Bi-phasic change in BDNF gene expression following antidepressant drug treatment

Coppell, Alex; Pei, Qi; Zetterström, T.

doi:10.1016/s0028-3908(03)00077-7

Cited by 228 publications

(161 citation statements)

References 27 publications

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“…The involvement of BDNF in SB is supported by several studies showing a decreased level of BDNF in the hippocampus and prefrontal cortex (PFC) of suicide victims and in the cerebrospinal fluid (CSF) and plasma of suicide attempters (Dwivedi et al, 2003b;Karege et al, 2005;Kim et al, 2007). Although chronic antidepressant treatment has been shown to increase central expression of BDNF (Altar et al, 2003;Coppell et al, 2003), it has also been postulated that acute treatment could temporarily reduce BDNF transcripts (Dias et al, 2003). Decreased BDNF levels have been reported in the plasma and CSF of subjects with SB, so that it could be postulated that SB would be most pronounced in the acute phase of treatment.…”

Section: Discussionmentioning

confidence: 99%

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project

Perroud

Aitchison

Uher

et al. 2009

Neuropsychopharmacol

104

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The aim of this study was to investigate genetic predictors of an increase in suicidal ideation during treatment with a selective serotonin reuptake inhibitor or a tricyclic antidepressant. A total of 796 adult patients with major depressive disorder who were treated with a flexible dosage of escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP) were included in the sample and provided data on suicidal ideation. Nine candidate genes involved in neurotrophic, serotonergic, and noradrenergic pathways were selected based on previous association studies with suicidal ideation or behavior. Using a logistic regression model, 123 polymorphisms in these genes were compared between subjects with an increase in suicidal ideation and those without any increase in suicidal ideation. Polymorphisms in BDNF, the gene encoding the brain-derived neurotrophic factor, were significantly associated with an increase in suicidal ideation. The strongest association was observed for rs962369 in BDNF (p ¼ 0.0015). Moreover, a significant interaction was found between variants in BDNF and NTRK2, the gene encoding the BNDF receptor (p ¼ 0.0003). Among men taking nortriptyline, suicidality was also associated with rs11195419 SNP in the alpha 2A -adrenergic receptor gene (ADRA2A) (p ¼ 0.007). The associations observed with polymorphisms in BDNF suggest the involvement of the neurotrophic system in vulnerability to suicidality. Epistasis between BDNF and NTRK2 suggests that genetic variations in the two genes are involved in the same causal mechanisms leading to suicidality during antidepressant treatment. Among men, genetic variation in noradrenergic signaling may interact with norepinephrine reuptake-inhibiting antidepressants, thereby contributing to suicidality.

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Section: Discussionmentioning

confidence: 99%

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project

Perroud

Aitchison

Uher

et al. 2009

Neuropsychopharmacol

104

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“…Intracerebral ventricular or intrahippocampal administration of BDNF has been shown to have an antidepressant-like effect in various animal tests of antidepressant activity (Siuciak et al, 1997;Shirayama et al, 2002;Hoshaw et al, 2005). Furthermore, antidepressant medications have been shown to increase BDNF levels in the hippocampus (Nibuya et al, 1995;De Foubert et al, 2004;Russo-Neustadt et al, 2004; but see Altar et al, 2003;Coppell et al, 2003;Jacobsen and Mork, 2004). Further evidence for a role of BDNF in antidepressant action comes from studies using genetically modified mice with impaired levels of BDNF or its receptor TRK-B, which are resistant to the behavioral effects of antidepressants (Saarelainen et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Dysregulation of the HPA Axis and Increases Hippocampal BDNF Protein Levels: Implications for Stress-Related Psychiatric Disorders

