Chronic Stress最新文献

{"title":"The Predictive Value of Early-Life Trauma, Psychopathy, and the Testosterone-Cortisol Ratio for Impulsive Aggression Problems in Veterans.","authors":"Pauline O J Korpel,&nbsp;Tim Varkevisser,&nbsp;Sylco S Hoppenbrouwers,&nbsp;Jack Van Honk,&nbsp;Elbert Geuze","doi":"10.1177/2470547019871901","DOIUrl":"https://doi.org/10.1177/2470547019871901","url":null,"abstract":"<p><strong>Background: </strong>In this study, we examined whether early-life trauma, psychopathy, and the testosterone/cortisol ratio predicted impulsive aggression problems in veterans.</p><p><strong>Method: </strong>A sample of 49 male veterans with impulsive aggression problems and 51 nonaggressive veterans were included in the study. Logistic regression analysis was performed with early-life trauma, primary and secondary psychopathy, and testosterone/cortisol ratio as continuous predictor variables; impulsive aggression status was entered as a binary outcome measure. Correlation analyses were conducted to examine pairwise relations among the predictors.</p><p><strong>Results: </strong>Results indicated that early-life trauma and secondary psychopathy, but not the testosterone/cortisol ratio or primary psychopathy, were significant predictors of impulsive aggression status.</p><p><strong>Conclusions: </strong>The current results indicate that early-life trauma and secondary psychopathy are risk factors for impulsive aggression problems among veterans. Future studies are needed to determine the exact causal relations among the variables examined here.</p>","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":" ","pages":"2470547019871901"},"PeriodicalIF":0.0,"publicationDate":"2019-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2470547019871901","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37962135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to Chronic Unpredictable Stress Reduces Immunostaining for Connexins 43 and 30 and Myelin Basic Protein in the Rat Prelimbic and Orbitofrontal Cortices.","authors":"","doi":"10.1177/2470547019869755","DOIUrl":"https://doi.org/10.1177/2470547019869755","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/2470547018814186.].</p>","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":" ","pages":"2470547019869755"},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2470547019869755","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37962129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-6 Signaling in Monocytes: A Potential Therapeutic Avenue for Stress-Induced Mood Impairments","authors":"A. Niraula, J. Sheridan","doi":"10.1177/2470547019871371","DOIUrl":"https://doi.org/10.1177/2470547019871371","url":null,"abstract":"Approximately 30% of patients with mood disorders fail to respond to available therapies, which are primarily geared toward modulating the catecholaminergic system. Recent developments in psychoneuroimmunology have unraveled a key role for inflammatory mediators in the development and maintenance of mood disorders. Indeed, mounting evidence on the brain– body bidirectional communication in health and disease has highlighted the need for a fundamental shift in the current approach toward treatment. Interleukin (IL-6) is a cytokine strongly and consistently associated with depression and anxiety in humans. Plasma IL-6 levels are found to be significantly higher in depressed patients nonresponsive to SSRI treatments. Furthermore, recent reports suggest that high prevalence of inflammatory cytokines, including IL-6, may account for treatment failure in depression. In another example depicting inflammatory modulation of affective symptoms, antiCRP (C-reactive protein) antibodies improved outcomes in depressed patients nonresponsive to antidepressants and with high plasma CRP levels. Overall, these findings of high cytokine and acute phase protein levels concurrent with treatment-resistant symptoms warrant a thorough investigation into the relationship between inflammatory signaling and neuronal functions in mood disorders. We investigated the relationship between IL-6 and behavioral impairments in a preclinical rodent model of psychosocial stress. Repeated social defeat (RSD) stress triggers the release of bone marrow-derived monocytes, which following recruitment to the brain vasculature, trigger an inflammatory response in the brain parenchyma via IL-1 receptor signaling on the reactive endothelium. This monocyte IL-1 signaling at the neurovascular interface during RSD is critical to the development of anxiety-like behavior. Strikingly, we