scholarly journals Shifting hippocampal excitation/inhibition balance modifies despair-like behavior in mice

2020 ◽  
Author(s):  
Sang Ho Yoon ◽  
Geehoon Chung ◽  
Woo Seok Song ◽  
Sung Pyo Oh ◽  
Sang Jeong Kim ◽  
...  
Keyword(s):  
Depressive Disorders ◽  
Neural Circuits ◽  
Behavioral Effects ◽  
Gabaergic Transmission ◽  
Ca1 Neurons ◽  
Trkb Receptor ◽  
Core Symptom ◽  
Synaptic Modification ◽  
Antidepressant Effects ◽  
Interneuron Activity

AbstractDespair is a core symptom of depressive disorders. However, little is known about the neural circuits mediating despair and how they are modified by antidepressants. Here we show that the balance between excitatory and inhibitory neurotransmission (E/I balance) in the hippocampus affects behavioral despair in mice. Reduced interneuron density, knockdown of Gabrg2 or DREADD-mediated suppression of interneuron activity resulted in disinhibition of CA1 neurons and anti-despair-like behaviors in mice. Conversely, pharmacological and chemogenetic potentiation of GABAergic transmission in CA1 neurons rapidly induced despair-like behaviors. Disinhibition induced by the GABAAR antagonist pentylenetetrazol produced transient antidepressant effects without BDNF elevation in the hippocampus, while ketamine exhibited rapid and sustained antidepressant effects, but the latter was sensitive to the TrkB receptor blocker ANA-12. These results suggest that rapid disinhibition and BDNF-induced long-lasting synaptic modification leads to enhanced E/I balance, which may contribute to acute and sustained behavioral effects of rapid-acting antidepressants.

New Drug Discovery from Medicinal Plants and Phytoconstituents for Depressive Disorders

2019 ◽  
Vol 18 (2) ◽  
pp. 92-102 ◽  
Author(s):  
Fatma Tuğçe Gürağaç Dereli ◽  
Mert Ilhan ◽  
Esra Küpeli Akkol
Keyword(s):  
Medicinal Plants ◽  
Depressive Disorders ◽  
Living Standards ◽  
Side Effect Profile ◽  
Active Components ◽  
Synthetic Drugs ◽  
Traditional Medicinal Plants ◽  
Antidepressant Effects ◽  
Life Threatening ◽  
Culinary Herbs

Background & Objective: Depression, a risk factor for several serious diseases, is a highly prevalent and life-threatening psychiatric disorder. It can affect the individual’s position in life and reduce the living standards. The research on the use of medicinal plants in treating this disease has increased enormously because of the possible low rehabilitation rate and side effects of available synthetic drugs, such as sexual dysfunction, nausea, fatigue, insomnia, hypersomnia, and weight gain.Conclusion:Therefore, this review aimed to draw attention to the antidepressant effects of culinary herbs and traditional medicinal plants and their active components, thereby promoting their use in the development of more potent antidepressants with improved side effect profile.

The Onset and Rate of the Antidepressant Effect of Electroconvulsive Therapy

1993 ◽  
Vol 162 (6) ◽  
pp. 725-732 ◽  
Author(s):  
Allan I. F. Scott ◽  
Lawrence J. Whalley
Keyword(s):  
Electroconvulsive Therapy ◽  
Royal College ◽  
Mode Of Action ◽  
Depressive Disorders ◽  
Practical Interest ◽  
Antidepressant Effect ◽  
Rapid Improvement ◽  
Research Committee ◽  
Biological Studies ◽  
Antidepressant Effects

This annotation is concerned with how soon and at what rate antidepressant effects become apparent over a course of electroconvulsive therapy (ECT). The first question is of importance in the design and interpretation of biological studies of the mode of action of ECT. The second question is of practical interest to the treating psychiatrist when we ask how the speed of recovery is influenced by what the psychiatrist prescribes, that is, the number and frequency of treatments. These questions are little better answered now than 20 years ago. This may come as a surprise to many readers, who have been advised to use ECT when “seeking rapid improvement” in depressive disorders (ECT Sub-Committee of the Research Committee of the Royal College of Psychiatrists, 1989). This lack of progress is attributable to a dearth of appropriately designed ECT studies.

scholarly journals The Role of Brain-Derived Neurotrophic Factor in Mediating the Action of Antidepressants in the Treatment of Depression

