting which lead the American Psychiatric Association to call for further studies [3]. We aim to clarify the potential synergism of ketamine and ECT for the treatment of TRD.Materials and methods: An experimental, non-randomized clinical trial with consecutive sampling of TRD patients with a HAM-D and PDAS scores u2265 23 was conducted. Patients that were initially assigned to 6 ECT sessions using thiopental anesthesia (ECT Std) but showed a very limited symptomatic relief were included in the study. Patients in Group 1 were then treated with further 6 ECT sessions using ketamine anesthesia (ECT Ket) whereas Group 2 maintained treatment with ECT Std (Fig. 1).Results: Clinical assessment showed no significant reduction in the mean HAM-D and PDAS scores for Group 1 but a significant reduction of the HAMD score of 38,8u00b12,4 to 13.4u00b110.55 (p

Ready Set Action Potential Breakthrough Therapy for Treatment Resistant Depression

Ready  Set  Action  Potential Breakthrough Therapy for Treatment Resistant Depression Book
Author : Alvin Garlejo
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Major depressive disorder is a psychiatric illness that is associated with a variety of debilitating symptoms such as persistent sadness, lack of interest and motivation, lassitude, pessimistic thoughts, and in severe cases, suicidal ideation and behavior. Current psychological and pharmacological treatments have been demonstrated efficacious; however, an ever-growing number of individuals frequently report minimal to no improvement with these treatments; and in some cases, a worsening of symptoms. This inadequacy to treatment is commonly known as treatment-resistant depression. At Kadima Neuropsychiatry Institute, Dr. Feifel treats individuals with treatment-resistant depression with advanced treatments such as TMS and ketamine. During my fieldwork internship at Kadima Neuropsychiatry Institute, my project focused on evaluating the efficacy of ketamine administered intramuscular to patients with treatment-resistant depression and determining which characteristics of a patient0́9s psychedelic experience or 0́−trip0́+ is associated with the decrease in their depressive symptoms. The results of this project demonstrated that an initial low dose of ketamine was significantly quick and efficacious in decreasing depressive symptoms in patients with treatment resistant depressive. In addition, a first of its kind exploratory analysis suggested that the intensity, positive content, and dissociative characteristics of a ketamine induced psychedelic trip were strongly associated with the decrease in depressive symptoms. Despite the significance in these results, more research needs to include a larger sample and explore the specific subjective characteristics within a psychedelic 0́−trip0́+ to further understand its association with a decrease in depressive symptoms. The quick and efficacious antidepressant effects of ketamine demonstrated in this project provide much potential for a program involving a mobile ketamine clinic to address severe depression and suicidality. Such therapeutic and intervention potentials can be explored further given an expansion of current policy limiting ketamine as a schedule III substance.

Ketamine for Treatment Resistant Depression

Ketamine for Treatment Resistant Depression Book
Author : Sanjay J. Mathew,Carlos A. Zarate, Jr.
Publisher : Springer
Release : 2016-11-25
ISBN : 3319429256
Language : En, Es, Fr & De

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Book Description :

This book brings together an international group of clinicians and researchers from a broad swath of inter-related disciplines to offer the most up-to-date information about clinical and preclinical research into ketamine and second-generation “ketamine-like” fast-acting antidepressants. Currently available antidepressant medications act through monoaminergic systems, are ineffective for many individuals suffering from depression, and are associated with a delayed onset of peak efficacy of several months. The unexpected emergence of ketamine, an anesthetic N-methyl-D-aspartate (NMDA) receptor antagonist, as a rapid-acting antidepressant has reinvigorated CNS drug discovery research and catalyzed investigation in patient populations historically ignored in antidepressant drug development programs, particularly treatment-resistant patients and those with suicidality. Recent industry and academic research efforts have coalesced to explore NMDA receptor and glutamatergic molecular targets that lack ketamine’s psychotomimetic side effects and abuse liability but retain its rapid onset of efficacy. However, many fundamental questions remain regarding the neurobiological mechanisms underlying ketamine’s rapid antidepressant effects and the puzzling persistence of benefits observed in some patients following a single dose. This book examines how insights from these studies are forging new conceptual models of the neurobiology of stress-related affective, anxiety, and addictive disorders and the nature of treatment resistance. It also discusses how ketamine’s rapid antidepressant effects provide a scientific platform to facilitate innovation in clinical trial designs pertaining to patient selection, choice of control group, outcome measures, and dose-optimization. This book brings together data and insights from this rapidly expanding and extraordinarily promising field of study. Readers will be able to extract integrated themes and useful insights from the material contained in these diverse chapters and appreciate the paradigm-shifting contributions of ketamine to modern psychiatry and clinical neuroscience research.