found that IL-6-deficient (IL-6 / ) mice exposed to RSD were protected from anxiety-like and social avoidance behavior, despite monocyte accumulation in the brain vasculature. Transcriptional profiling of peripheral monocytes that trafficked to the brain revealed a stress-induced increase in pattern recognition (Cd14, TLR4, Myd88) genes, Mmp9, IL-1 and Stat3 expression, an effect diminished in the IL-6 / brain monocytes. This lack of the inflammatory signaling repertoire in recruited monocytes in IL-6 / mice may account for the resistance to anxiety-like behavior following RSD. Notably, our findings, the first to characterize a murine monocyte phenotype in the context of stress, are in line with clinical reports of peripheral inflammatory changes in chronic stress. Chronic stress in humans is associated with an increased prevalence of circulating CD14þCD16 monocytes, which elicit an exaggerated immune response to LPS treatment. This exaggerated inflammatory response in monocytes, which are also resistant to the immunosuppressive actions of glucocorticoids, is characteristic of a ‘‘primed’’ profile. We found that I","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2470547019871371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43030470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurophysiological Effect of Ketamine on Prefrontal Cortex in Treatment-Resistant Depression: A Combined Transcranial Magnetic Stimulation-Electroencephalography Study.","authors":"Nithya Ramakrishnan,&nbsp;Nicholas R E Murphy,&nbsp;Christopher P Walker,&nbsp;Valeria A Cuellar Leal,&nbsp;Jair C Soares,&nbsp;Raymond Y J Cho,&nbsp;Sudhakar Selvaraj","doi":"10.1177/2470547019861417","DOIUrl":"https://doi.org/10.1177/2470547019861417","url":null,"abstract":"Treatment-resistant depression (TRD) represents a substantial clinical and economic burden. A single subanesthetic dose of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine improves TRD depression symptoms within hours. The rapid response points to a fundamentally different mechanism which, while well modeled in preclinical studies, has yet to be translated into clinically relevant biomarkers. Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) are a direct index of the neurophysiological state of the stimulated cortical and cortico-thalamic network. TEPs have also previously shown a relationship with glutamatergic and Y-amino butyric acid (GABA)ergic neurotransmission suggesting that concurrent TMS–electroencephalography (EEG) can also be an index of local cortical excitability/inhibition balance. Animal studies suggest that ketamine not only increases glutamatergic excitatory drive in the prefrontal cortex (PFC) and limbic regions of the brain but also demonstrates GABAAR agonism. 3 This study aimed to observe changes in PFC cortical excitability measures indexed by a pharmaco-TMS–EEG approach by evaluating alterations in its component structure up to 24 hours postketamine infusion. Four TRD patients (mean age: 38.3 10.6 years; N 1⁄4 three females) provided written informed consent to participate. They received open-label intravenous infusion of 0.5mg/kg ketamine over 40 minutes. Patient’s depression levels were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D) at pre-ketamine baseline, and 4 hours and 24 hours post-ketamine infusion. Concurrent TMS stimulation and EEG recording were performed at all sessions. Biphasic single-pulse TMS (MagVenture MagPro) was presented at the left dorsolateral prefrontal cortex (DLPFC), for N1⁄4 200 pulses. The cortical response to TMS was recorded using 64-channel EEG (BrainAmp DC, BrainProducts), sampled at 5000Hz, with electrode wires reoriented to avoid direct contact with the TMS coil. Stimulation intensity was 120% of baseline resting motor threshold. EEG data were analyzed by replacing the TMS pulse period (0–20ms) with linear interpolation. Artifacts were removed using a two-tiered independent components analysis routine (ARTIST). This algorithm automatically identifies artifactual components based on features capturing the spatiotemporal profile of both neural and artifactual activities. Additional noise suppression employed the source-estimate-utilizing noisediscarding algorithm (SOUND). We utilized the local mean field amplitude–area under the curve (LMFA– AUC) from a subset of electrodes (Figure 1(d)) around the stimulation site as our primary outcome measure. This has previously been reported as a reliable index of cortical reactivity or excitation. We applied the SOUND correction to individual trials to