Brain-derived neurotrophic factor in mood disorders and antidepressant treatments

Levels of brain-derived neurotrophic factor (BDNF) are reduced in the brain and serum of depressed patients and at least the reduction in serum levels is reversible upon successful treatment. These data, together with a wealth of reports using different animal models with depression-like behavior or manipulation of expression of BDNF or its receptor TrkB have implicated BDNF in the pathophysiology of depression as well as in the mechanism of action of antidepressant treatments. Recent findings have shown that posttranslational processing of BDNF gene product can yield different molecular entities that differently influence signaling through BNDF receptor TrkB and the pan-neurotrophin receptor p75NTR. We will here review these data and discuss new insights into the possible pathophysiological roles of those new BDNF subtypes as well as recent findings on the role of BDNF mediated neuronal plasticity in mood disorders and their treatments.

[1]  J. Talbott Combined Prolonged Exposure Therapy and Paroxetine for PTSD Related to the World Trade Center Attack: A Randomized Controlled Trial , 2013 .

[2]  J. Krystal,et al.  Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. , 2015, Annual review of medicine.

[3]  B. Franke,et al.  Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity , 2010, Molecular Psychiatry.

[4]  Daniel S Spellman,et al.  Neuronal Growth Cone Retraction Relies on Proneurotrophin Receptor Signaling Through Rac , 2011, Science Signaling.

[5]  Barbara L. Hempstead,et al.  Regulation of Cell Survival by Secreted Proneurotrophins , 2001, Science.

[6]  Martin Korte,et al.  Form follows function: BDNF and its involvement in sculpting the function and structure of synapses , 2014, Neuropharmacology.

[7]  Nanxin Li,et al.  mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists , 2010, Science.

[8]  T. Miyakawa,et al.  Immature Dentate Gyrus: An Endophenotype of Neuropsychiatric Disorders , 2013, Neural plasticity.

[9]  M. Barrot,et al.  Essential role of brain-derived neurotrophic factor in adult hippocampal function. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  N. Karpova Role of BDNF epigenetics in activity-dependent neuronal plasticity , 2014, Neuropharmacology.

[11]  M. Huntsman,et al.  BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: Temporal patterns of induction distinct from NGF , 1991, Neuron.

[12]  Petti T. Pang,et al.  The yin and yang of neurotrophin action , 2005, Nature Reviews Neuroscience.

[13]  E. Kavalali,et al.  NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses , 2011, Nature.

[14]  N. Greig,et al.  Roles of p75NTR, Long-Term Depression, and Cholinergic Transmission in Anxiety and Acute Stress Coping , 2012, Biological Psychiatry.

[15]  S. Gabriel,et al.  Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus , 2002, Molecular Psychiatry.

[16]  F. Lee,et al.  Val66Met Polymorphism of BDNF Alters Prodomain Structure to Induce Neuronal Growth Cone Retraction , 2013, Nature Communications.

[17]  J. Siuciak,et al.  Hippocampal mossy fiber sprouting induced by chronic electroconvulsive seizures , 1999, Neuroscience.

[18]  Bai Lu,et al.  Activation of p75NTR by proBDNF facilitates hippocampal long-term depression , 2005, Nature Neuroscience.

[19]  Y. Barde,et al.  Characterisation of neurotrophin dimers and monomers. , 1994, European journal of biochemistry.

[20]  M. Webster,et al.  Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. , 2011, Journal of psychiatry & neuroscience : JPN.

[21]  A. Zangen,et al.  Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis , 2009, Molecular Psychiatry.

[22]  E. Castrén,et al.  Enhanced BDNF Signaling is Associated with an Antidepressant-like Behavioral Response and Changes in Brain Monoamines , 2005, Cellular and Molecular Neurobiology.

[23]  C. Léránth,et al.  Remodeling of Hippocampal Spine Synapses in the Rat Learned Helplessness Model of Depression , 2009, Biological Psychiatry.