2019 ◽  
Vol 74 (1) ◽  
pp. 20-28 ◽  
Author(s):  
Tamara I. Vazagaeva ◽  
Roman V. Akhapkin ◽  
Yuri A. Alexandrovsky
Keyword(s):  
Neurotrophic Factor ◽  
Depressive Disorders ◽  
Therapeutic Response ◽  
Molecular Genetic ◽  
Genetic Studies ◽  
Trkb Receptor ◽  
Treatment Of Depression ◽  
Antidepressant Efficacy ◽  
Chronic Course

According to the neurotrophic hypothesis of depression proposed two decades ago, the most important role in the pathogenesis of depressive disorders is played by abnormalities in the maintenance of neuronal plasticity regulated by brain neurotrophic factor (BDNF). Although the decline in BDNF activity in depression is now widely documented, it remains unclear whether it is a factor contributing to the onset of depression, or a consequence of the chronic course of the disease. In preclinical studies, it was found that exogenous BDNF infusions causes antidepressant-like effects, prevents the depressogenic effects of chronic stress and increases cell survival in the hippocampus and the prefrontal cortex, but the mechanisms mediating these effects have not been fully studied. The results of molecular genetic studies confirmed that BDNF is essential in mediating the therapeutic effect of antidepressants, while the role of genetic polymorphisms in predicting antidepressant efficacy in depression remains uncertain. The mechanisms of action of monoaminergic antidepressants are related to their effect on the expression of BDNF and its TrkB receptor, however, apparently, the effect size varies for different drugs. Peripheral BDNF levels increase during treatment with antidepressants, and this increase is clearly observed only during the acute phase treatment of depression, but not during the period of maintenance therapy. The serum level of BDNF is a potentially useful marker for diagnosing depression and prediction of a therapeutic response.

scholarly journals Future Directions for Clinical Psychedelic Research: The Relaxed Symptom Network

2021 ◽  
Author(s):  
Evan Lewis-Healey ◽  
Ruben Laukkonen ◽  
Michiel van Elk
Keyword(s):  
Clinical Trials ◽  
Mental Disorders ◽  
Network Theory ◽  
Depressive Disorders ◽  
Clinical Work ◽  
Future Directions ◽  
Specific Symptom ◽  
Antidepressant Effects ◽  
Clinical Action ◽  
Broad Overview

Recent clinical trials have demonstrated that psilocybin may have strong antidepressant effects, and may be effective in the treatment of depressive disorders when embedded in a psychotherapeutic protocol (psychedelic-assisted psychotherapy; PAP). There are now dozens of registered and ongoing clinical trials that intend to test for the efficacy of psilocybin within a psychotherapeutic protocol. Despite promising results, the mechanism(s) that may be responsible for the antidepressant effects of PAP are still hotly contested. In this paper, we provide a broad overview of the recent clinical work conducted with psychedelics on depressive disorders, and summarise several theories of action of PAP. Extending on the state of the field, we argue that the ‘Network Theory of Mental Disorders’ is a useful tool for clinical research with psychedelics. We hypothesise that, if PAP is successful, the connections between symptoms in a network will weaken, thereby rendering the patient less vulnerable to developing or relapsing into depression. We argue that application of the Network Theory may (a) provide deeper insights into the effects of PAP on specific symptom interactions, both on an interindividual and intraindividual basis, (b) generate fruitful hypotheses for the clinical action of PAP, and (c) provide a pre-emptive tool for making the most of ‘intentions’ preceding and during psychedelic experiences. These findings we hope will ultimately improve responsiveness and reduce relapse in response to this promising therapy.

scholarly journals Role of Serotonergic System in the Antidepressant Actions of mGlu2/3 Receptor Antagonists: Similarity to Ketamine

2019 ◽  
Vol 20 (6) ◽  
pp. 1270 ◽  
Author(s):  
Shigeyuki Chaki ◽  
Kenichi Fukumoto
Keyword(s):  
Depressive Disorders ◽  
Serotonergic System ◽  
Rodent Models ◽  
Receptor Antagonists ◽  
Metabotropic Glutamate ◽  
Antidepressant Effects ◽  
Major Depressive Disorders ◽  
Resistant Depression ◽  
Synaptic Mechanisms