test within-subject differences from session to session using nonparametric Kruskal–Wallis","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":" ","pages":"2470547019861417"},"PeriodicalIF":0.0,"publicationDate":"2019-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2470547019861417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37962133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocannabinoid System Alterations in Posttraumatic Stress Disorder: A Review of Developmental and Accumulative Effects of Trauma","authors":"Anahita Bassir Nia, Ricci Bender, I. Harpaz-Rotem","doi":"10.1177/2470547019864096","DOIUrl":"https://doi.org/10.1177/2470547019864096","url":null,"abstract":"The role of the endocannabinoid system in stress-related psychiatric symptoms has been investigated in many animal and human studies. Although most of these studies consistently report long-lasting effects of prolonged stress and trauma on the endocannabinoid system, the nature and direction of these changes are controversial. We reviewed the available preclinical and clinical studies investigating the endocannabinoid system alterations long after chronic stress and trauma. We propose that the effects of prolonged stress or trauma on the endocannabinoid system are different based on the developmental age of subjects at the time of experiencing the trauma and its repetitiveness and accumulative effects. The current literature consistently demonstrates decreased levels of endocannabinoid ligands and receptors if the trauma occurs in childhood, whereas decreased levels of endocannabinoid ligands and increased levels of cannabinoid receptors are reported when trauma has happened in adulthood. It is important to note that these changes are region-specific in the brain and also there are important sex differences, which are beyond the scope of this review.","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2470547019864096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49015591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Targets for Fast Antidepressant Responses: Possible Role of Endogenous Neuromodulators.","authors":"Anderson Camargo, Ana Lúcia S Rodrigues","doi":"10.1177/2470547019858083","DOIUrl":"10.1177/2470547019858083","url":null,"abstract":"<p><p>The available medications for the treatment of major depressive disorder have limitations, particularly their limited efficacy, delayed therapeutic effects, and the side effects associated with treatment. These issues highlight the need for better therapeutic agents that provide more efficacious and faster effects for the management of this disorder. Ketamine, an N-methyl-D-aspartate receptor antagonist, is the prototype for novel glutamate-based antidepressants that has been shown to cause a rapid and sustained antidepressant effect even in severe refractory depressive patients. Considering the importance of these findings, several studies have been conducted to elucidate the molecular targets for ketamine's effect. In addition, efforts are under way to characterize ketamine-like drugs. This review focuses particularly on evidence that endogenous glutamatergic neuromodulators may be able to modulate mood and to elicit fast antidepressant responses. Among these molecules, agmatine and creatine stand out as those with more published evidence of similarities with ketamine, but guanosine and ascorbic acid have also provided promising results. The possibility that these neuromodulators and ketamine have common neurobiological mechanisms, mainly the ability to activate mechanistic target of rapamycin and brain-derived neurotrophic factor signaling, and synthesis of synaptic proteins in the prefrontal cortex and/or hippocampus is presented and discussed.</p>","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":" ","pages":"2470547019858083"},"PeriodicalIF":0.0,"publicationDate":"2019-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b4/9b/10.1177_2470547019858083.PMC7219953.