Abstract:
:Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)-TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF-TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF-TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability.
journal_name
Transl Psychiatryjournal_title
Translational psychiatryauthors
Yang C,Shirayama Y,Zhang JC,Ren Q,Yao W,Ma M,Dong C,Hashimoto Kdoi
10.1038/tp.2015.136subject
Has Abstractpub_date
2015-09-01 00:00:00pages
e632issn
2158-3188pii
tp2015136journal_volume
5pub_type
杂志文章abstract::Brain-derived neurotrophic factor (BDNF) gene regulation has been linked to the pathophysiology of major depressive disorder (MDD). MDD patients show cognitive deficits, and altered BDNF regulation has a relevant role in neurocognitive functions. Our goal was to explore the association between BDNF genetic and epigene...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-019-0601-8
更新日期:2019-10-21 00:00:00
abstract::Although the diagnoses based on phenomenology have many practical advantages, accumulating evidence shows that schizophrenia and autism spectrum disorder (ASD) share some overlap in genetics and clinical presentation. It remains largely unknown how ASD-associated polygenetic risk contributes to the pathogenesis of sch...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-020-01001-2
更新日期:2020-09-21 00:00:00
abstract::The identification of convergent phenotypes in different models of psychiatric illness highlights robust phenotypes that are more likely to be implicated in disease pathophysiology. Here, we utilize human iPSCs harboring distinct mutations in DISC1 that have been found in families with major mental illness. One mutati...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-018-0281-9
更新日期:2018-11-08 00:00:00
abstract::Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality di...
journal_title:Translational psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1038/tp.2015.163
更新日期:2015-10-27 00:00:00
abstract::Cognitive impairments are pervasive and disabling features of schizophrenia. Targeted cognitive training (TCT) is a "bottom-up" cognitive remediation intervention with efficacy for neurocognitive outcomes in schizophrenia, yet individual responses are variable. Gamma oscillatory measures are leading candidate biomarke...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-020-01089-6
更新日期:2020-11-23 00:00:00
abstract::Current understanding and treatment of depression is limited to the monoaminergic theory with little knowledge of the involvement of other cellular processes. Genome-wide association studies, however, implicate several novel single-nucleotide polymorphisms with weak but replicable effects and unclarified mechanisms. W...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2016.221
更新日期:2016-11-08 00:00:00
abstract::The subthalamic nucleus (STN) has been shown to be implicated in the control of voluntary action, especially during tasks involving conflicting choice alternatives or rapid response suppression. However, the precise role of the STN during nonmotor functions remains controversial. First, we tested whether functionally ...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2014.73
更新日期:2014-09-09 00:00:00
abstract::Recent evidence has implicated the endocannabinoid (eCB) system in nicotine addiction. The eCB system also has an important role in reward mechanisms, and nicotine addiction has been associated with aberrant reward processing. Motivated by this evidence, we tested the hypothesis that eCB modulation of reward processin...
journal_title:Translational psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1038/tp.2013.6
更新日期:2013-02-26 00:00:00
abstract::CASK-related disorders are genetically defined neurodevelopmental syndromes. There is limited information about the effects of CASK mutations in human neurons. Therefore, we sought to delineate CASK-mutation consequences and neuronal effects using induced pluripotent stem cell-derived neurons from two mutation carrier...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-020-00994-0
更新日期:2020-09-14 00:00:00
abstract::Similar environmental risk factors have been implicated in different neuropsychiatric disorders (including major psychiatric and neurodegenerative diseases), indicating the existence of common epigenetic mechanisms underlying the pathogenesis shared by different illnesses. To investigate such commonality, we applied a...
journal_title:Translational psychiatry
pub_type: 杂志文章,meta分析
doi:10.1038/s41398-018-0358-5
更新日期:2019-01-22 00:00:00
abstract::This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1038/s41398-020-00987-z. ...
