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BDNF (Brain-Derived Neurotrophic Factor) is not a hormone, but a protein and neurotrophin. It acts as a growth factor (neurotrophic factor) in the brain. Learning requires neurotrophic factors.
Stress reduces BDNF in the hippocampus.
BDNF influences brain development, synaptic plasticity, learning and memory as well as other neuronal processes. BDNF promotes the function of the hippocampus.
BDNF is involved in various disorders such as depression, schizophrenia, Alzheimer’s disease, dementia, Huntington’s disease, eating disorders, Rett syndrome and epilepsy.

Whether BDNF is altered in ADHD is unclear.
Stimulant treatment restores levels of BDNF and other neurotrophic factors, which improves the ability to learn (not only school or lecture material, but also meaningful changes in one’s behavior as a result of an experience). Endurance exercise also increases BDNF. Taurine increases BDNF in the striatum.
BDNF can be influenced by factors such as learning processes, antidepressants, physical activity, dietary restriction, light and sensory stimulation.
The effect of BDNF can be altered by stress, with chronic stress reducing BDNF levels in the hippocampus and increasing them in the nucleus accumbens.

There are different receptors for BDNF, including the TrkB receptor, which has a high affinity for BDNF, and the p75 receptor, which has a low affinity for BDNF.
BDNF can freely cross the blood-brain barrier.123 The BDNF blood serum level is said to correlate with the size of the hippocampus.4

1. Control areas of BDNF

1.1. Behavioral functions

BDNF controls many behavioral functions in cooperation with serotonin.

BDNF influenced:5

  • Brain development
  • neurogenesis
    • Differentiation of hippocampal neuron precursors6
  • Processes of neuronal plasticity
    • Direct
      • Cellular processes of neuronal plasticity
    • Indirect
      • Influence on other plasticity-modifying processes
    • Short term
      • Potentiation of synaptic excitation transmission through the depolarization of postsynaptic nerve cells
      • Facilitates the release of presynaptic neurotransmitters
    • Long-term
      • Persistent change in cell excitability and synaptic plasticity7
  • Activity-dependent synaptic plasticity86
    • synaptogenesis between Ia afferents and motor neurons6
  • memory consolidation9
    • The long-term potentiation (LTP) underlying learning and memory10
    • Deactivation of the BDNF gene or the BDNF receptor in mice
      • Restricts their learning behavior11 whereby the learning time required for spatial learning was doubled12
      • Impairs long-term potentiation, which is essential for long-term memory11
      • Prevents the improvement of learning through endurance training13
      • These effects can be remedied by an external supply of BDNF7
    • GABA inhibits long-term potentiation14
  • the sensitization of nociceptive fibres6
  • visceral sensory innervation, respiratory control6

BDNF promotes hippocampal function, in particular the survival of newly formed granule cells throughout adult life.15 BDNF modulates hippocampal plasticity and hippocampus-dependent memory.16

The transcription factor Cyclic AMP response element-binding protein (CREB1) is an important regulator of BDNF-induced gene expression. BDNF stimulates the phosphorylation and activation of CREB in nerve cells.17

BDNF influences the glutamate metabolism in the brain. In around 30 % of nerve cells, glutamatergic synaptic transmission is increased by 100 ng / ml each18

  • BDNF by 143 %
  • Neurotrophin-4/5 by 170 %

cAMP rapidly increases neurotrophin-3 (= BNDF-/NT-3 = tropomyosin receptor kinase B (TrkB) = tyrosine receptor kinase B) and causes BDNF-dependent long-term potentiation in the hippocampus.19

1.2. Disorders

BDNF is involved in various disorders, e.g.

  • Depression20
    • BDNF decreases in the hippocampus
    • BDNF increased in the nucleus accumbens21
    • BDNF decreases in blood plasma22
  • ADHD
    • Contradictory results, these below
  • Schizophrenia
  • Obsessive-compulsive disorder
  • Alzheimer’s20
    • BDNF reduces23
      • In the parietal cortex,24
      • In the hippocampus and temporal cortex25
      • In the entorhinal cortex26
    • NGF (Nerve Growth Factor) was higher in the dentate gyrus26
    • NT-3 was reduced in the motor cortex26
  • Dementia
  • Huntington’s disease
  • Eating disorders
    • Anorexia nervosa
    • Bulimia nervosa
  • Rett syndrome
  • Epilepsy

2. BDNF receptors

BDNF receptors are predominantly located in memory-relevant brain regions such as the PFC and hippocampus.8