[24]  M. Garabedian,et al.  Activation of Trk neurotrophin receptors by glucocorticoids provides a neuroprotective effect , 2008, Proceedings of the National Academy of Sciences.

[25]  S. Yamawaki,et al.  BDNF pro-peptide actions facilitate hippocampal LTD and are altered by the common BDNF polymorphism Val66Met , 2015, Proceedings of the National Academy of Sciences.

[26]  E. Castrén,et al.  Fear Erasure in Mice Requires Synergy Between Antidepressant Drugs and Extinction Training , 2011, Science.

[27]  Y. Barde,et al.  Brain-derived Neurotrophic Factor in Megakaryocytes*♦ , 2016, The Journal of Biological Chemistry.

[28]  Petti T. Pang,et al.  Cleavage of proBDNF by tPA/Plasmin Is Essential for Long-Term Hippocampal Plasticity , 2004, Science.

[29]  M. Berk,et al.  Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications , 2014, Molecular Psychiatry.

[30]  Y. Okamoto,et al.  DNA Methylation Profiles of the Brain-Derived Neurotrophic Factor (BDNF) Gene as a Potent Diagnostic Biomarker in Major Depression , 2011, PloS one.

[31]  M. Riva,et al.  Neuronal plasticity: A link between stress and mood disorders , 2009, Psychoneuroendocrinology.

[32]  Ruoyan Chen,et al.  Brain-derived Neurotrophic Factor Is Stored in Human Platelets and Released by Agonist Stimulation , 2002, Thrombosis and Haemostasis.

[33]  L. Maffei,et al.  The Antidepressant Fluoxetine Restores Plasticity in the Adult Visual Cortex , 2008, Science.

[34]  M. Riva,et al.  Acute Stress Responsiveness of the Neurotrophin BDNF in the Rat Hippocampus is Modulated by Chronic Treatment with the Antidepressant Duloxetine , 2009, Neuropsychopharmacology.

[35]  J. Deakin,et al.  Expression of hippocampal brain-derived neurotrophic factor and its receptors in Stanley consortium brains. , 2009, Journal of psychiatric research.

[36]  E. Nestler,et al.  A molecular and cellular theory of depression. , 1997, Archives of general psychiatry.

[37]  Ronald S Duman,et al.  Cell Proliferation in Adult Hippocampus is Decreased by Inescapable Stress: Reversal by Fluoxetine Treatment , 2003, Neuropsychopharmacology.

[38]  C. Altar Neurotrophins and depression. , 1999, Trends in pharmacological sciences.

[39]  T. Werge,et al.  Interaction between genetic polymorphisms and stressful life events in first episode depression. , 2009, Journal of affective disorders.

[40]  K. Wittfeld,et al.  Neuroscience and Biobehavioral Reviews Review Bdnf Val66met Polymorphism and Hippocampal Volume in Neuropsychiatric Disorders: a Systematic Review and Meta-analysis , 2022 .

[41]  K. Hashimoto,et al.  Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism , 2006, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[42]  Zachary S. Lorsch,et al.  Essential Role of Mesolimbic Brain-Derived Neurotrophic Factor in Chronic Social Stress–Induced Depressive Behaviors , 2016, Biological Psychiatry.

[43]  K. Bath,et al.  BDNF Val66Met Impairs Fluoxetine-Induced Enhancement of Adult Hippocampus Plasticity , 2012, Neuropsychopharmacology.

[44]  J. Os,et al.  The size and burden of mental disorders and other disorders of the brain in Europe 2010 , 2011, European Neuropsychopharmacology.

[45]  M. Chao,et al.  Are BDNF and glucocorticoid activities calibrated? , 2013, Neuroscience.

[46]  E. Nestler,et al.  Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action , 2006, Nature Neuroscience.

[47]  Yogesh K. Dwivedi,et al.  Neurotrophin Receptor Activation and Expression in Human Postmortem Brain: Effect of Suicide , 2009, Biological Psychiatry.

[48]  H. Manji,et al.  New insights into BDNF function in depression and anxiety , 2007, Nature Neuroscience.

