INT163479

Context Info Confidence 0.48 First Reported 2008 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 36 Total Number 36 Disease Relevance 25.77 Pain Relevance 14.83

extracellular region (Bdnf) cytoplasmic membrane-bounded vesicle (Bdnf)

Anatomy Link Frequency brain 2 dorsal 1 retina 1 cerebral cortex 1 tail 1 Bdnf (Mus musculus) Bdnf - V66M (5)

Pain Link Frequency Relevance Heat antidepressant 1865 100.00 Pain 137 100.00 bDMF 131 100.00 Nerve growth factor 113 100.00 Serotonin 104 100.00 midbrain 45 99.98 depression 1229 99.84 cerebral cortex 14 99.76 Inflammation 58 99.58 Chronic low back pain 3 99.16

Disease Link Frequency Relevance Heat Pain 173 100.00 Apoptosis 84 100.00 Nociception 61 100.00 Depression 1931 99.84 Suicidal Behaviour 1353 99.84 INFLAMMATION 64 99.58 Ganglion Cysts 14 99.52 Death 82 99.40 Anxiety Disorder 82 98.88 Low Back Pain 5 98.84

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Real et al.36 tested the association between the BDNF gene and antidepressant treatment outcome in OCD and found an association between therapeutic response and two of eight BDNF tag SNPs (rs908867 and rs1491850).

BDNF Binding (association) of associated with antidepressant and anxiety disorder

1) Confidence 0.48 Published 2010 Journal Psychiatry Investigation Section Body Doc Link PMC3022309 Disease Relevance 1.12 Pain Relevance 0.51

For example, a study by Kaufman et al.59 revealed a significant three-way interaction between the BDNF Val66Met genotype, the 5-HTTLPR genotype, and maltreatment history in predicting MDD in children.

BDNF Binding (interaction) of associated with depression

2) Confidence 0.48 Published 2010 Journal Psychiatry Investigation Section Body Doc Link PMC3022309 Disease Relevance 0.60 Pain Relevance 0.33

Fourthly, it may be of interest to explore the interaction of BDNF and genes in serotonergic pathways in response to antidepressants.

BDNF Binding (interaction) of associated with antidepressant

3) Confidence 0.48 Published 2010 Journal Psychiatry Investigation Section Body Doc Link PMC3022309 Disease Relevance 0.31 Pain Relevance 0.39

The same group of investigators extended this study in postmortem samples of subjects who completed suicide and healthy controls.193 They did not find a significant association of BDNF Val/Met polymorphism with suicide.

BDNF Neg (not) Binding (association) of associated with suicidal behaviour

4) Confidence 0.48 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 1.21 Pain Relevance 0.04

The study also tested 10 markers in BDNF for association with the outcome of citalopram treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample (n=1,953), but no significant associations were found with any of the 10 BDNF markers.

BDNF Binding (association) of associated with depression

5) Confidence 0.42 Published 2010 Journal Psychiatry Investigation Section Body Doc Link PMC3022309 Disease Relevance 1.05 Pain Relevance 0.51

Similarly, Choi et al163 reported that the genotype, allele, and allele-carrier distributions for the Val66Met polymorphism did not differ significantly between patients with MDD and healthy controls; however, they showed that the Val66Met polymorphism of BDNF was associated with citalopram efficacy, with Met-allele carriers responding better to citalopram treatment.

BDNF (V66M) Binding (associated) of associated with depression

6) Confidence 0.41 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 0.59 Pain Relevance 0.34

Genetic studies also indicate an association of BDNF to suicidal behavior.

BDNF Binding (association) of associated with suicidal behaviour

7) Confidence 0.41 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 2.11 Pain Relevance 0.27

Hong and colleagues190 were the first to study an association of BDNF with suicide.

BDNF Binding (association) of associated with suicidal behaviour

8) Confidence 0.41 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 0.98 Pain Relevance 0.06

However, in a subsequent genetic study, we found an association between BDNF Val66Met polymorphism and geriatric depression, chiefly in males.19 These findings are in line with a recent meta-analysis of 14 studies involving 2812 MDD cases and 10843 non-depressed controls, which revealed that the BDNF Val66Met polymorphism is not significantly associated with MDD; however, male gender and old age do have an impact on the association.20 PHARMACOGENETIC STUDY OF BDNF AND THERAPEUTIC RESPONSE TO ANTIDEPRESSANTS

BDNF (V66M) Binding (associated) of associated with depression

9) Confidence 0.37 Published 2010 Journal Psychiatry Investigation Section Body Doc Link PMC3022309 Disease Relevance 0.71 Pain Relevance 0.21

A positron emission tomography study has shown that male carriers of the Val/Val genotype of the BDNF Val66Met polymorphism display higher serotonin transporter density in the brain.58 Since both signaling systems have significant interactions with overlapping functional targets, it might be expected that they would have synergistic genetic effects on response to antidepressant treatment or MDD.