Numerous studies have demonstrated the antidepressant effects of group II metabotropic glutamate (mGlu2/3) receptor antagonists in various rodent models. Importantly, it has been shown that the antidepressant effects of mGlu2/3 receptor antagonists in rodent models are similar to those of ketamine, which exerts rapid and long-lasting antidepressant effects in patients with major depressive disorders, including patients with treatment-resistant depression. In addition, the synaptic mechanisms underlying the effects of mGlu2/3 receptor antagonists are reported to be similar to those underlying the effects of ketamine. The roles of the serotonergic system in the antidepressant effects of mGlu2/3 receptor antagonists have recently been demonstrated. Moreover, it was investigated how mGlu2/3 receptor antagonists interact with the serotonergic system to exert antidepressant effects. Notably, the same neural mechanisms as those underlying the effects of ketamine may be involved in the antidepressant actions of the mGlu2/3 receptor antagonists. In this review, we shall summarize the antidepressant potential of mGlu2/3 receptor antagonists and their mechanisms of action in comparison with those of ketamine. In particular, we shall focus on the roles of the serotonergic system in the antidepressant actions of mGlu2/3 receptor antagonists.

Core Symptom Index (CSI): testing for bifactor model and differential item functioning

2019 ◽  
Vol 31 (12) ◽  
pp. 1769-1779
Author(s):  
Nahathai Wongpakaran ◽  
Tinakon Wongpakaran ◽  
Surang Lertkachatarn ◽  
Thanitha Sirirak ◽  
Pimolpun Kuntawong
Keyword(s):  
Differential Item Functioning ◽  
Depressive Disorders ◽  
Bifactor Model ◽  
Ordinal Scale ◽  
Common Variance ◽  
Symptom Index ◽  
Core Symptom ◽  
Item Functioning ◽  
Specific Factors ◽  
Explained Common Variance

ABSTRACTObjectives:The Core Symptom Index (CSI) is designed to measure anxiety, depression and somatization symptoms. This study examined the construct validity of CSI using confirmatory factor analysis (CFA) including a bifactor model and explored differential item functioning (DIF) of the CSI. The criterion and concurrent validity were evaluated.Methods:In all, 803 elderly patients, average age 69.24 years, 70% female, were assessed for depressive disorders and completed the CSI and the geriatric depression scale (GDS). A series involving CFA for ordinal scale was applied. Factor loadings and explained common variance were analyzed for general and specific factors; and Omega was calculated for model-based reliability. DIF was analyzed using the Multiple-Indicator Multiple-Cause model. Pearson’s correlation, ANOVA, and ROC analysis were used for associations and to compare CSI and GDS in predicting major depressive disorders (MDD).Results:The bifactor model provided the best fit to the data. Most items loaded on general rather than specific factors. The explained common variance was acceptable, while Omega hierarchical for the subscale and explained common variance for the subscales were low. Two DIF items were identified; ‘crying’ for sex items and ‘self-blaming’ for education items. Correlation among CSI and clinical disorders and the GDS were found. AUC for the GDS was 0.83, and for the CSI was 0.81.Conclusion:CSI appears sufficiently unidimensional. Its total score reflected a single general factor, permitting users to interpret the total score as a sufficient reliable measure of the general factors. CSI could serve as a screening tool for MDD.

scholarly journals Simultaneous optogenetic manipulation and calcium imaging in freely movingC. elegans

2013 ◽  
Author(s):  
Frederick B. Shipley ◽  
Christopher M. Clark ◽  
Mark J. Alkema ◽  
Andrew M. Leifer
Keyword(s):  
Neural Activity ◽  
Calcium Imaging ◽  
Neural Circuits ◽  
Neural Response ◽  
Sensory Stimuli ◽  
Systems Neuroscience ◽  
C Elegans ◽  
Fundamental Goal ◽  
Freely Moving ◽  
Interneuron Activity

A fundamental goal of systems neuroscience is to probe the dynamics of neural activity that drive behavior. Here we present an instrument to simultaneously manipulate neural activity via Channelrhodopsin, monitor neural response via GCaMP3, and observes behavior in freely moving C. elegans. We use the instrument to directly observe the relation between sensory stimuli, interneuron activity and locomotion in the mechanosensory circuit. Now published as: Front Neural Circuits 8:28, doi:10.3389/fncir.2014.00028

Treatment of Psychiatric Diseases with General Anaesthetics

2019 ◽  
pp. 315-322
Author(s):  
Laszlo Vutskits
Keyword(s):  
Clinical Trials ◽  
Major Depressive Disorder ◽  
Mental Disorders ◽  
Depressive Disorder ◽  
Depressive Disorders ◽  
Psychiatric Diseases ◽  
Therapeutic Role ◽  
Ordinary Life ◽  
Behavioural Patterns ◽  
Antidepressant Effects