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37962131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontal Lobe Circuitry in Posttraumatic Stress Disorder.","authors":"Lynn D Selemon, Keith A Young, Dianne A Cruz, Douglas E Williamson","doi":"10.1177/2470547019850166","DOIUrl":"10.1177/2470547019850166","url":null,"abstract":"<p><p>Symptoms of posttraumatic stress disorder include hyperarousal, avoidance of trauma-related stimuli, re-experiencing of trauma, and mood changes. This review focuses on the frontal cortical areas that form crucial links in circuitry pertinent to posttraumatic stress disorder symptomatology: (1) the conditioned fear extinction circuit, (2) the salience circuit, and (3) the mood circuit. These frontal areas include the ventromedial prefrontal cortex (conditioned fear extinction), the dorsal anterior cingulate and insular cortices (salience), and the lateral orbitofrontal and subgenual cingulate cortices (mood). Frontal lobe structural abnormalities in posttraumatic stress disorder, including volumetric reductions in the cingulate cortices, impact all three circuits. Functional analyses of frontal cortices in posttraumatic stress disorder show abnormal activation in all three according to task demand and emotional valence. Network analyses reveal altered amygdalo-frontal connectivity and failure to suppress the default mode network during cognitive engagement. Spine shape alterations also have been detected in the medial orbito-frontal cortex in posttraumatic stress disorder postmortem brains, suggesting reduced synaptic plasticity. Importantly, frontal lobe abnormalities in posttraumatic stress disorder extend beyond emotion-related circuits to include the lateral prefrontal cortices that mediate executive functions. In conclusion, widespread frontal lobe dysfunction in posttraumatic stress disorder provides a neurobiologic basis for the core symptomatology of the disorder, as well as for executive function impairment.</p>","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49570472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cornu Ammonis Changes Are at the Core of Hippocampal Pathology in Depression.","authors":"Darren Roddy,&nbsp;Veronica O'Keane","doi":"10.1177/2470547019849376","DOIUrl":"https://doi.org/10.1177/2470547019849376","url":null,"abstract":"<p><p>Commentary on: Roddy DW, Farrell C, Doolin K, Roman E, Tozzi L, Frodl T, O'Keane V, O'Hanlon E. The Hippocampus in Depression: More Than the Sum of Its Parts? Advanced Hippocampal Substructure Segmentation in Depression. Biol Psychiatry. 2019 Mar 15;85(6):487-497. doi: 10.1016/j.biopsych.2018.08.021. Epub 2018 Sep 6. PubMed PMID: 30528746. The hippocampus is a key cognitive hub implicated in major depressive disorder. However, major depressive disorder neuroimaging studies have used inconsistent anatomical hippocampal definitions to estimate hippocampal volumes, leading to some heterogeneity in findings. In a recent paper, we used a novel reassembly of automated hippocampal substructures (composites) to build alternative anatomical hippocampal definitions and used these to investigate differences in a well-defined cohort of major depressive disorder patients and healthy controls. We found that the most significant differences between major depressive disorder and healthy controls were localized to the core cornu ammonis (CA) regions of the hippocampus. The CA2-4 regions were smaller in first episode major depressive disorder, whereas more widespread differences were found in recurrent/chronic major depressive disorder, suggestive of a potential disease process in major depressive disorder. In this commentary, we also show how new hippocampal composites to investigate sections of the hippocampal circuitry demonstrate that differences in major depressive disorder occur across the input, middle and output circuit nodes of the hippocampal core. Hippocampal pathology localized across the core hippocampal CA circuity may account for the diverse and wide-ranging symptoms often experienced in depression.</p>","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":" ","pages":"2470547019849376"},"PeriodicalIF":0.0,"publicationDate":"2019-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2470547019849376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37962656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Open-Label Feasibility Trial Examining the Effectiveness of a Cognitive Training Program, Goal Management Training, in Individuals With Posttraumatic Stress Disorder.","authors":"Jenna E Boyd, Charlene O'Connor, Alina Protopopescu, Rakesh Jetly, Shawn G Rhind, Ruth A Lanius, Margaret C McKinnon","doi":"10.1177/2470547019841599","DOIUrl":"10.1177/2470547019841599","url":null,"abstract":"<p><strong>Background: </strong>Posttraumatic stress disorder (PTSD) is associated with dysfunction across multiple cognitive domains including executive functioning, attention, and verbal memory. This dysfunction is associated with negative impacts on functional outcomes (e.g., work or social functioning) and reduced response to psychotherapy for PTSD. Despite this knowledge, little work has investigated the efficacy of cognitive remediation strategies in improving cognition and functional outcomes among individuals with PTSD.