Intravenous Ketamine for Adults with Treatment Resistant Depression Or Post Traumatic Stress Disorder A Review of Clinical Effectiveness Cost Effectiveness and Guidelines

Intravenous Ketamine for Adults with Treatment Resistant Depression Or Post Traumatic Stress Disorder  A Review of Clinical Effectiveness  Cost Effectiveness and Guidelines Book
Author : Anonim
Publisher : Unknown
Release : 2019
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Intravenous Ketamine for Adults with Treatment Resistant Depression Or Post Traumatic Stress Disorder A Review of Clinical Effectiveness Cost Effectiveness and Guidelines book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Ketamine

Ketamine Book
Author : Kenji Hashimoto,Soichiro Ide,Kazutaka Ikeda
Publisher : Springer
Release : 2021-03-06
ISBN : 9789811529047
Language : En, Es, Fr & De

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Book Description :

This book presents the latest data from basic research and clinical trials supporting the effectiveness of ketamine as a treatment for depression, bipolar disorder, and suicidal behavior, setting these positive findings within the context of the serious problem of ketamine abuse. The first part of the book focuses on the evidence regarding ketamine abuse, with specific reference to Asian countries, and discusses countermeasures and complication management. It then addresses the mechanisms underlying the antidepressant and side effects of ketamine, which have remained elusive, describing and discussing important new research findings. Further, it explains insights gained from whole brain imaging in rodents and from behavioral pharmacology, and presents evidence regarding the role of gut microbiota, the NMDA receptor GluN2D subunit, and the lateral habenula in the actions of ketamine. These advances form the basis for the safer use of ketamine in patients with treatment-resistant depression and are expected to lead to the development of new antidepressants.

Ketamine

Ketamine Book
Author : Kenji Hashimoto,Soichiro Ide,Kazutaka Ikeda
Publisher : Springer
Release : 2020-04-28
ISBN : 9789811529016
Language : En, Es, Fr & De

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Book Description :

This book presents the latest data from basic research and clinical trials supporting the effectiveness of ketamine as a treatment for depression, bipolar disorder, and suicidal behavior, setting these positive findings within the context of the serious problem of ketamine abuse. The first part of the book focuses on the evidence regarding ketamine abuse, with specific reference to Asian countries, and discusses countermeasures and complication management. It then addresses the mechanisms underlying the antidepressant and side effects of ketamine, which have remained elusive, describing and discussing important new research findings. Further, it explains insights gained from whole brain imaging in rodents and from behavioral pharmacology, and presents evidence regarding the role of gut microbiota, the NMDA receptor GluN2D subunit, and the lateral habenula in the actions of ketamine. These advances form the basis for the safer use of ketamine in patients with treatment-resistant depression and are expected to lead to the development of new antidepressants.

Intravenous Ketamine for Treatment of Major Depressive Disorder in a Patient with a History of Repetitive Traumatic Brain Injuries

Intravenous Ketamine for Treatment of Major Depressive Disorder in a Patient with a History of Repetitive Traumatic Brain Injuries Book
Author : John William III
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