Psychiatric disorders are defined as mental or behavioural patterns causing either suffering or a poor ability to function in ordinary life. These conditions are generally characterized by a combination of abnormal thoughts, perceptions, emotions, behaviour, and relationships with others. The burden of mental disorders continues to grow and the estimated global lifetime prevalence of these pathological states is estimated to reach over one-third of the population worldwide. Depression, one of the most common psychiatric diseases, is difficult to treat. This chapter on the treatment of psychiatric diseases with general anaesthetics includes discussion of major depressive disorder and its epidemiology and treatments, clinical trials suggesting a therapeutic role for anaesthesia in patients with depressive disorders, rapid antidepressant effects of ketamine, and mechanisms of actions underlying the antidepressant effects of anaesthetics.

Research Domain Criteria (RDoC): A Perspective to Probe the Biological Background behind Treatment Efficacy in Depression

2021 ◽  
Vol 28 ◽  
Author(s):  
Marco Calabrò ◽  
Chiara Fabbri ◽  
Siegfried Kasper ◽  
Joseph Zohar ◽  
Daniel Souery ◽  
...  
Keyword(s):  
Depressive Disorders ◽  
Health Concern ◽  
Research Domain Criteria ◽  
Major Depressive ◽  
Major Health ◽  
Antidepressant Effects ◽  
Research Domain ◽  
Drugbank Database ◽  
Antidepressant Action

Background: Major Depressive Disorder (MDD) and its frequent partial response to antidepressants are a major health concern and therefore an important focus of research. Despite the efforts, MDD pathogenesis and the mechanisms of antidepressant action are only partially understood. In the last few years, the need of rethinking the classification of depressive disorders and psychiatric disorders in general has been suggested, in order to provide a nosology that reflects more closely the biological background associated with disease pathogenesis and its role/significance in treatment. The classification proposed by the National Institute of Mental Health (NIMH), namely the research domain criteria (RDoC), may represent a key framework to guide research in this direction. Methods: A literature search was performed on PubMed and Google Scholar databases in order to retrieve data regarding Antidepressants effects on specific RDoC constructs. Further, the targets of drugs of interest were identified through Drugbank database, and their possible function within RDoC constructs was discussed. Discussion: In this review we summarize and discuss the significance of the results of pre-clinical and clinical studies investigating specific RDoC paradigms relevant to depressive phenotypes and antidepressant effects.

scholarly journals Neural Plasticity and Proliferation in the Generation of Antidepressant Effects: Hippocampal Implication

2013 ◽  
Vol 2013 ◽  
pp. 1-21 ◽  
Author(s):  
Fuencisla Pilar-Cuéllar ◽  
Rebeca Vidal ◽  
Alvaro Díaz ◽  
Elena Castro ◽  
Severiano dos Anjos ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Depressive Disorders ◽  
Intracellular Signalling ◽  
Trophic Factors ◽  
Signalling Pathways ◽  
Vascular Endothelial ◽  
Functional Changes ◽  
Intracellular Signalling Pathways ◽  
Antidepressant Effects ◽  
Endothelial Growth Factor

It is widely accepted that changes underlying depression and antidepressant-like effects involve not only alterations in the levels of neurotransmitters as monoamines and their receptors in the brain, but also structural and functional changes far beyond. During the last two decades, emerging theories are providing new explanations about the neurobiology of depression and the mechanism of action of antidepressant strategies based on cellular changes at the CNS level. The neurotrophic/plasticity hypothesis of depression, proposed more than a decade ago, is now supported by multiple basic and clinical studies focused on the role of intracellular-signalling cascades that govern neural proliferation and plasticity. Herein, we review the state-of-the-art of the changes in these signalling pathways which appear to underlie both depressive disorders and antidepressant actions. We will especially focus on the hippocampal cellularity and plasticity modulation by serotonin, trophic factors as brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) through intracellular signalling pathways—cAMP, Wnt/β-catenin, and mTOR. Connecting the classic monoaminergic hypothesis with proliferation/neuroplasticity-related evidence is an appealing and comprehensive attempt for improving our knowledge about the neurobiological events leading to depression and associated to antidepressant therapies.

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