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Resistant major depression

Ruin Moaddel, Michelle Shardell, Mohammed Khadeer, Jacqueline Lovett, Bashkim Kadriu, Sarangan Ravichandran, Patrick J Morris, Peixiong Yuan, Craig J Thomas, Todd D Gould, Luigi Ferrucci, Carlos A Zarate
(R,S)-Ketamine produces rapid, robust, and sustained antidepressant effects in major depressive disorder. Specifically, its pharmacological efficacy in treatment refractory depression is considered a major breakthrough in the field. However, the mechanism of action of ketamine's rapid effect remains to be determined. In order to identify pathways that are responsible for ketamine's effect, a targeted metabolomic approach was carried out using a double-blind, placebo-controlled crossover design, with infusion order randomized with medication-free patients with treatment-resistant major depressive disorder (29 subjects) and healthy controls (25 subjects)...
August 16, 2018: Psychopharmacology
Sarah Nicolas, Delphine Debayle, Catherine Béchade, Luc Maroteaux, Anne-Sophie Gay, Pascale Bayer, Catherine Heurteaux, Alice Guyon, Joëlle Chabry
Major depression is a psychiatric disorder with complex etiology. About 30% of depressive patients are resistant to antidepressants that are currently available, likely because they only target the monoaminergic systems. Thus, identification of novel antidepressants with a larger action spectrum is urgently required. Epidemiological data indicate high comorbidity between metabolic and psychiatric disorders, particularly obesity and depression. We used a well-characterized anxiety/depressive-like mouse model consisting of continuous input of corticosterone for seven consecutive weeks...
August 16, 2018: Translational Psychiatry
Gianluca Serafini, Giulia Adavastro, Giovanna Canepa, Domenico De Berardis, Alessandro Valchera, Maurizio Pompili, Henry Nasrallah, Mario Amore
Although several pharmacological options to treat depression are currently available, approximately one third of patients who receive antidepressant medications do not respond adequately or achieve a complete remission. Thus, novel strategies are needed to successfully address those who did not respond, or partially respond, to available antidepressant pharmacotherapy. Research findings revealed that the opioid system is significantly involved in the regulation of mood and incentives salience and may be an appropriate target for novel therapeutic agents...
August 15, 2018: International Journal of Molecular Sciences
Rafael Ferreira-Garcia, Rafael Christophe da Rocha Freire, José Carlos Appolinário, Michelle N Levitan, Roseane Dorte Halkjær-Lassen, João Romildo Bueno, Antonio E Nardi
BACKGROUND: Few therapeutic options are available for patients with electroconvulsive therapy-resistant major depressive disorder (ECT-r MDD), leaving a substantial proportion of this population beyond treatment possibilities. The combination of monoamine oxidase inhibitors and tricyclic antidepressants could be a potential strategy for managing ECT-r MDD, and the specific association of amitriptyline and tranylcypromine may offer additional tolerability advantages. Although promising, in our knowledge, no studies have examined until now the effectiveness of this combination in ECT-r MDD...
August 14, 2018: Journal of Clinical Psychopharmacology
Yawei Si, Zhenhua Song, Xiaoyan Sun, Jin-Hui Wang
Major depression in negative mood is presumably induced by chronic stress with lack of reward. However, most individuals who experience chronic stress demonstrate resilience. Molecular mechanisms underlying stress- induced depression versus resilience remain unknown, which are investigated in brain reward circuits. Mice were treated by chronic unpredictable mild stress (CUMS) for 4 weeks. The tests of sucrose preference, Y-maze, and forced swimming were used to identify depression-like emotion behavior or resilience...
August 14, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Hiroaki Hori, Seiji Nakamura, Fuyuko Yoshida, Toshiya Teraishi, Daimei Sasayama, Miho Ota, Kotaro Hattori, Yoshiharu Kim, Teruhiko Higuchi, Hiroshi Kunugi
Etiology of depression and its vulnerability remains elusive. Using a latent profile analysis on dimensional personality traits, we previously identified 3 different phenotypes in the general population, namely stress-resilient, -vulnerable, and -resistant groups. Here we performed microarray-based blood gene expression profiling of these 3 groups (n = 20 for each group) in order to identify genes involved in stress vulnerability as it relates to the risk of depression. Identified differentially expressed genes among the groups were most markedly enriched in ribosome-related pathways...
August 6, 2018: Journal of Psychiatric Research
Elizabeth D Ballard, Julia S Yarrington, Cristan A Farmer, Erica Richards, Rodrigo Machado-Vieira, Bashkim Kadriu, Mark J Niciu, Peixiong Yuan, Lawrence Park, Carlos A Zarate
BACKGROUND: No pharmacological treatments exist for active suicidal ideation (SI), but the glutamatergic modulator ketamine elicits rapid changes in SI. We developed data-driven subgroups of SI trajectories after ketamine administration, then evaluated clinical, demographic, and neurobiological factors that might predict SI response to ketamine. METHODS: Data were pooled from five clinical ketamine trials. Treatment-resistant inpatients (n = 128) with DSM-IV-TR-diagnosed major depressive disorder (MDD) or bipolar depression received one subanesthetic (0...
