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neurogenesis psychiatry

A Carrard, M Elsayed, M Margineanu, B Boury-Jamot, L Fragnière, E M Meylan, J-M Petit, H Fiumelli, P J Magistretti, J-L Martin
In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment...
October 18, 2016: Molecular Psychiatry
S M Brooker, K T Gobeske, J Chen, C-Y Peng, J A Kessler
Many antidepressants stimulate adult hippocampal neurogenesis, but the mechanisms by which they increase neurogenesis and modulate behavior are incompletely understood. Here we show that hippocampal bone morphogenetic protein (BMP) signaling is modulated by antidepressant treatment, and that the changes in BMP signaling mediate effects of antidepressant treatment on neural progenitor cell proliferation and behavior. Treatment with the selective serotonin reuptake inhibitor fluoxetine suppressed BMP signaling in the adult mouse hippocampus both by decreasing levels of BMP4 ligand and increasing production of the BMP inhibitor noggin...
October 4, 2016: Molecular Psychiatry
S Riazuddin, M Hussain, A Razzaq, Z Iqbal, M Shahzad, D L Polla, Y Song, E van Beusekom, A A Khan, L Tomas-Roca, M Rashid, M Y Zahoor, W M Wissink-Lindhout, M A R Basra, M Ansar, Z Agha, K van Heeswijk, F Rasheed, M Van de Vorst, J A Veltman, C Gilissen, J Akram, T Kleefstra, M Z Assir, D Grozeva, K Carss, F L Raymond, T D O'Connor, S A Riazuddin, S N Khan, Z M Ahmed, A P M de Brouwer, H van Bokhoven, S Riazuddin
Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes...
July 26, 2016: Molecular Psychiatry
M C Marchetto, H Belinson, Y Tian, B C Freitas, C Fu, K C Vadodaria, P C Beltrao-Braga, C A Trujillo, A P D Mendes, K Padmanabhan, Y Nunez, J Ou, H Ghosh, R Wright, K J Brennand, K Pierce, L Eichenfield, T Pramparo, L T Eyler, C C Barnes, E Courchesne, D H Geschwind, F H Gage, A Wynshaw-Boris, A R Muotri
Autism spectrum disorders (ASD) are common, complex and heterogeneous neurodevelopmental disorders. Cellular and molecular mechanisms responsible for ASD pathogenesis have been proposed based on genetic studies, brain pathology and imaging, but a major impediment to testing ASD hypotheses is the lack of human cell models. Here, we reprogrammed fibroblasts to generate induced pluripotent stem cells, neural progenitor cells (NPCs) and neurons from ASD individuals with early brain overgrowth and non-ASD controls with normal brain size...
July 5, 2016: Molecular Psychiatry
M Fujitani, S Zhang, R Fujiki, Y Fujihara, T Yamashita
Chromosome 16p13.11 microduplication is a risk factor associated with various neurodevelopmental disorders such as attention-deficit/hyperactivity disorder, intellectual disabilities, developmental delay and autistic spectrum disorder. The underlying molecular mechanism of this genetic variation remained unknown, but its core genetic locus-conserved across mice and humans-contains seven genes. Here, we generated bacterial artificial chromosome-transgenic mice carrying a human 16p13.11 locus, and these mice showed the behavioral hyperactivity phenotype...
July 5, 2016: Molecular Psychiatry
Jack M Gorman
Many patients with depression, anxiety disorders, and other psychiatric disorders are treated with combinations of psychodynamic psychotherapy and medication. Whether this is better than monotherapy is an empirical question that requires much more extensive research than is currently available. When medications were first introduced to treat psychiatric illnesses, some psychopharmacologists insisted that it heralded a new area of "biological psychiatry" that would ultimately render psychotherapy obsolete. Psychodynamic theorists and practitioners, on the other hand, argued that psychopharmacology offered only a superficial approach to treatment...