2.1. TrkB receptor (TrkB)

The TrkB receptor has a high affinity for BDNF.8

2.2. Truncated TrkB receptor (TrkB-T)

2.3. P75 receptor

The p75 receptor has a low affinity for BDNF.8

3. Change in BDNF

3.1. Stress and BDNF

3.1.1. Stress reduces BDNF in the hippocampus

Stress reduces BDNF27 and BDNF expression in the hippocampus of humans and rats. Chronic administration of antidepressants prevents this.28

BDNF was significantly reduced by singular29 such as repeated immobilization in the hippocampus and dentate gyrus, but not neurotrophin-4 or tyrosine receptor kinases (trkB or C).
In contrast, NT-3 was increased in the hippocampus and dentate gyrus, but only during repeated immobilization (chronic stress), which was probably primarily mediated by corticosterone.
The reduction in BDNF occurred (only in the dentate gyrus) even without a corticosterone response (in rats that had had their adrenal cortex removed and were therefore unable to secrete corticosterone).30

The decrease in BDNF due to stress in the hippocampus and the increase in BDFN due to stress in the paraventricular hypothalamus may decrease with age, while the changes in NGF (Nerve Growth Factor) and neurotrophin-3 (NT-3) do not appear to change with age.31

One study found that BDNF was reduced by chronic glucocorticoid administration in the PFC, but not in the dorsal hippocampus.32

3.1.2. Chronic stress increases BDNF in the nucleus accumbens

Chronic stress increases BDNF expression in the nucleus accumbens, which in turn correlates with depression-like behaviors, such as early passivity33 or social phobia,34 but only in stress-prone, not stress-resistant rats.35

BDNF is also elevated in the nucleus accumbens in people with depression.21

Stress also has significant effects on BDNF in the amygdala and PFC.15

Blocking eye activity drastically reduces BDNF in the visual cortex of the affected eye.20

3.1.3. Chronic / acute stress and gender

In female rats, chronic stress decreased BDNF in prelimbic areas of the PFC, while acute stress increased BDNF in the dentate gyrus. In males, the values remained unchanged in both cases36
BDNF is also involved in the impairment of dopamine signaling during early childhood stress caused by maternal deprivation in rats.37

3.1.4. BDNF for DAT deficiency

DAT-KO mice that do not produce dopamine transporters show massive changes in BDNF in PFC and striatum:

  • In the PFC
    • Reduced BDNF gene expression38
    • Total BDNF and BDNF exon IV mRNA levels reduced39
    • MRNA levels of BDNF exon VI unchanged39
    • Reduced mBDNF levels and reduced trkB activation39
    • Reduced activation of αCaMKII in the PFC39
  • In the dorsolateral striatum
    • MBDNF level increased in the homogenate39
    • MBDNF levels in the cytosol increased39
    • MBDNF levels in the postsynaptic density are reduced.39
    • TrkB expression in the dorsolateral striatum postsynaptically reduced39
      • TrkB is a high-affinity BNDF receptor

3.2. Further changes to BDNF

BDNF is increased by27

  • Learning processes
  • Enriched environment / complex environments40
    • Varied, stimulating environments increase BDNF in rats
  • Antidepressants
  • Physical activity
    • Endurance sports significantly increase BDNF levels in the hippocampus and cerebral cortex.414243
    • Chronic estrogen deficiency of 7 weeks (but not acute estrogen deficiency of 3 weeks) reduces the increase of BDNF by endurance exercise in mice.44
  • Dietary restriction increases BDNF in the dentate gyrus45
  • Light and the circadian rhythm of daylight alter BDNF and neurotrophin-3.
    • In darkness, BDNF is high in the hippocampus (minimum 3.5 in light, maximum 17 in darkness)4647 in the cerebellum 48 and in the suprachiasmatic nucleus (SCN). In the SCN, BDNF levels were highest at dusk and dawn. In constant darkness, a BDNF rhythm was observed in the SCN, but not in the hippocampus.49
    • Light increases, darkness decreases BDNF in the visual cortex,50 the retina and superior colliculi48 as well as in the cerebral cortex. At least in the cerebral cortex, this rhythm is modulated by noradrenaline.51
  • Sensory stimulation of tactile hairs increases BDNF in the primary sensory cortex (barrel cortex).5253
  • Taurine significantly increased BDNF levels in the striatum in both SHR and WKY rats (whether low or high dose).54

4. Gene variants of BDNF

BDNF Val/Met correlated in humans, compared to BDNF Val/Val, with

  • A poorer episodic memory
  • Abnormal hippocampal activation on fMRI
  • Less N-acetyl-aspartate (NAA) in the hippocampus.16