July 30, 2018: Journal of Affective Disorders
Sarah L Garnaat, Shiwen Yuan, Haizhi Wang, Noah S Philip, Linda L Carpenter
Transcranial magnetic stimulation has emerged as a treatment option for treatment-resistant depression. While existing data largely support efficacy of transcranial magnetic stimulation for major depressive disorder, ongoing research aims to optimize treatment parameters and identify biomarkers of treatment response. In this article, the authors describe data from controlled trials and ongoing efforts to enhance transcranial magnetic stimulation outcomes for major depressive disorder. Findings from preliminary research aimed at identifying neuroimaging and neurophysiological biomarkers of transcranial magnetic stimulation effects are discussed...
September 2018: Psychiatric Clinics of North America
Reuben Chukwuka Okocha, Isaac Olufemi Olatoye, Olufemi Bolarinwa Adedeji
Background: Residues of antimicrobials in food have received much attention in recent years because of growing food safety and public health concerns. Their presence in food of animal origin constitutes socioeconomic challenges in international trade in animal and animal products. The major public health significances of antimicrobial residues include the development of antimicrobial drug resistance, hypersensitivity reaction, carcinogenicity, mutagenicity, teratogenicity, bone marrow depression, and disruption of normal intestinal flora...
2018: Public Health Reviews
Brice Le François, Lei Zhang, Gouri J Mahajan, Craig A Stockmeier, Eitan Friedman, Paul R Albert
The serotonin-1A (5-HT1A) receptor is a key regulator of serotonergic activity and is implicated in mood and emotion. However, its post-transcriptional regulation has never been studied in humans. In the present study, we show that the "intronless" human 5-HT1A gene (HTR1A) is alternatively spliced in its 3'-UTR, yielding two novel splice variants. These variants lack a ∼1.6-kb intron, which contains a miR135 target site. Unlike the human HTR1A, splicing was not detected in the mouse HTR1A, which lacks the splice donor/accepter sites...
August 7, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Antoine Yrondi, Bruno Aouizerate, Wissam El-Hage, Fanny Moliere, Claire Thalamas, Nicolas Delcourt, Marie Sporer, Simon Taib, Laurent Schmitt, Nicolas Arlicot, Deborah Meligne, Agnes Sommet, Anne S Salabert, Sebastien Guillaume, Philippe Courtet, Florence Galtier, Denis Mariano-Goulart, Nicolas Menjot De Champfleur, Emmanuelle Le Bars, Thomas Desmidt, Mathieu Lemaire, Vincent Camus, Maria J Santiago-Ribeiro, Jean P Cottier, Philippe Fernandez, Marie Meyer, Vincent Dousset, Olivier Doumy, Didier Delhaye, Lucile Capuron, Marion Leboyer, Emmanuel Haffen, Patrice Péran, Pierre Payoux, Christophe Arbus
Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4-20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans...
2018: Frontiers in Psychiatry
G Fond, M Faugere, C Faget-Agius, M Cermolacce, R Richieri, L Boyer, C Lançon
Hypovitaminosis D has been associated with, respectively, major depressive disorder, schizophrenia (SZ), and cognitive disorders in the general population, and with positive and negative symptoms and metabolic syndrome in schizophrenia. The objective was to determine the prevalence of hypovitaminosis D and associated factors in a non-selected multicentric sample of SZ subjects in day hospital. Hypovitaminosis D was defined by blood vitamin D level < 25 nM. Depressive symptoms were assessed by the Calgary Depression Rating Scale Score and Positive and Negative Syndrome Scale Score...
August 4, 2018: European Archives of Psychiatry and Clinical Neuroscience
Marc J Weigensberg, Donna Spruijt-Metz, Cheng K Fred Wen, Jaimie N Davis, Quintilia Àvila, Magaly Juarez, Niquelle Brown Wadé, Christianne J Lane
Innovative lifestyle interventions are needed to reduce type 2 diabetes risk in adolescents. This report describes the protocol of the Imagine HEALTH cluster randomized control trial, that tests an intervention based in Self-Determination Theory (SDT) and uses lifestyle education combined with the mind-body, complementary health modality of guided imagery (GI), to address obesity prevention and treatment in predominantly Latino adolescents. The primary aim is to determine the unique effects of each of the three major components of the 12-week lifestyle intervention (lifestyle education, stress reduction guided imagery, and lifestyle behavior guided imagery) compared to control on primary outcomes of physical activity (accelerometry), dietary intake (3-day recall), and stress biomarker levels (salivary cortisol)...