2016: Psychodynamic Psychiatry
J F Costemale-Lacoste, J P Guilloux, R Gaillard
BACKGROUND: Since the discovery of antidepressants, new treatments have emerged with fewer side effects but no greater efficacy. Glycogen synthase kinase 3 β (GSK-3β), a kinase known for its activity on glycogen synthesis, has in the last few years raised growing interest in biological psychiatry. Several efficient treatments in major depression have an inhibitory effect on this kinase, which could be targeted in new mood disorder treatments. METHODS: The aim of this review is to summarize findings concerning the intracellular pharmacologic effects of GSK-3β inhibitors on mood...
April 2016: L'Encéphale
Ewa Ferensztajn-Rochowiak, Janusz K Rybakowski
Lithium has been used in modern psychiatry for more than 65 years, constituting a cornerstone for the long-term treatment of bipolar disorder. A number of biological properties of lithium have been discovered, including its hematological, antiviral and neuroprotective effects. In this article, a systematic review of the effect of lithium on hematopoietic, mesenchymal and neural stem cells is presented. The beneficial effects of lithium on the level of hematopoietic stem cells (HSC) and growth factors have been reported since 1970s...
April 2016: Pharmacological Reports: PR
I Hassouna, C Ott, L Wüstefeld, N Offen, R A Neher, M Mitkovski, D Winkler, S Sperling, L Fries, S Goebbels, I C Vreja, N Hagemeyer, M Dittrich, M F Rossetti, K Kröhnert, K Hannke, S Boretius, A Zeug, C Höschen, T Dandekar, E Dere, E Neher, S O Rizzoli, K-A Nave, A-L Sirén, H Ehrenreich
Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of ~20%...
January 26, 2016: Molecular Psychiatry
S Alboni, R M van Dijk, S Poggini, G Milior, M Perrotta, T Drenth, N Brunello, D P Wolfer, C Limatola, I Amrein, F Cirulli, L Maggi, I Branchi
Selective serotonin reuptake inhibitors (SSRIs) represent the most common treatment for major depression. However, their efficacy is variable and incomplete. In order to elucidate the cause of such incomplete efficacy, we explored the hypothesis positing that SSRIs may not affect mood per se but, by enhancing neural plasticity, render the individual more susceptible to the influence of the environment. Consequently, SSRI administration in a favorable environment promotes a reduction of symptoms, whereas in a stressful environment leads to a worse prognosis...
September 15, 2015: Molecular Psychiatry
B Readhead, J-V Haure-Mirande, B Zhang, V Haroutunian, S Gandy, E E Schadt, J T Dudley, M E Ehrlich
Identification and characterization of molecular mechanisms that connect genetic risk factors to initiation and evolution of disease pathophysiology represent major goals and opportunities for improving therapeutic and diagnostic outcomes in Alzheimer's disease (AD). Integrative genomic analysis of the human AD brain transcriptome holds potential for revealing novel mechanisms of dysfunction that underlie the onset and/or progression of the disease. We performed an integrative genomic analysis of brain tissue-derived transcriptomes measured from two lines of mice expressing distinct mutant AD-related proteins...
August 2016: Molecular Psychiatry
Oliwia Gawlik-Kotelnicka, Wojciech Mielicki, Jolanta Rabe-Jabłońska, Dominik Strzelecki
Objectives Lithium may inhibit lipid peroxidation (LP) and protein oxidation, stimulate cell proliferation, increase neurogenesis, and delay cell death. Oxidative stress (OxS) is a state of imbalance between oxidative processes and antioxidant defenses, which may play an important role in the pathophysiology and disease course of bipolar disorder (BD). The aim of this study was to estimate the influence of lithium, administered alone or in combination with haloperidol, on selected OxS parameters in human plasma in vitro...
July 20, 2015: Redox Report: Communications in Free Radical Research
Eugene L Dimitrov, Mumeko C Tsuda, Heather A Cameron, Ted B Usdin
Pain and depression are frequently associated with and often persist after resolution of an initial injury. Identifying the extent to which depression remains causally associated with ongoing physical discomfort during chronic pain, or becomes independent of it, is an important problem for basic neuroscience and psychiatry. Difficulty in distinguishing between effects of ongoing aversive sensory input and its long-term consequences is a significant roadblock, especially in animal models. To address this relationship between localized physical discomfort and its more global consequences, we investigated cellular and behavioral changes during and after reversing a mouse model of neuropathic pain...