[49]  Scott J. Russo,et al.  Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions , 2007, Cell.

[50]  C. Cotman,et al.  Exercise, Antidepressant Medications, and Enhanced Brain Derived Neurotrophic Factor Expression , 1999, Neuropsychopharmacology.

[51]  H. Thoenen,et al.  Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non‐NMDA glutamate receptors. , 1990, The EMBO journal.

[52]  R. Hen,et al.  Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants , 2003, Science.

[53]  G. MacQueen,et al.  Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression. , 2001, Behavioral neuroscience.

[54]  M. Götz,et al.  Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior , 2008, Proceedings of the National Academy of Sciences.

[55]  Yong-Ku Kim,et al.  Reduced platelet BDNF level in patients with major depression , 2009, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[56]  I. Lucki,et al.  Central administration of IGF-I and BDNF leads to long-lasting antidepressant-like effects , 2005, Brain Research.

[57]  B. Hempstead,et al.  Induction of Proneurotrophins and Activation of p75NTR-Mediated Apoptosis via Neurotrophin Receptor-Interacting Factor in Hippocampal Neurons after Seizures , 2008, The Journal of Neuroscience.

[58]  M. Riva,et al.  Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine , 2011, Psychopharmacology.

[59]  E. Castrén,et al.  Neuronal plasticity and antidepressant actions , 2013, Trends in Neurosciences.

[60]  H. Thoenen Neurotrophins and Neuronal Plasticity , 1995, Science.

[61]  W. Kuang,et al.  Brain‐derived neurotrophic factor Val66Met polymorphism association with antidepressant efficacy: A systematic review and meta‐analysis , 2014, Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists.

[62]  L. Monteggia,et al.  Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders , 2012, Pharmacological Reviews.

[63]  F. McMahon,et al.  Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Antidepressant Efficacy of Ketamine in Depressed Patients , 2012, Biological Psychiatry.

[64]  Danielle L. Graham,et al.  Essential Role of BDNF in the Mesolimbic Dopamine Pathway in Social Defeat Stress , 2006, Science.

[65]  E. Castrén Neuronal network plasticity and recovery from depression. , 2013, JAMA psychiatry.

[66]  B. Carter,et al.  The biological functions and signaling mechanisms of the p75 neurotrophin receptor. , 2014, Handbook of experimental pharmacology.

[67]  Hironori Ito,et al.  Age-related changes in BDNF protein levels in human serum: differences between autism cases and normal controls , 2007, International Journal of Developmental Neuroscience.

[68]  E. Castrén,et al.  Is mood chemistry? , 2005, Nature Reviews Neuroscience.

[69]  E. Sibille,et al.  Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder. , 2012, The American journal of psychiatry.

[70]  M. Frotscher,et al.  Jcb: Article , 2022 .

[71]  Kevin G Bath,et al.  Variant BDNF (Val66Met) impact on brain structure and function , 2006, Cognitive, affective & behavioral neuroscience.

[72]  E. Castrén,et al.  The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity , 2010, Developmental neurobiology.

[73]  E. Castrén,et al.  Role of Brain-Derived Neurotrophic Factor in the Aetiology of Depression , 2010, CNS drugs.

[74]  Rene Hen,et al.  Adult hippocampal neurogenesis in depression , 2007, Nature Neuroscience.

[75]  M. Riva,et al.  Chronic Duloxetine Treatment Induces Specific Changes in the Expression of BDNF Transcripts and in the Subcellular Localization of the Neurotrophin Protein , 2007, Neuropsychopharmacology.

[76]  Y. Kubota,et al.  Structural basis for the role of inhibition in facilitating adult brain plasticity , 2011, Nature Neuroscience.

[77]  S. Radka,et al.  Presence of brain-derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay , 1996, Brain Research.

[78]  M. Chao,et al.  Trk receptors. , 2014, Handbook of experimental pharmacology.

[79]  N. Sousa,et al.  The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling , 2009, Molecular Psychiatry.

[80]  M. Egan,et al.  The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function , 2003, Cell.

