Single-Nucleotide Polymorphisms in TrkB and Risk for Depression: Findings From the Women’s Interagency HIV Study

Abstract:Individuals infected with HIV type 1 are more likely than noninfected individuals to develop depression. HIV lowers brain-derived neurotrophic factor (BDNF), a neurotrophic factor whose receptors play a crucial role in the pathophysiology of depression. Therefore, we examined whether a single-nucleotide polymorphism in the BDNF gene (rs56164415) and related receptors TrkB (rs1212171) and p75NTR (rs2072446) were associated with depression in HIV-infected individuals. A total of 1365 HIV-positive and 371 HIV-negative female subjects were included. The distribution of alleles was analyzed independently in African Americans (non-Hispanic) and Caucasians (non-Hispanic). We have found that the absence of depressive symptoms in HIV-positive subjects is associated with a genetic variation of the TrkB but not with BDNF or p75NTR genes. This mutation explains 0.8% and 4.4% of the variability for the absence of depression in African Americans and Caucasians, respectively.

[1]  L. Zecca,et al.  Human Immunodeficiency Virus Type 1 Alters Brain-Derived Neurotrophic Factor Processing in Neurons , 2012, The Journal of Neuroscience.

[2]  P. Barker,et al.  Regulation of a Truncated Form of Tropomyosin-Related Kinase B (TrkB) by Hsa-miR-185* in Frontal Cortex of Suicide Completers , 2012, PloS one.

[3]  R. Duman,et al.  Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents , 2012, Trends in Neurosciences.

[4]  H. Kunugi,et al.  Support for association between the Ser205Leu polymorphism of p75NTR and major depressive disorder , 2011, Journal of Human Genetics.

[5]  M. Torrens,et al.  Psychiatric, Behavioural and Social Risk Factors for HIV Infection Among Female Drug Users , 2011, AIDS and Behavior.

[6]  Rochelle E Tractenberg,et al.  HIV-1 decreases the levels of neurotrophins in human lymphocytes , 2011, AIDS.

[7]  Y. Lecrubier,et al.  Brain-derived neurotrophic factor gene polymorphisms: influence on treatment response phenotypes of major depressive disorder , 2011, International clinical psychopharmacology.

[8]  C. Allgulander,et al.  HIV infection and psychiatric illness. , 2009, African journal of psychiatry.

[9]  C. Siao,et al.  Neuronal release of proBDNF , 2009, Nature Neuroscience.

[10]  D. Bartel MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[11]  Eric J. Nestler,et al.  The molecular neurobiology of depression , 2008, Nature.

[12]  M. Furey,et al.  Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression , 2008, Brain Structure and Function.

[13]  R. Post Role of BDNF in bipolar and unipolar disorder: clinical and theoretical implications. , 2007, Journal of psychiatric research.

[14]  A. Nath,et al.  Neurologic complications: Challenges to the diagnosis and management of HIV dementia , 2006 .

[15]  C. Ward,et al.  In Vivo Restoration of Physiological Levels of Truncated TrkB.T1 Receptor Rescues Neuronal Cell Death in a Trisomic Mouse Model , 2006, Neuron.

[16]  H. Myers,et al.  Components of Depression in HIV-1 Infection: Their Differential Relationship to Neurocognitive Performance , 2006, Journal of clinical and experimental neuropsychology.

[17]  M. Young,et al.  The Women's Interagency HIV Study: an Observational Cohort Brings Clinical Sciences to the Bench , 2005, Clinical Diagnostic Laboratory Immunology.

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

[19]  E. Acquas,et al.  Human immunodeficiency virus type 1 glycoprotein gp120 reduces the levels of brain‐derived neurotrophic factor in vivo: potential implication for neuronal cell death , 2004, The European journal of neuroscience.

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

[21]  M. Chao,et al.  Neurotrophins and their receptors: A convergence point for many signalling pathways , 2003, Nature Reviews Neuroscience.

[22]  C. Cotman,et al.  Exercise: a behavioral intervention to enhance brain health and plasticity , 2002, Trends in Neurosciences.

[23]  T. Ten Have,et al.  Depressive and anxiety disorders in women with HIV infection. , 2002, The American journal of psychiatry.

[24]  J. Aubry,et al.  Decreased serum brain-derived neurotrophic factor levels in major depressed patients , 2002, Psychiatry Research.

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

[26]  D. Vlahov,et al.  Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study. , 2001, JAMA.

[27]  M. Cargill Characterization of single-nucleotide polymorphisms in coding regions of human genes , 1999, Nature Genetics.

[28]  J. Rabkin,et al.  The Relationship of Mood, Endocrine, and Sexual Disorders in Human Immunodeficiency Virus Positive (HIV+) Women: An Exploratory Study , 1998, Psychosomatic medicine.

[29]  S. Okazaki,et al.  CES-D scale , 2006 .