journal_title:Translational psychiatry
pub_type: 已发布勘误,撤回出版物
doi:10.1038/s41398-020-01116-6
更新日期:2020-12-01 00:00:00
abstract::Available data indicate that patients with depression and anxiety disorders are likely to be at greater risk for suicide. Therefore, it is important to correctly diagnose patients with depression and anxiety disorders. However, there are still no empirical laboratory methods to objectively diagnose these patients. In ...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-018-0245-0
更新日期:2018-09-19 00:00:00
abstract::Variants at microRNA-137 (MIR137), one of the most strongly associated schizophrenia risk loci identified to date, have been associated with poorer cognitive performance. As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2016.286
更新日期:2017-01-24 00:00:00
abstract::Early-life stress is a critical risk factor for developing psychopathological alterations later in life. This early adverse environment has been modeled in rats by exposure to stress during the peripubertal period-that is, corresponding to childhood and puberty-and has been shown to lead to increased emotionality, dec...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2014.54
更新日期:2014-07-08 00:00:00
abstract::Stress-induced disturbances of brain homeostasis and neuroinflammation have been implicated in the pathophysiology of mood disorders. In major depressive disorder (MDD), elevated levels of proinflammatory cytokines and chemokines can be found in peripheral blood, but very little is known about the changes that occur d...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-020-00992-2
更新日期:2020-09-11 00:00:00
abstract::Mitochondrial dysfunction might have a central role in the pathophysiology of depression. Phenotypically, depression is characterized by lack of energy, concentration problems and fatigue. These symptoms might be partially explained by reduced availability of adenosine triphosphate (ATP) as a consequence of impaired m...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2014.44
更新日期:2014-06-10 00:00:00
abstract::Protocadherin-19 (PCDH19) pathogenic variants cause an early-onset seizure disorder called girls clustering epilepsy (GCE). GCE is an X-chromosome disorder that affects heterozygous females and mosaic males, however hemizygous ("transmitting") males are spared. We aimed to define the neuropsychiatric profile associate...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-020-0803-0
更新日期:2020-05-04 00:00:00
abstract::Transcranial magnetic stimulation (TMS) is an approved intervention for treatment-resistant depression (TRD), but current targeting approaches are only partially successful. Our objectives were (1) to examine the feasibility of MRI-guided TMS in the clinical setting using a recently published surface-based, multimodal...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-020-00970-8
更新日期:2020-08-12 00:00:00
abstract::Panic disorder (PD) affects about four million Europeans, with women affected twice as likely as men, causing substantial suffering and high economic costs. The etiopathogenesis of PD remains largely unknown, but both genetic and environmental factors contribute to risk. An epigenome-wide association study (EWAS) was ...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-017-0026-1
更新日期:2017-12-18 00:00:00
abstract::Abnormally low γ-aminobutyric acid (GABA) levels have been consistently reported in adults with major depressive disorder (MDD). Our group extended this finding to adolescents, and documented that GABA deficits were associated with anhedonia. Here we aimed to confirm our prior finding of decreased brain GABA in youth ...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2017.187
更新日期:2017-08-22 00:00:00
abstract::Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-8...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2015.151
更新日期:2015-10-13 00:00:00
abstract::Recent advances in genome-wide DNA methylation (DNAm) profiling for smoking behaviour have given rise to a new, molecular biomarker of smoking exposure. It is unclear whether a smoking-associated DNAm (epigenetic) score has predictive value for ageing-related health outcomes which is independent of contributions from ...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-019-0576-5
更新日期:2019-10-07 00:00:00
abstract::Prenatal exposure to teratogenic substances, such as nicotine or alcohol, increases the risk of developing attention-deficit/hyperactivity disorder (ADHD). To date, studies examining this relationship have used symptom scales as outcome measures to assess the effect of prenatal exposure, and have not investigated the ...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2012.12
更新日期:2012-03-06 00:00:00
abstract::Depression is one of the most prevalent and debilitating psychiatric disorders worldwide. Recently, we showed that both relatively short and relatively long cytosine-adenine-guanine (CAG) repeats in the huntingtin gene (HTT) are associated with an increased risk of lifetime depression. However, to what extent the vari...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2017.116
更新日期:2017-06-06 00:00:00
abstract::Engaging in physical activity is known to reduce depressive symptoms. However, little is known which behavioral factors are relevant, and how patterns of activity change during depressive episodes. We expected that compared to controls, in depressed individuals the level of activity would be lower, the amplitude of 24...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-020-00952-w
更新日期:2020-07-30 00:00:00
abstract::Myelination and neurite outgrowth both occur during brain development, and their disturbance has been previously been implicated in the pathophysiology of schizophrenia. Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is a potent negative regulator of axonal myelination and neurite extension...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2013.121
更新日期:2014-01-21 00:00:00
abstract::Although maltreatment experiences in childhood increase the risk for depression, not all maltreated children become depressed. This review aims to systematically examine the existing literature to identify modifiable factors that increase vulnerability to, or act as a buffer against, depression, and could therefore in...
journal_title:Translational psychiatry
pub_type: 杂志文章,meta分析,评审
doi:10.1038/tp.2017.140
更新日期:2017-07-04 00:00:00
abstract::The catechol-o-methyltransferase (COMT) genetic variations produce pleiotropic behavioral/neuroanatomical effects. Some of these effects may vary among sexes. However, the developmental trajectories of COMT-by-sex interactions are unclear. Here we found that extreme COMT reduction, in both humans (22q11.2 deletion syn...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/tp.2017.109
更新日期:2017-05-30 00:00:00
abstract::The neural correlates distinguishing youth with Autism Spectrum Disorder (ASD-) and ASD with co-occurring Attention Deficit Hyperactivity Disorder (ASD+) are poorly understood despite significant phenotypic and prognostic differences. Paired-pulse transcranial magnetic stimulation (TMS) measures, including intracortic...
journal_title:Translational psychiatry
pub_type: 杂志文章
doi:10.1038/s41398-019-0614-3
更新日期:2019-11-13 00:00:00
abstract::Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear. Knowledge gained on the biological basis of Pavlovian conditioning has led to the general acceptance that fear extinction may be a useful model in understand...
journal_title:Translational psychiatry
pub_type: 杂志文章,评审
doi:10.1038/tp.2014.67
更新日期:2014-08-05 00:00:00