INTRODUCTION: Depression is the most common psychiatric disorder that occurs following a Traumatic Brain Injury. To date, there are limited studies demonstrating the effectiveness of current treatments for this disorder and even less for those with repetitive injuries or rTBIs. Ketamine has been demonstrated to be effective in successfully treating depression and helping with damaged connectivity within the brain. It can be hypothesized that Ketamine may help with both of these areas that many TBI patients face after injury. This particular case report describes the successful treatment of a patient with a history of rTBIs who struggled with depression for the past several years. CASE PRESENTATION: Mr. M is as 51 year old single caucasian male who presented to the Actify Neurotherapies Treatment Center for treatment of his Major Depressive Disorder. He had been depressed for five years but refused oral medication treatment due to fears over side effects. He presented with anergia, amotivation, feelings of sadness, anhedonia, impaired concentration and guilt/worthlessness with a QIDS score of 20 (Severe Depression) and GAD-7 of 18 (Severe Anxiety). Previous neuropsychological records revealed some cognitive impairment likely attributed to his multiple head injuries which included being hit over the head in an alley leading to amnesia for one month along with permanent anosmia. After completing a course of five Ketamine treatments, his symptoms either completely resolved or vastly improved as measured by the Levine Treatment Resistant Depression Scale (LRDTS). CONCLUSION: This case appears to be the first published report of a patient with multiple TBIs/rTBIs and Major depressive disorder successfully treated with intravenous ketamine. Overall, this illustrates the potential role that Ketamine may play in the treatment of psychiatric sequelae in individuals with a history of rTBIs. Ketamine has been demonstrated to increase BDNF and increase synaptogenesis which should encourage further research for brain injured individuals. Ketamine is also believed to potentially have neuroprotective effects as well which need to be further studied. Those with a history of one TBI are also at increased risk of having further rTBIs and therefore further increasing the chances of a depressive disorder. If one might be able to treat the individual before the repetitive event occurs, it may lead to quicker resolution of symptoms and may even decrease the chances of a subsequent event from occurring. Further studies are necessary to validate and replicate the symptom resolution of the above case but indicates that this treatment may be a potential viable rapid treatment option for those struggling without relief in sight.

EFFECTS OF KETAMINE ON EXPLICIT AND IMPLICIT SUICIDAL COGNITION A RANDOMIZED CONTROLLED TRIAL IN TREATMENT RESISTANT DEPRESSION

EFFECTS OF KETAMINE ON EXPLICIT AND IMPLICIT SUICIDAL COGNITION  A RANDOMIZED CONTROLLED TRIAL IN TREATMENT   RESISTANT DEPRESSION  Book
Author : Anonim
Publisher : Unknown
Release : 2014
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download EFFECTS OF KETAMINE ON EXPLICIT AND IMPLICIT SUICIDAL COGNITION A RANDOMIZED CONTROLLED TRIAL IN TREATMENT RESISTANT DEPRESSION book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Ketafusion LLC

Ketafusion  LLC Book
Author : Doris Tarrillion
Publisher : Unknown
Release : 2019
ISBN : 9781088322253
Language : En, Es, Fr & De

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Book Description :

Abstract: Depression is a debilitating and devastating mood disorder that can affect all ages and people of all races across all socioeconomic statuses. Conventional antidepressant medications only give one-third of relief from symptoms of depression, leaving the remainder to suffer from treatment-resistant depression (TRD). For the past two decades, researchers have looked into ketamine for the treatment of depression with promising results. All studies have validated that the intravenous (IV) use of ketamine is now the breakthrough treatment for TRD. This creates demand and a dire need to those are suffering from treatment-resistant depression. Ketafusion, LLC will specialize in delivery of safe and affordable intravenous ketamine infusion in the heart of Los Angeles County. It will provide personalized concierge care throughout every step of the treatment and recovery process to improve the quality of life of individuals battling TRD.

Ketamine

Ketamine Book
Author : Bita Moghaddam
Publisher : MIT Press Essential Knowledge
Release : 2021
ISBN : 0262542242
Language : En, Es, Fr & De

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Book Description :

"A complete and authoritative guide to the science of ketamine, the controversial yet current drug of choice for treating depression, a drug whose efficacy and impact is not yet well-established"--

Elucidation of Mechanisms that Determine the Responsiveness to Antidepressant Drug Treatments