BDNF (V66M) Binding (interactions) of in brain associated with antidepressant, depression, positron emission tomography and serotonin

10) Confidence 0.37 Published 2010 Journal Psychiatry Investigation Section Body Doc Link PMC3022309 Disease Relevance 0.47 Pain Relevance 0.36

The</span> <span style="background-color:#FFFF00">BDNF rs7103411 and Val66Met polymorphisms were associated with treatment response over six weeks only in clinical subtypes of depression, such as melancholic depression (Val/Val <Met/Met, p=0.001).

BDNF (V66M) Binding (associated) of associated with depression

11) Confidence 0.37 Published 2010 Journal Psychiatry Investigation Section Body Doc Link PMC3022309 Disease Relevance 0.95 Pain Relevance 0.52

Future studies should consider genes in the BDNF signaling pathway, which may contribute or interact with BDNF in the response to antidepressant treatment.

BDNF Binding (interact) of associated with antidepressant

12) Confidence 0.36 Published 2010 Journal Psychiatry Investigation Section Body Doc Link PMC3022309 Disease Relevance 0.08 Pain Relevance 0.59

Using the TrkB inhibitor K-252a, or mice deficient for the common neurotrophin receptor p75(NTR), the regulation of GABAergic activity was shown specifically to be mediated by BDNF binding to the neurotrophin receptor TrkB.

BDNF Binding (binding) of associated with gabaergic

13) Confidence 0.35 Published 2009 Journal J. Neurosci. Section Abstract Doc Link 19812317 Disease Relevance 0 Pain Relevance 0.50

In human BDNF gene, there is a common functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF.

proBDNF Binding (trafficking) of

14) Confidence 0.33 Published 2010 Journal Psychiatry Investigation Section Abstract Doc Link PMC3022309 Disease Relevance 0.16 Pain Relevance 0.41

BDNF injected into the retina may be internalized by retinal ganglion neurons and transported to the SC, where BDNF may be released and transferred to the postsynaptic neurons [52].

BDNF Binding (internalized) of in retina associated with ganglion cysts

15) Confidence 0.32 Published 2009 Journal Molecular Vision Section Body Doc Link PMC2664844 Disease Relevance 0.30 Pain Relevance 0.03

Recent genetic studies also support a link of BDNF to depression/suicidal behavior.

BDNF Binding (link) of associated with suicidal behaviour and depression

16) Confidence 0.32 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Abstract Doc Link PMC2732010 Disease Relevance 1.01 Pain Relevance 0.30

Genetic studies linking BDNF to suicide

BDNF Binding (linking) of associated with suicidal behaviour

17) Confidence 0.32 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 1.09 Pain Relevance 0.09

Another piece of evidence demonstrating role of BDNF in depression comes from studies showing an association of personality traits and BDNF polymorphism.171–174 It is pertinent to mention that personality traits have been linked to major depression as well as suicide.175 Do epigenetics play any role in BDNF modification in depression and antidepressant responses?

BDNF Binding (association) of associated with antidepressant, suicidal behaviour and depression

18) Confidence 0.32 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 1.08 Pain Relevance 0.26

Similarly, intra-midbrain infusion of BDNF in rodents produces antidepressant-like effect in the forced swim test and learned helpless models of depression.134 Infusion of BDNF in the dorsal raphe nucleus also resulted in antidepressant-like effect in the learned helpless model of depression.136 Interestingly, the effects of BDNF on these behavioral paradigms were much longer lasting compared with classic antidepressants.135,137 Clinical studies of BDNF response in depressed patients before and after antidepressant treatment

BDNF Binding (infusion) of in dorsal associated with antidepressant, depression, eae, midbrain and raphe

19) Confidence 0.32 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 0.74 Pain Relevance 0.91

Because depression is an important causative factor in suicidal behavior, it is interesting to examine whether suicidal behavior is associated with alterations in BDNF and its cognate receptors.

BDNF Binding (alterations) of associated with suicidal behaviour and depression

20) Confidence 0.32 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 1.23 Pain Relevance 0.34

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