September 10, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Greg T Sutherland, Donna Sheedy, Jillian J Kril
The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD)...
January 2014: Alcoholism, Clinical and Experimental Research
E Kolshus, V S Dalton, K M Ryan, D M McLoughlin
OBJECTIVE: MicroRNAs are small non-coding RNA molecules that regulate gene expression, including genes involved in neuronal function and plasticity that have relevance for brain function and mental health. We therefore performed a systematic review of miRNAs in general adult psychiatric disorders. METHOD: Systematic searches in PubMed/MEDLINE and Web of Science were conducted to identify published clinical articles on microRNAs in general adult psychiatric disorders...
April 2014: Acta Psychiatrica Scandinavica
Robert H Howland
Metformin, currently approved for the treatment of type 2 diabetes, is an interesting drug that has various cellular and molecular mechanisms. These mechanisms have justified other off-label clinical and investigational uses for diabetes prevention in high-risk patients, for polycystic ovary syndrome, non-diabetic obesity, non-alcoholic fatty liver disease, and for prevention or treatment of cancer. A large number of controlled and uncontrolled studies have generally found metformin to be effective, well tolerated, and safe for preventing or treating antipsychotic-related weight gain and for improving metabolic abnormalities in psychiatric patient populations...
September 2013: Journal of Psychosocial Nursing and Mental Health Services
Mee-Sook Song, Dmitriy Matveychuk, Erin M MacKenzie, Maryana Duchcherer, Darrell D Mousseau, Glen B Baker
Although not used as extensively as other antidepressants for the treatment of depression, the monoamine oxidase (MAO) inhibitors continue to hold a niche in psychiatry and to have a relatively broad spectrum with regard to treatment of psychiatric and neurological disorders. Experimental and clinical research on MAO inhibitors has been expanding in the past few years, primarily because of exciting findings indicating that these drugs have neuroprotective properties (often independently of their ability to inhibit MAO)...
July 2013: Progress in Neuro-psychopharmacology & Biological Psychiatry
R Andrew Chambers
BACKGROUND: As knowledge deepens about how new neurons are born, differentiate, and wire into the adult mammalian brain, growing evidence depicts hippocampal neurogenesis as a special form of neuroplasticity that may be impaired across psychiatric disorders. This review provides an integrated-evidence based framework describing a neurogenic basis for addictions and addiction vulnerability in mental illness. METHODS: Basic studies conducted over the last decade examining the effects of addictive drugs on adult neurogenesis and the impact of neurogenic activity on addictive behavior were compiled and integrated with relevant neurocomputational and human studies...
June 1, 2013: Drug and Alcohol Dependence
O Riccio, M Jacobshagen, B Golding, L Vutskits, D Jabaudon, J P Hornung, A G Dayer
The serotonin transporter (SERT) is a key molecule involved in the homeostasis of extracellular levels of serotonin and is regulated developmentally. Genetic deletion of SERT in rodents increases extracellular levels of serotonin and affects cellular processes involved in neocortical circuit assembly such as barrel cortex wiring and cortical interneuron migration. Importantly, pharmacological blockade of SERT during brain development leads to phenotypes relevant to psychiatry in rodents and to an increased risk for autism spectrum disorders in humans...
2011: Translational Psychiatry
Silvia Wikinski
This work summarizes the efforts made in the last twenty years towards the discovery of the physiopathogeny of mental diseases. It takes the "case" of major depression and reviews the different theories proposed to explain its physiopathogeny beginning with the role of excitatory aminoacids, glucocorticoids and trophic neurofactors in the '90s, the neurogenesis at the beginning of '00s and the genetics, the epigenetics and the research on neural networks in the last years. Result of these scientific efforts seem to be a construction which has at the same time the strength of the evidences employed in its building and the weakness that emerges from the reductionism necessary to obtain them...
November 2011: Vertex: Revista Argentina de Psiquiatriá
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