[81]  F. McMahon,et al.  Brain-derived neurotrophic factor ( BDNF) gene: no major impact on antidepressant treatment response. , 2009, The international journal of neuropsychopharmacology.

[82]  N. Gervasoni,et al.  Low Brain-Derived Neurotrophic Factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity , 2005, Biological Psychiatry.

[83]  E. Castrén,et al.  Mice with altered BDNF signaling as models for mood disorders and antidepressant effects , 2014, Front. Behav. Neurosci..

[84]  R. Hen,et al.  Chronic Fluoxetine Stimulates Maturation and Synaptic Plasticity of Adult-Born Hippocampal Granule Cells , 2008, The Journal of Neuroscience.

[85]  R. Rodriguiz,et al.  Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice , 2013, Proceedings of the National Academy of Sciences.

[86]  B. Dias,et al.  Differential regulation of Brain Derived Neurotrophic Factor transcripts by antidepressant treatments in the adult rat brain , 2003, Neuropharmacology.

[87]  L. Maffei,et al.  Experience‐dependent expression of NPAS4 regulates plasticity in adult visual cortex , 2012, The Journal of physiology.

[88]  A. Ogura,et al.  Multiple functions of precursor BDNF to CNS neurons: negative regulation of neurite growth, spine formation and cell survival , 2009, Molecular Brain.

[89]  C. Zarate,et al.  Antidepressant actions of ketamine: from molecular mechanisms to clinical practice , 2015, Current Opinion in Neurobiology.

[90]  Sudha Seshadri,et al.  Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham Heart Study. , 2014, JAMA neurology.

[91]  R. Duman,et al.  Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[92]  T. Lehtimäki,et al.  Interaction between 5-HT1A and BDNF genotypes increases the risk of treatment-resistant depression , 2007, Journal of Neural Transmission.

[93]  E. Tongiorgi,et al.  A method for reproducible measurements of serum BDNF: comparison of the performance of six commercial assays , 2015, Scientific Reports.

[94]  Amelia Russo-Neustadt,et al.  Physical activity–antidepressant treatment combination: impact on brain-derived neurotrophic factor and behavior in an animal model , 2001, Behavioural Brain Research.

[95]  T. Insel,et al.  The STAR*D trial: revealing the need for better treatments. , 2009, Psychiatric services.

[96]  T. Dinan,et al.  Serum BDNF as a peripheral biomarker of treatment-resistant depression and the rapid antidepressant response: A comparison of ketamine and ECT. , 2015, Journal of affective disorders.

[97]  C. Siao,et al.  Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related Behavior , 2006, Science.

[98]  R. Duman,et al.  A Neurotrophic Model for Stress-Related Mood Disorders , 2006, Biological Psychiatry.

[99]  T. Zetterström,et al.  Bi-phasic change in BDNF gene expression following antidepressant drug treatment , 2003, Neuropharmacology.

[100]  T. Timmusk,et al.  Identification of cis-Elements and Transcription Factors Regulating Neuronal Activity-Dependent Transcription of Human BDNF Gene , 2011, The Journal of Neuroscience.

[101]  G. Aghajanian,et al.  Brain-Derived Neurotrophic Factor Val66Met Allele Impairs Basal and Ketamine-Stimulated Synaptogenesis in Prefrontal Cortex , 2012, Biological Psychiatry.

[102]  T. Miyakawa,et al.  Reversal of hippocampal neuronal maturation by serotonergic antidepressants , 2010, Proceedings of the National Academy of Sciences.

[103]  Interaction between stress and the BDNF Val66Met polymorphism in depression: A systematic review and meta-analysis , 2014 .

[104]  E. Castrén,et al.  Pharmacologically Diverse Antidepressants Rapidly Activate Brain-Derived Neurotrophic Factor Receptor TrkB and Induce Phospholipase-Cγ Signaling Pathways in Mouse Brain , 2007, Neuropsychopharmacology.

[105]  L. Maffei,et al.  Serotonin triggers a transient epigenetic mechanism that reinstates adult visual cortex plasticity in rats , 2011, The European journal of neuroscience.

