Association of BDNF Serum Concentrations with Central Serotonergic Activity: Evidence from Auditory Signal Processing

Lang, Undine E.; Hellweg, Rainer; Gallinat, Jürgen

doi:10.1038/sj.npp.1300666

Cited by 41 publications

(27 citation statements)

References 60 publications

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“…Irrespective of the medication used, better treatment outcome was associated with higher BDNF plasma levels [143]. Moreover, BDNF polymorphism and serum level have been connected with anxiety, risk of depression, neuroticism and serotonergic neurotransmission [145,146,147,148,149]. Augmentation of antidepressants with lithium is currently the best-evidenced augmentation therapy in the treatment of depressed patients who do not respond to antidepressants [150] and also lithium augmentation leads to a BDNF increase [143].…”

Section: Depression As a Neurodegenerative Disordermentioning

confidence: 99%

Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies

Lang

Borgwardt²

2013

Cell Physiol Biochem

6,214

229

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Depression is a multicausal disorder and has been associated with the risk to develop cancer, dementia, diabetes, epilepsy and stroke. As a metabolic disorder depression has been associated with obesity, diabetes, insulin sensitivity, neuropeptide Y, glucose regulation, poor glycemic control, glucagone-like peptide-1, cholezystokinin, ghrelin, leptin, the endocannabinoid system, insulin-like growth factor and gastrin-releasing peptide. As a cardiovascular disease a close relationship exists between depression and blood pressure, heart rate, norepinephrine, sympathetic tone, vascular resistance, blood viscosity, plasma volume, intima thickness and atherosclerosis. Additionally blood coagulation, fibrinolysis, D-dimers, plasminogen activator inhibitor-1 protein, platelet activation, VEGF, plasma nitric oxide and its synthase are changed in depressed patients. As an endocrinological and stress disorder depression has been connected with the concentration of free T₄, TSH, CRH, arginine vasopressin, corticotrophin, corticosteroid release and ACTH. Depression as an inflammatory disorder is mediated by pro-inflammatory cytokines, interleukin-1, interleukin-6, TNF-alpha, soluble interleukin-2 receptors, interferon-alpha, interleukin 8, interleukin-10, hs-CRP, acute phase proteins, haptoglobin, toll like receptor 4, interleukin-1beta, mammalian target of rapamycin pathway, substance P, cyclooxygenase-2, prostaglandin-E2, lipid peroxidation levels and acid sphingomyelinase. Nutritional factors might influence depression risk, i.e. the consumption of folate, omega-3 fatty acids, monounsaturated fatty acids, olive oil, fish, fruits, vegetables, nuts, legumes, vitamin B6 and vitamin B12. The neurodegenerative hypothesis of depression explains decreased hippocampal volumes in depressed patients and changes of neurotrophic support by BDNF, erythropoietin, GDNF, FGF-2, NT3, NGF and growth hormone. In this context, a fast neuroprotective and antidepressant effect has also been observed by ketamine, which acts via the glutamatergic system. Hence, GABA, AMPA, EAAT, NMDA- and metabotropic glutamate receptors (mGluR1 to mGluR8) have gained interest in depression recently. Alternative, causative or also easy available treatment strategies beyond serotonin and noradrenaline reuptake inhibition might be a major topic of future psychiatric care. In this review, an attempt is made to overview concepts of the disease and search for perspectives on antidepressant treatment strategies beyond approved medications.

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Section: Depression As a Neurodegenerative Disordermentioning

confidence: 99%

Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies

Lang

Borgwardt²

2013

Cell Physiol Biochem

6,214

229

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“…PI3K signaling is triggered by a variety of growth factors including brain-derived neurotrophic factor (BDNF) [2,3], which has been implicated in bipolar disorder, depression, depression-related personality traits and anxiety [2,4,5,6,7]. Decreased expression of BDNF contributes to stress-related mood disorders and the upregulation of BDNF plays a role in the actions of different antidepressant treatments [8,9].…”