5. BDNF and other growth factors and dopamine

5.1. BDNF regulates dopamine in the striatum

This presentation is based on Sulzer et al 55

The neurotrophic factor BDNF acts on TrkB (and P75) receptors.
Genetic elimination (BDNF-/- mice) or strong reduction of BDNF (BDNF-/+ mice) in the brain causes5657

  • evoked dopamine release
    • significantly reduced in the NAc shell
    • significantly reduced in the dorsal striatum
    • unchanged in the NAc core
  • dramatically increased consumption of high-fat food (intake of normal food unchanged)
  • normalized consumption of high-fat food due to D1 receptor agonists
  • extracellular dopamine levels in the caudate nucleus / putamen more than doubled
  • increased increase in dopamine levels after potassium stimulation (120 mM) (10-fold) compared to wild-type controls (6-fold)
  • electrically evoked dopamine release as well as the dopamine uptake rate in the caudate nucleus / putamen reduced

BDNF administration

  • increases the DA overflow in the striatum evoked by depolarization
  • can partially restore electrically evoked dopamine in BDNF-/+ mice
  • leaves extracellular dopamine levels unchanged

5.2. GDNF regulates dopamine release and dopamine uptake in the striatum

This presentation is based on Sulzer et al 55

The neurotrophic factor GDNF can regulate striatal DA release and uptake. GDNF plays a key role in the development, maintenance and regeneration of the mesostriatal DA system.58
In vivo, GDNF injection into the NAc caused an increase in K+-triggered DA release in the caudate nucleus/putamen59 via a long-lasting increase in TH phosphorylation and presumably DA synthesis in the striatum and SNc60
GDNF increases the amount of DA released from vesicles in axonal varicosities of midbrain DA neurons.61
GDNF increases the number of DA neurons in the midbrain and terminals in the striatum, thereby increasing dopamine in the striatum.62
GDNF regulates DAT surface expression via its receptor (Ret) by means of the guanine nucleotide exchange factor protein VAV2 (from the Rho family). Mice lacking Vav2 or Ret show increased DAT activity in the NAc.62

6. BDNF altered in ADHD?

The study situation on BDNF in ADHD is contradictory. No systematic change in BDNF in ADHD appears to be recognizable. There may be a gender-specific increase only in boys.


  • reduced (4 studies)4163
    • Reduced in the morning and evening for ADHD-HI and ADHD-C, reduced only in the evening for ADHD-I64
    • in adults with ADHD65
  • unchanged (3 studies)66
    • BDNF, NT-3, NGF and FGF-2 (fibroblast growth factor-2) unchanged in ADHD (blood serum).67
    • BDNF and NGF in blood serum unchanged, GDNF and NTF3 increased. No correlations between serum neurotrophin levels and ADHD severity.68
  • increased (3 studies, 1 meta-study)
    • in the blood serum, as well as NGF, GDNF, galanin.6970
    • in blood plasma71 with indications of a gender-dependent distribution
    • in the blood of male ADHD sufferers, unchanged in women72

Learning problems are typical in ADHD. Reduced BDNF in the hippocampus causes learning problems. In chronic stress, however, BDNF appears to be increased in the nucleus accumbens of stress-sensitive rats (see above).

Studies on the effect of ADHD medication on BDNF

In ADHD-HI and ADHD-C, BDNF appears to be reduced in the morning and evening, while in ADHD-I it is only reduced in the evening. MPH probably does not alter BDNF in ADHD-HI and ADHD-C, whereas MPH decreased BDNF in ADHD-I.64 An increase or decrease of BDNF by MPH could be age-dependent.7374
MPH reduced the previously elevated blood serum levels of BDNF, NGF, GDNF and galanin.69
MPH increased BDNF75 in the dorsal striatum only in male rats and in the nucleus accumbens regardless of sex.7677
Rats that received MPH as young animals had higher levels of BDNF in the PFC as they aged.78
Another study found that MPH caused a significant 42% decrease in BDNF in the striatum of female rats and a significant 50.4% increase in BDNF in the striatum of male rats. BDNF in the nucleus accumbens was unchanged.79
One study found no relevant effect of MPH on BDNF receptor expression in rats.80 Another study found that chronic MPH administration (1 to 3 mg/kg) increased BDNF mRNA expression in muscleblind-like 2 (Mbnl2) knockout mice.81 Another study found increased BDNF expression in the ventral tegmentum in adult rats after combined MPH/fluoxetine administration during adolescence.82

One study compared the effect of atomoxetine and methylphenidate on BDNF:83

  • Atomoxetine
    • increased BDNF mRNA levels
      • in the hippocampus
      • in the PFC
        • Total and exon IV BDNF mRNA levels increased
        • via increased AKT and GSK3β phosphorylation
  • Methylphenidate
    • increased BDNF gene expression
      • in the nucleus accumbens
      • in the Caudat putamen
    • reduced BDNF gene expression
      • in the PFC
      • via reduced synaptic levels of trkB, the high-affinity BDNF receptor, and reduced ERK1/2 activation