[106]  G. MacQueen,et al.  Increased hippocampal bdnf immunoreactivity in subjects treated with antidepressant medication , 2001, Biological Psychiatry.

[107]  A. Serretti,et al.  Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder , 2010, Molecular Psychiatry.

[108]  N. Seidah,et al.  Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases , 1996, FEBS letters.

[109]  K. Bath,et al.  Variant BDNF Val66Met Polymorphism Affects Extinction of Conditioned Aversive Memory , 2009, The Journal of Neuroscience.

[110]  K. Hashimoto,et al.  Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants , 2003, Biological Psychiatry.

[111]  M. Riva,et al.  Serum and plasma BDNF levels in major depression: A replication study and meta-analyses , 2010, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[112]  M. Barrot,et al.  Brain-derived neurotrophic factor in the ventral midbrain–nucleus accumbens pathway: a role in depression , 2003, Biological Psychiatry.

[113]  M. Meyer,et al.  Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[114]  E. Castrén,et al.  Co-Treatment with Diazepam Prevents the Effects of Fluoxetine on the Proliferation and Survival of Hippocampal Dentate Granule Cells , 2009, Biological Psychiatry.

[115]  M. Banasr,et al.  BDNF Release Is Required for the Behavioral Actions of Ketamine , 2014, The international journal of neuropsychopharmacology.

[116]  R. Kvetňanský,et al.  Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[117]  Mikko Sairanen,et al.  Brain-Derived Neurotrophic Factor and Antidepressant Drugs Have Different But Coordinated Effects on Neuronal Turnover, Proliferation, and Survival in the Adult Dentate Gyrus , 2005, The Journal of Neuroscience.

[118]  Arthur F. Kramer,et al.  BDNF mediates improvements in executive function following a 1-year exercise intervention , 2014, Front. Hum. Neurosci..

[119]  B. McEwen,et al.  Variant BDNF ( Val 66 Met ) polymorphism contributes to developmental and estrous-stage-specific expression of anxiety-like behavior in female mice , 2012 .

[120]  T. Bonhoeffer,et al.  The p75 Neurotrophin Receptor Negatively Modulates Dendrite Complexity and Spine Density in Hippocampal Neurons , 2005, The Journal of Neuroscience.

[121]  Barbara L. Hempstead,et al.  ProBDNF Induces Neuronal Apoptosis via Activation of a Receptor Complex of p75NTR and Sortilin , 2005, The Journal of Neuroscience.

[122]  E. Castrén,et al.  The antidepressant-like effects of glutamatergic drugs ketamine and AMPA receptor potentiator LY 451646 are preserved in bdnf +/− heterozygous null mice , 2012, Neuropharmacology.

[123]  Margit Burmeister,et al.  A BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression , 2003, Neuropsychopharmacology.

[124]  Jingyun Yang,et al.  No association of genetic variants in BDNF with major depression: A meta‐ and gene‐based analysis , 2013, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[125]  S. Cohen-Cory,et al.  Brain‐derived neurotrophic factor and the development of structural neuronal connectivity , 2010, Developmental neurobiology.

[126]  François-Laurent De Winter,et al.  Relationship Between Hippocampal Volume, Serum BDNF, and Depression Severity Following Electroconvulsive Therapy in Late-Life Depression , 2016, Neuropsychopharmacology.

[127]  K. Bath,et al.  Neurotrophic-priming of glucocorticoid receptor signaling is essential for neuronal plasticity to stress and antidepressant treatment , 2015, Proceedings of the National Academy of Sciences.

[128]  K. Bath,et al.  The BDNF Val66Met Polymorphism Impairs NMDA Receptor-Dependent Synaptic Plasticity in the Hippocampus , 2010, The Journal of Neuroscience.

[129]  Bernadette A. Thomas,et al.  Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 , 2012, The Lancet.

[130]  M. Bothwell NGF, BDNF, NT3, and NT4. , 2014, Handbook of experimental pharmacology.