</p><p><strong>Objective: </strong>The current study investigated the efficacy of an established cognitive remediation program, Goal Management Training (GMT), in improving cognitive functioning in a pilot sample of individuals with PTSD symptoms in an inpatient treatment setting.</p><p><strong>Method: </strong>Thirty-four inpatients with PTSD symptoms participated in either GMT in addition to treatment as usual (TAU; consisting of psychiatric management, group and individual psychotherapy) (TAU+GMT; <i>n</i> = 18) or TAU alone (<i>n = </i>16). The TAU+GMT group received neuropsychological assessment at baseline and posttreatment, while both the TAU+GMT and TAU groups received assessment with clinical self-report measures at baseline and posttreatment.</p><p><strong>Results: </strong>Paired-sample t-tests revealed significant improvements on measures of executive functioning (e.g., response inhibition, cognitive flexibility), processing speed, sustained attention, and verbal memory in the TAU+GMT group. Mixed-design analyses of variance (ANOVAs) revealed a trend toward an interaction effect indicating potentially greater improvements on a measure of the ability to engage in goal-directed behaviors while highly emotional in the TAU+GMT group as compared to the TAU group.</p><p><strong>Discussion: </strong>The results of this small feasibility investigation of GMT in PTSD point toward the potential efficacy of GMT in ameliorating cognitive difficulties in individuals with PTSD.</p>","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":" ","pages":"2470547019841599"},"PeriodicalIF":0.0,"publicationDate":"2019-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/40/10.1177_2470547019841599.PMC7219918.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37962128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Plasticity Induced by Ketamine in Human Dopaminergic Neurons as Mechanism Relevant for Treatment-Resistant Depression.","authors":"Ginetta Collo,&nbsp;Laura Cavalleri,&nbsp;Emilio Merlo Pich","doi":"10.1177/2470547019842545","DOIUrl":"https://doi.org/10.1177/2470547019842545","url":null,"abstract":"<p><p>The mechanisms underlying the antidepressant effects of ketamine in treatment-resistant depression are only partially understood. Reactivation of neural plasticity in prefrontal cortex has been considered critical in mediating the effects of standard antidepressants, but in treatment-resistant depression patients with severe anhedonia, other components of the affected brain circuits, for example, the dopamine system, could be involved. In a recent article in <i>Molecular Psychiatry</i>, we showed that ketamine induces neural plasticity in human and mouse dopaminergic neurons. Human dopaminergic neurons were differentiated from inducible pluripotent stem cells for over 60 days. Mimicking the pharmacokinetic exposures occurring in treatment-resistant depression subjects, cultures were incubated with either ketamine at 0.1 and 1 µM for 1 h or with its active metabolite (2R,6R)-hydroxynorketamine at 0.1 and 0.5 µM for up to 6 h. Three days after dosing, we observed a concentration-dependent increase in dendritic arborization and soma size. These effects were mediated by the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor that triggered the pathways of mammalian target of rapamycin and extracellular signal-regulated kinase via the engagement of brain-derived neurotrophic factor signaling, as previously described in rodent prefrontal cortex. Interestingly, we found that neural plasticity induced by ketamine requires functionally intact dopamine D3 receptors. These data are in keeping with our recent observation that plasticity can be induced in human dopaminergic neurons by the D3 receptor-preferential agonist pramipexole, whose effect as augmentation treatment in treatment-resistant depression has been reported. Overall, the evidence of pharmacologic response in human inducible pluripotent stem cell-derived neurons could provide complementary information to those provided by circuit-based imaging when assessing the potential response to a given augmentation treatment.</p>","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":" ","pages":"2470547019842545"},"PeriodicalIF":0.0,"publicationDate":"2019-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2470547019842545","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37962655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}