Atomoxetine reduced BDNF levels in adults with SDHD only in the ADHD-I group.84
In the dentate gyrus, only MPH, but not atomoxetine, appears to increase synaptic plasticity in rats, whereby a very high dose of 10 mg/kg body weight was used here. This is 5 to 15 times the usual dose of medication.85

As a result, the effect of MPH on BDNF seems to depend on the genetic circumstances, the time of MPH administration, age, gender and brain region.

The blood serum levels of VEGF (vascular endothelial growth factor) were significantly reduced in a study on ADHD, while those of GDNF (glial-derived neurotrophic factor) were significantly increased. However, their blood values did not correlate with the symptom severity of ADHD.67 Two studies found no altered blood serum levels of VEGF,8687 or IGF-1 or HIF-1α in children with ADHD.

In rats, MPH was associated with a significant increase in GDNF in the striatum and nucleus accumbens, irrespective of gender.76

The BDNF polymorphism Val66Met correlated with:88

  • reduced volume of gray matter in PFC and limbic structures89
  • altered connectivity of the default mode network in people with ADHD90

7. Epigenetic manipulation of BDNF by HDAC inhibitors

The universal HDAC inhibitor sulforaphane increased in vitro the levels of BDNF and components of the TrkB signaling cascade in mouse primary cortical neurons and in 3xTg-AD mice. The subsequent increase in acetylation of H3 and H4 in the vicinity of the P1 promoter of the BDNF gene led to increased levels of MAP 2 and the synaptic proteins synaptophysin and PSD-95. Sulforaphane thus appears to have an epigenetic effect on BDNF.91

BDNF is also involved in the impairment of dopamine signaling during early childhood stress induced by maternal deprivation in rats. Early infant maternal deprivation increased HDAC2 and decreased H3K9ac. Subsequent elevation of the dendritic spine modulator AKAP150 decreased synaptic levels of protein kinase A and increased mBDNF. These effects were reversed in vivo by a single administration of the HDAC inhibitor CI-994.37

  1. Sartorius, Hellweg, Litzke, Vogt, Dormann, Vollmay, Danker-Hopfe, Gass (2009): Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats. Pharmacopsychiatry. 2009 Nov;42(6):270-6. doi: 10.1055/s-0029-1224162. PMID: 19924587.

  2. Pan, Banks, Fasold, Bluth, Kastin (1998): Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology. 1998;37(12):1553-1561. doi:10.1016/s0028-3908(98)00141-5

  3. Poduslo, Curran (1996): Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF. Brain Res Mol Brain Res. 1996;36(2):280-286. doi:10.1016/0169-328x(95)00250-v

  4. IMD-Labor: BDNF – ein Serum-Marker bei Depression und Burnout

  5. Zarrouki (2012): Die Wirkung des BDNF-Polymorphismus auf transkraniell induzierte Neuroplastizität, Dissertation

  6. Huang EJ, Reichardt LF (2001): Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677-736. doi: 10.1146/annurev.neuro.24.1.677. PMID: 11520916; PMCID: PMC2758233. REVIEW

  7. Pearson-Fuhrhop, Kleim, Cramer (2009): Brain Plasticity and Genetic Factors, Topics in Stroke Rehabilitation, 16:4, 282-299, DOI: 10.1310/tsr1604-282

  8. Cunha, Brambilla, Thomas (2010): A simple role for BDNF in learning and memory? Front. Mol. Neurosci., 09 February 2010 |

  9. Figurov A, Pozzo-Miller LD, Olafsson P, Wang T, Lu B (1996): Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature. 1996 Jun 20;381(6584):706-9. doi: 10.1038/381706a0. PMID: 8649517.

  10. Laske, Eschweiler (2006) Brain-derived neurotrophic factor: Vom Nervenwachstumsfaktor zum Plastizitätsmodulator bei kognitiven Prozessen und psychischen Erkrankungen. Der Nervenarzt, May 2006, Volume 77, Issue 5, pp 523–537

  11. Korte (2001): Lernen und Gedächtnis: Zelluläre und molekulare Grundlagen, Biologie in unserer Zeit, 31: 296-304.<296::AID-BIUZ296>3.0.CO;2-C

  12. Linnarsson, Björklund, Ernfors (1997), Learning Deficit in BDNF Mutant Mice. European Journal of Neuroscience, 9: 2581-2587. doi:10.1111/j.1460-9568.1997.tb01687.x

  13. Vaynman, Gomez‐Pinilla (2006): Revenge of the “Sit”: How lifestyle impacts neuronal and cognitive health through molecular systems that interface energy metabolism with neuronal plasticity. Neurosci. Res., 84: 699-715.