Mitsukawa

Mombereau

Lötscher

et al. 2005

Neuropsychopharmacol

125

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Regulation of neurotransmission via group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) has recently been implicated in the pathophysiology of affective disorders, such as major depression and anxiety. For instance, mice with a targeted deletion of the gene for mGluR7 (mGluR7 À/À ) showed antidepressant and anxiolytic-like effects in a variety of stress-related paradigms, including the forced swim stress and the stress-induced hyperthermia tests. Deletion of mGluR7 reduces also amygdala-and hippocampus-dependent conditioned fear and aversion responses. Since the hypothalamic-pituitary-adrenal (HPA) axis regulates the stress response we investigate whether parameters of the HPA axis at the levels of selected mRNA transcripts and endocrine hormones are altered in mGluR7-deficient mice. Over all, mGluR7 À/À mice showed only moderately lower serum levels of corticosterone and ACTH compared with mGluR7 + / + mice. More strikingly however, we found strong evidence for upregulated glucocorticoid receptor (GR)-dependent feedback suppression of the HPA axis in mice with mGluR7 deficiency: (i) mRNA transcripts of GR were significantly upregulated in the hippocampus of mGluR7 À/À animals, (ii) similar increases were seen with 5-HT 1A receptor transcripts, which are thought to be directly controlled by the transcription factor GR and finally (iii) mGluR7 À/À mice showed elevated sensitivity to dexamethasone-induced suppression of serum corticosterone when compared with mGluR7 + / + animals. These results indicate that mGluR7 deficiency causes dysregulation of HPA axis parameters, which may account, at least in part, for the phenotype of mGluR7 À/À mice in animal models for anxiety and depression. In addition, we present evidence that protein levels of brain-derived neurotrophic factor are also elevated in the hippocampus of mGluR7 À/À mice, which we discuss in the context of the antidepressant-like phenotype found in those animals. We conclude that genetic ablation of mGluR7 in mice interferes at multiple sites in the neuronal circuitry and molecular pathways implicated in affective disorders.

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“…These stress effects have been suggested to be related to the development of depression and might be antagonized by application of various antidepressants. As mentioned above, it has been repeatedly shown that several antidepressants increase BDNF in rodents and humans (see Duman and Monteggia 2006; but also see Coppell et al 2003). In addition, intrahippocampal application of BDNF, but also NT-3, has been shown to have antidepressant-like effects on rats in the FST and learned helplessness paradigm (Shirayama et al 2002).…”

Section: Paroxetine-induced Effects On Neurotrophic Factorsmentioning

confidence: 90%

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

et al. 2008

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Introduction Monoamine-based antidepressants inhibit neurotransmitter reuptake within short time. However, it commonly takes several weeks until clinical symptoms start to resolve-indicating the involvement of effects distant from reuptake inhibition. Objective To unravel other mechanisms involved in drug action, a "reverse" pharmacological approach was applied to determine antidepressant-induced alterations of hippocampal gene expression. Materials and methodsThe behavioral response to longterm paroxetine administration of male DBA/2Ola mice was assessed by the forced swim test (FST), the modified hole board (mHB), and the dark/light box. Hippocampi of test-naive mice were dissected, and changes in gene expression by paroxetine treatment were investigated by means of microarray technology. Results and discussion Robust effects of paroxetine on passive stress-coping behavior in the FST were observed. Furthermore, anxiolytic properties of long-term antidepressant treatment could be identified in DBA mice in both, the mHB and dark/light box. Analysis of microarray results revealed a list of 60 genes differentially regulated by chronic paroxetine treatment. Preproenkephalin 1 and inhibin beta-A showed the highest level of transcriptional change. Furthermore, a number of candidates involved in neuroplasticity/neurogenesis emerged (e.g., Bdnf, Gfap, Vim, Sox11, Egr1, Stat3). Seven selected candidates were confirmed by in situ hybridization. Additional immunofluorescence colocalization studies of GFAP and vimentin showed more positive cells to be detected in long-term paroxetine-treated DBA mice. Conclusion Candidate genes identified in the current study using a mouse strain validated for its responsiveness to long-term paroxetine treatment add, in our opinion, to unraveling the mechanism of action of paroxetine as a representative for SSRIs.

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Bi-phasic change in BDNF gene expression following antidepressant drug treatment

Cited by 228 publications

References 27 publications

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project

Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Dysregulation of the HPA Axis and Increases Hippocampal BDNF Protein Levels: Implications for Stress-Related Psychiatric Disorders

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

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