August 1, 2018: Contemporary Clinical Trials
Mladen Golubić, Dana Schneeberger, Kristin Kirkpatrick, Judi Bar, Adam Bernstein, Fredina Weems, Jane Ehrman, Jim Perko, Jonathan Doyle, Michael Roizen
OBJECTIVES: Healthy lifestyle modifications, including weight management, regular physical activity, prudent diet, and stress relief, have been identified as key components of tertiary cancer prevention. In this study, we evaluate the effectiveness of a comprehensive, lifestyle medicine intervention, Lifestyle 180® , on chronic disease risk factors and quality of life in cancer survivors. DESIGN: Retrospective subgroup analysis of a clinical program. SETTINGS/LOCATION: An outpatient medical facility...
August 1, 2018: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
Lili Hou, Min Zhang, Xingyi Zhang, Zhenwei Liu, Pengyu Zhang, Dongying Qiu, Lei Zhu, Xin Zhou
The airway vagal preganglionic neurons (AVPNs) providing projections to intrinsic tracheobronchial ganglia are considered to be crucial to modulation of airway resistance in physiological and pathological states. AVPNs classified into inspiratory-activated AVPNs (IA-AVPNs) and inspiratory-inhibited AVPNs (II-AVPNs) are regulated by thyrotropin-releasing hormone (TRH)-containing terminals. TRH causes a direct excitatory current and attenuates the phasic inspiratory glycinergic inputs in II-AVPNs, however, whether and how TRH influences IA-AVPNs remains unknown...
2018: Frontiers in Physiology
Valentina Puglisi, Alessia Bramanti, Giuseppe Lanza, Mariagiovanna Cantone, Luisa Vinciguerra, Manuela Pennisi, Lilla Bonanno, Giovanni Pennisi, Rita Bella
Introduction: Late-life depression is a well-known risk factor for future dementia. Increasing evidences also show a link between cerebral hypoperfusion and neurodegeneration, although data on Transcranial Doppler ultrasonography (TCD)-derived measures in patients with "Vascular Depression" (VD) are lacking. The aim of this study was to assess and correlate TCD parameters with cognitive function and severity of subcortical ischemic vascular disease in a sample of VD patients. Methods: Seventy six patients (mean age 72...
2018: Frontiers in Psychiatry
Carla Nasca, Benedetta Bigio, Francis S Lee, Sarah P Young, Marin M Kautz, Ashly Albright, James Beasley, David S Millington, Aleksander A Mathé, James H Kocsis, James W Murrough, Bruce S McEwen, Natalie Rasgon
The lack of biomarkers to identify target populations greatly limits the promise of precision medicine for major depressive disorder (MDD), a primary cause of ill health and disability. The endogenously produced molecule acetyl-l-carnitine (LAC) is critical for hippocampal function and several behavioral domains. In rodents with depressive-like traits, LAC levels are markedly decreased and signal abnormal hippocampal glutamatergic function and dendritic plasticity. LAC supplementation induces rapid and lasting antidepressant-like effects via epigenetic mechanisms of histone acetylation...
July 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Cancan He, Liang Gong, Yingying Yin, Yonggui Yuan, Haisan Zhang, Luxian Lv, Xiangyang Zhang, Jair C Soares, Hongxing Zhang, Chunming Xie, Zhijun Zhang
Anxiety is the most frequently co-occurring symptom with depression and subsequently contributes to increased severity and treatment resistance in patients with major depressive disorder (MDD). However, little is known about how these two behaviors are linked or interact at the neural network level. Seventy-five unmedicated MDD patients and 42 cognitively normal (CN) subjects underwent resting-state functional magnetic resonance imaging (R-fMRI) and neuropsychological testing. Multivariate linear regression analysis was performed to investigate the neural substrates of anxiety and depression, as well as their interactive effects on the amygdala functional connectivity (AFC) network in MDD patients...
July 27, 2018: Brain Imaging and Behavior
Rajamannar Ramasubbu, Stefan Lang, Zelma H T Kiss
Background: The electrical parameters used for deep brain stimulation (DBS) in movement disorders have been relatively well studied, however for the newer indications of DBS for psychiatric indications these are less clear. Based on the movement disorder literature, use of the correct stimulation parameters should be crucial for clinical outcomes. This review examines the stimulation parameters used in DBS studies for treatment resistant depression (TRD) and their relevance to clinical outcome and brain targets...
2018: Frontiers in Psychiatry
Maurizio Fava, Suresh Durgam, Willie Earley, Kaifeng Lu, Robert Hayes, István Laszlovszky, György Németh
This 19-week, double-blind, placebo-controlled, randomized phase 2 study evaluated the efficacy, safety, and tolerability of adjunctive cariprazine (0.1-0.3 and 1.0-2.0 mg/day) as an antidepressant treatment for adults with treatment-resistant major depressive disorder (MDD) (NCT00854100). The primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score and the secondary was change in the Clinical Global Impression-Intensity score. Additional efficacy parameters were also assessed...
July 24, 2018: International Clinical Psychopharmacology
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