Elucidation of Mechanisms that Determine the Responsiveness to Antidepressant Drug Treatments Book
Author : Mengyang Feng
Publisher : Unknown
Release : 2019
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Major depressive disorder (MDD) is a prevalent and debilitating psychiatric syndrome affecting approximately 4.4% of the worldwide. The therapeutic onset of currently available antidepressants is delayed by several weeks. About one third of MDD patients suffer from treatment resistant depression (TRD), meaning they do not respond to two or more different classes of conventional antidepressants. Although the rapid acting antidepressant ketamine exerts rapid and lasting antidepressant effects in more than half of TRD patients, ketamine still fails in some TRD patients, especially those associated with chronic inflammatory conditions. Increasing clinical evidence suggests that neuroinflammation is associated with increased vulnerability to MDD and poor response to antidepressants, however the neurophysiological changes that underlie treatment resistance remain to be elucidated. Recent preclinical studies suggest chronic exposure to high fat diet (HFD) in rodents induces a depressive-like brain state associated with heightened neuroinflammation and disrupted glucose homeostasis. Here we first confirmed that chronic HFD exposure of C57BL/6J mice results in abnormal glucose metabolism and neuroinflammation, as well as an anxious-depressive-like behavioral phenotype. We then assessed whether this HFD-induced depressive-like brain state is suitable to model treatment resistance. Indeed, we found that chronic HFD-induced anxious-depressive-like behavioral deficits are largely resistant to treatment with conventional antidepressants such as desipramine and fluoxetine, as well as to treatment with ketamine. Whole-cell patch clamp recordings of pyramidal cells in the prelimbic cortex (PLC) of HFD exposed mice revealed increased intrinsic excitability and increased hyperpolarization-activated cation currents (Ih currents). Based on these findings, we selected the voltage-gated K+ (Kv7 or KCNQ) channel opener retigabine and tested antidepressant effects of retigabine in a battery of behavioral tests. Subchronic retigabine treatment significantly ameliorated chronic HFD-induced anxious-depressive-like behaviors, andiiiiv these effects were associated with normalized neural excitability and Ih currents. Our data suggestthat increased intrinsic neural excitability may underlie the chronic HFD-induced treatment- resistant depressive-like brain state that can be normalized pharmacologically by agents that reduce neural excitability.Previous preclinical studies from our lab showed that heterozygous deletion of the 2 subunit (Gabrg2) of the -aminobutyric acid type A receptors (GABAARs) in mice (2+/- mice) results in modest defects in GABAergic neurotransmission and an anxious-depressive-like phenotype, whereas increasing synaptic inhibition of principle cells by genetically increasing the excitability of somatostatin (SST)-positive GABAergic interneurons (i.e. in SSTCre:2f/f mice) results in an antidepressant-like phenotype that mimics the effects of antidepressant drug treatment. Therefore, we hypothesized that a shift in the synaptic excitation to inhibition ratio (E:I ratio) towards increased excitation promotes anxiety and depression-related phenotypes while reducing this ratio result in an anxiolytic-antidepressant-like phenotype. Here we tested whether positive and negative shifts in E:I ratio of 2+/- and SSTCre: 2f/f would ameliorate or exacerbate the chronic HFD-induced depressive-like states. We found no significant differences in HFD- induced anxious-depressive-like behavioral deficits in 2+/- and SSTCre: 2f/f mice compared to WT mice with a battery of behavioral tests, suggesting that chronic HFD and synaptic E:I ratio changes mediate anxious-depressive-like states via distinct mechanisms.A recent study from our lab further demonstrated that functional defects in GABAergic synapses in 2+/- mice lead to homeostatic-like downregulation in surface level of N-Methyl-D- aspartic acid type glutamate receptors (NMDARs) and -amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid type glutamate receptors (AMPARs) that can be normalized with a single subanesthetic dose of ketamine. Given that the anxious-depressive-like behavioral deficits in 2+/- mice can be ameliorated with single subanesthetic dose of ketamine and chronic desipramine, wev speculated that the homeostatic upregulation of glutamatergic and GABAergic synapses alsocontributes to the antidepressant effects of conventional antidepressants. Preliminary results showed that chronic treatment of 2+/- mice with desipramine and fluoxetine leads to downregulation rather than upregulation of NMDARs, in contrast to ketamine. This indicates that conventional antidepressants and ketamine may exert antidepressants via different mechanisms.In summary, my dissertation established a chronic HFD-induced mouse model that is useful to study neuroinflammation-associated treatment-resistant depressive-like brain states. This brain state revealed increased intrinsic neural excitability and Ih currents as promising targets for development of future antidepressants. Moreover, the results showed that chronic HFD and changes in synaptic E:I ratio affect emotional states through distinct neural mechanisms. Lastly, preliminary results suggested that different antidepressant agents may exert antidepressant effects through different mechanism of neural plasticity.