[131]  M. Poo,et al.  Grand challenges in global mental health , 2011, Nature.

[132]  Yogesh K. Dwivedi,et al.  Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. , 2003, Archives of general psychiatry.

[133]  K. Hamazaki,et al.  Serum pro-BDNF/BDNF as a treatment biomarker for response to docosahexaenoic acid in traumatized people vulnerable to developing psychological distress: a randomized controlled trial , 2015, Translational Psychiatry.

[134]  Conor Liston,et al.  Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo , 2011, Proceedings of the National Academy of Sciences.

[135]  B. Penninx,et al.  Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484) , 2014, Molecular Psychiatry.

[136]  E. Castrén,et al.  Activation of the TrkB Neurotrophin Receptor Is Induced by Antidepressant Drugs and Is Required for Antidepressant-Induced Behavioral Effects , 2003, The Journal of Neuroscience.

[137]  J. Siuciak,et al.  Antidepressant-Like Effect of Brain-derived Neurotrophic Factor (BDNF) , 1997, Pharmacology Biochemistry and Behavior.

[138]  R. Duman,et al.  Serum Brain-Derived Neurotrophic Factor, Depression, and Antidepressant Medications: Meta-Analyses and Implications , 2008, Biological Psychiatry.

[139]  M. E. Frizzo,et al.  Riluzole Stimulates BDNF Release from Human Platelets , 2015, BioMed research international.

[140]  G. Tseng,et al.  Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with Major Depression , 2011, Molecular Psychiatry.

[141]  Ruoyan Chen,et al.  Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain , 2003, Biological Psychiatry.

[142]  G. Glover,et al.  A Genetic Variant BDNF Polymorphism Alters Extinction Learning in Both Mouse and Human , 2010, Science.

[143]  R. Duman,et al.  Brain-Derived Neurotrophic Factor Produces Antidepressant Effects in Behavioral Models of Depression , 2002, The Journal of Neuroscience.

[144]  C. Stewart,et al.  Repeated ECS and fluoxetine administration have equivalent effects on hippocampal synaptic plasticity , 2000, Psychopharmacology.

[145]  M. Chao,et al.  Shaping neurons: Long and short range effects of mature and proBDNF signalling upon neuronal structure , 2014, Neuropharmacology.

[146]  A. Mørk,et al.  The effect of escitalopram, desipramine, electroconvulsive seizures and lithium on brain-derived neurotrophic factor mRNA and protein expression in the rat brain and the correlation to 5-HT and 5-HIAA levels , 2004, Brain Research.

[147]  Barbara L. Hempstead,et al.  Sortilin is essential for proNGF-induced neuronal cell death , 2004, Nature.

[148]  Pradeep J. Nathan,et al.  BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases , 2013, Nature Reviews Neuroscience.

[149]  M. Cuesta,et al.  [Neurobiology of depression]. , 2002, Anales del sistema sanitario de Navarra.

[150]  E. Castrén Neurotrophic effects of antidepressant drugs. , 2004, Current opinion in pharmacology.

[151]  Serge Nef,et al.  Brain-Derived Neurotrophic Factor Conditional Knockouts Show Gender Differences in Depression-Related Behaviors , 2007, Biological Psychiatry.

[152]  Edward E. Smith,et al.  The Impact of Aerobic Exercise on Brain-Derived Neurotrophic Factor and Neurocognition in Individuals With Schizophrenia: A Single-Blind, Randomized Clinical Trial. , 2015, Schizophrenia bulletin.

[153]  B. Hempstead Deciphering proneurotrophin actions. , 2014, Handbook of experimental pharmacology.

[154]  Juha E. A. Knuuttila,et al.  Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat , 2007, Neuroscience.

[155]  D. Ye,et al.  Meta-analysis of BDNF Val66Met polymorphism association with treatment response in patients with major depressive disorder , 2010, European Neuropsychopharmacology.

[156]  E. Castrén Neurotrophins and psychiatric disorders. , 2014, Handbook of experimental pharmacology.