Neuroplasticity and memory formation in major depressive disorder: An imaging genetics perspective on serotonin and BDNF

Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel Vienna, Austria.
Restorative neurology and neuroscience (Impact Factor: 2.49). 04/2013; 32(1). DOI: 10.3233/RNN-139005
Source: PubMed


A vast number of imaging studies have demonstrated the impact of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) on emotion and memory-related networks in the context of Major Depressive Disorder (MDD). Underlying molecular mechanisms that affect the functionality of these networks have been examined in detail in animals and corroborate imaging findings. The crucial role of 5-HT and BDNF signaling in the context of MDD is reflected in the etiologic models of MDD such as the monoamine or neuroplasticity hypothesis as well as in pharmacological models of antidepressant response. While antidepressant drug treatment has been primarily linked to the modulation of emotion-related networks, cognitive behavioral therapy has been implicated in a top-down control of limbic structures. Initially, a simple lack of monoamines or BDNF has been proposed as causal factor of MDD etiology. However, recent findings suggest a much more complex neurobiology emphasizing epistatic and epigenetic mechanisms responsible for structural and functional changes observed in emotion and memory-related brain regions of healthy subjects and MDD patients. In this review, which focuses on neuroimaging studies in the context of MDD, the authors will provide a comprehensive overview of these networks as well as on the specific role of 5-HT and BDNF in their development and function.

Download full-text


Available from: Lukas Pezawas, Apr 26, 2014

  • No preview · Article · Jul 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Drugs acting through 5-hydroxytryptamine (serotonin or 5-HT) systems modulate memory and its alterations, although the mechanisms involved are poorly understood. 5-HT drugs may present promnesic and/or antiamnesic (or even being amnesic) effects. Key questions regarding 5-HT markers include whether receptors directly or indirectly participate and/or contribute to the physiological and pharmacological basis of memory and its pathogenesis; hence, the major aim of this article was to examine recent advances in emergent targets of the 5-HT systems for memory formation and memory alterations. Recent reviews and findings are summarized, mainly in the context of the growing notion of memory deficits in brain disorders (e.g., posttraumatic stress disorder, mild cognitive impairment, consumption of drugs, poststroke cognitive dysfunctions, schizophrenia, Parkinson disease, and infection-induced memory impairments). Mainly, mammalian and (some) human data were the focus. At least agonists and antagonists for 5-HT1A/1B, 5-HT2A/2B/2C, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors as well as serotonin uptake inhibitors seem to have a promnesic and/or antiamnesic effect in different conditions and 5-HT markers seem to be associated to neural changes. Available evidence offers clues about the possibilities, but the exact mechanisms remain unclear. For instance, 5-HT transporter expression seems to be a reliable neural marker related to memory mechanisms and its alterations.
    Full-text · Article · Dec 2013 · Reviews in the neurosciences
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The goal of this study was to determine whether a reduction in brain-derived neurotrophic factor (BDNF) levels in female mice leads to dopaminergic system dysregulation. Through a series of in vivo brain microdialysis and slice voltammetry experiments, we discerned that female BDNF heterozygous (BDNF+/-) mice are hyperdopaminergic, similar to their male BDNF+/- counterparts. Zero-net flux microdialysis results showed that female BDNF+/- mice had increased striatal extracellular dopamine levels, while stimulated regional release by high potassium concentrations potentiated dopamine release through vesicular- mediated depolarization. Using the complementary technique of fast scan cyclic voltammetry, electrical stimulation evoked greater dopamine release in the female BDNF+/- mice, whereas dopamine uptake remained unchanged relative to that of female wildtype mice. Following psychostimulant methamphetamine administration, female BDNF+/- mice showed potentiated dopamine release compared to their wildtype counterparts. Taken together, these dopamine release impairments in female mice appear to result in a hyperdopaminergic phenotype without concomitant alterations in dopamine uptake.
    Preview · Article · Feb 2014 · ACS Chemical Neuroscience
Show more