Section: Introductionmentioning

confidence: 99%

Akt2 Deficiency is Associated with Anxiety and Depressive Behavior in Mice

Leibrock

Ackermann

Hierlmeier

et al. 2013

Cell Physiol Biochem

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Background: The economic burden associated with major depressive disorder and anxiety disorders render both disorders the most common and debilitating psychiatric illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology, successful treatment and prevention of these highly associated disorders have not been identified. Akt2 is a key protein in the phosphatidylinositide-3 (PI3K) / glycogen synthase 3 kinase (GSK3) signaling pathway, which in turn is involved in brain-derived neurotrophic factor (BDNF) effects on fear memory, mood stabilisation and action of several antidepressant drugs. The present study thus explored the impact of Akt2 on behaviour of mice. Methods: Behavioural studies (Open-Field, Light-Dark box, O-Maze, Forced Swimming Test, Emergence Test, Object Exploration Test, Morris Water Maze, Radial Maze) have been performed with Akt2 knockout mice (akt^-/-) and corresponding wild type mice (akt^+/+). Results: Anxiety and depressive behavior was significantly higher in akt^-/- than in akt^+/+ mice. The akt^-/- mice were cognitively unimpaired but displayed increased anxiety in several behavioral tests (O-Maze test, Light-Dark box, Open Field test). Moreover, akt^-/- mice spent more time floating in the Forced Swimming test, which is a classical feature of experimental depression. Conclusion: Akt2 might be a key factor in the pathophysiology of depression and anxiety.

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“…In summary, the relationship between the LDAEP and serotonergic neurotransmission, while promising, requires more direct validation. Given the lack of selectivity of both the LDAEP and BDNF for the serotonergic system, the findings of the Lang et al (2005) study need to be interpreted with caution.…”

mentioning

confidence: 99%

“…Sir Lang et al (2005) reported a negative association between serum brain-derived neurotrophic factor (BDNF) levels and central serotonergic neurotransmission as measured by the loudness dependence (LD) of the auditory-evoked potential (AEP). The authors suggest that low serum BDNF concentrations reflect low central serotonergic neurotransmission as indicated by the strong LD of the AEP.…”

mentioning

confidence: 99%

Is the Loudness Dependence of the Auditory Evoked Potential a Sensitive and Selective In Vivo Marker of Central Serotonergic Function?

Nathan

O’Neill

Croft

2005

Neuropsychopharmacol

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SirLang et al (2005) reported a negative association between serum brain-derived neurotrophic factor (BDNF) levels and central serotonergic neurotransmission as measured by the loudness dependence (LD) of the auditory-evoked potential (AEP). The authors suggest that low serum BDNF concentrations reflect low central serotonergic neurotransmission as indicated by the strong LD of the AEP. While these findings are interesting and may suggest a relationship between central serotonin neurotransmission and serum BDNF levels, they need to be viewed with caution for a number of reasons. First, the relationship between LD of the AEP (LDAEP) and serotonin function in humans is tenuous, with the most convincing evidence for a direct relationship coming from animal studies exploring the 5-HT 1A receptor system (Juckel et al, 1997), with no such studies conducted in humans. Second, the specificity of the LDAEP as a marker of serotonin neurotransmission is questionable. For example, dopamine metabolites in CSF and urine have been found to correlate with the intensity dependence of visual and auditory N1/P2 components (Von Knorring and Perris, 1981), and Juckel et al (1997) also found that the D 1 /D 2 agonist apomorphine decreased the intensity dependence in animals, and more recently, a study in patients with obsessive-compulsive disorder found a correlation between the LDAEP and striatal dopamine transporter (DAT) binding (Pogarell et al, 2004). Consequently, only a relative specificity can be expected with regard to the LDAEP and its relationship to functional aspects of the serotonergic system. It is apparent that further studies are required to clarify the direct role of serotonin and other neuromodulators on LDAEP before this measure could be considered an in vivo marker of central serotonergic system. Accordingly, we have recently demonstrated, for the first time, a direct relationship between enhanced serotonin neurotransmission and the LD of the AEP in humans (Simmons et al, 2003;Nathan et al, 2005). In these studies, we demonstrated that both acute and chronic serotonin enhancement (using the serotonin reuptake inhibitors, citalopram and sertraline) resulted in a reduction of the slope of the LD of the AEP.Finally, while there are interactions between BDNF and the serotonergic system, similar interactions have also been noted between BDNF and the dopaminergic system. For example, in vitro survival, differentiation and function of dopamine neurons have been shown to be promoted by BDNF (Beck et al, 1993;Spina et al, 1992;Hyman et al, 1994). Furthermore, dopamine and D 1 receptor agonists have been shown to increase BDNF mRNA and protein, indicating a potential role for dopamine in BDNF expression (Kuppers and Beyer, 2001).These findings, together with the demonstration of a relationship between the LDAEP and dopamine neurotransmission, suggest that the results of the study by Lang and colleagues may in part be influenced by the dopaminergic system.In summary, the relationship between the LDAEP and serotonergic neuro...

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Association of BDNF Serum Concentrations with Central Serotonergic Activity: Evidence from Auditory Signal Processing

Cited by 41 publications

References 60 publications

Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies

Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies

Akt2 Deficiency is Associated with Anxiety and Depressive Behavior in Mice

Is the Loudness Dependence of the Auditory Evoked Potential a Sensitive and Selective In Vivo Marker of Central Serotonergic Function?

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