  14. Dubrovsky: Reconsidering Classifi cations of Depression Syndromes: Lessons from Neuroactive Steroids and Evolutionary Sciences; in: Weizman (Herausgeber) (2008): Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment; Chapter 19, S 385 ff

  15. Feder, Nestler, Charney (2009): Psychobiology and molecular genetics of resilience. Nat Rev Neurosci. 2009 Jun; 10(6): 446–457. doi: 10.1038/nrn2649 PMC2833107. NIHMS174778 PMID: 19455174

  16. Egan, Kojima, Callicott, Goldberg, Kolachana, Bertolino, Zaitsev, Gold, Goldman, Dean, Lu, Weinberger (2003): The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003 Jan 24;112(2):257-69. doi: 10.1016/s0092-8674(03)00035-7. PMID: 12553913.

  17. Finkbeiner, Tavazoie, Maloratsky, Jacobs, Harris, Greenberg (1997): CREB: A Major Mediator of Neuronal Neurotrophin Responses, Neuron, Volume 19, Issue 5, 1997, Pages 1031-1047, ISSN 0896-6273,

  18. Leßmann, Heumann (1998): Modulation of unitary glutamatergic synapses by neurotrophin-4/5 or brain-derived neurotrophic factor in hippocampal microcultures: presynaptic enhancement depends on pre-established paired-pulse facilitation, Neuroscience, Volume 86, Issue 2, 1998, Pages 399-413, ISSN 0306-4522,

  19. Patterson, Pittenger, Morozov, Martin, Scanlin, Drake, Kandel (2001): Some Forms of cAMP-Mediated Long-Lasting Potentiation Are Associated with Release of BDNF and Nuclear Translocation of Phospho-MAP Kinase, Neuron, Volume 32, Issue 1, 2001, Pages 123-140, ISSN 0896-6273,

  20. Lu (2003): BDNF and activity-dependent synaptic modulation. Learn Mem. 2003 Mar-Apr;10(2):86-98.

  21. Krishnan, Han, Graham, Berton, Renthal, Russo, Laplant, Graham, Lutter, Lagace, Ghose, Reister, Tannous, Green, Neve, Chakravarty, Kumar, Eisch, Self, Lee, Tamminga, Cooper, Gershenfeld, Nestler (2007): Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell. 2007 Oct 19;131(2):391-404.

  22. Lee BH, Kim H, Park SH, Kim YK (2007): Decreased plasma BDNF level in depressive patients. J Affect Disord. 2007 Aug;101(1-3):239-44. doi: 10.1016/j.jad.2006.11.005. Epub 2006 Dec 13. PMID: 17173978. n = 172

  23. Hock C, Heese K, Hulette C, Rosenberg C, Otten U. Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol. 2000 Jun;57(6):846-51. doi: 10.1001/archneur.57.6.846. PMID: 10867782.

  24. Holsinger, Schnarr, Henry, Castelo, Fahnestock (2000): Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer’s disease. Brain Res Mol Brain Res. 2000 Mar 29;76(2):347-54.

  25. Connor, Young, Yan, Faull, Synek, Dragunow (1997): Brain-derived neurotrophic factor is reduced in Alzheimer’s disease. Brain Res Mol Brain Res. 1997 Oct 3;49(1-2):71-81.

  26. Narisawa-Saito, Wakabayashi, Tsuji, Takahashi, Nawa (1996): Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer’s disease. Neuroreport. 1996 Nov 25;7(18):2925-8.

  27. Zarrouki (2012): Die Wirkung des BDNF-Polymorphismus auf transkraniell induzierte Neuroplastizität, Dissertation

  28. Duman, Monteggia (2006): A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006 Jun 15;59(12):1116-27.

  29. Ueyama, Kawai, Nemoto, Sekimoto, Toné, Senba (1997): Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain. eurosci Res. 1997 Jun;28(2):103-10.

  30. Smith, Makino, Kvetnansky, Post (1995): Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci. 1995 Mar;15(3 Pt 1):1768-77.

  31. Smith, Cizza (1996): Stress-induced changes in brain-derived neurotrophic factor expression are attenuated in aged Fischer 344/N rats. Neurobiol Aging. 1996 Nov-Dec;17(6):859-64.

  32. Gourley, Kedves, Olausson, Taylor (2009): A history of corticosterone exposure regulates fear extinction and cortical NR2B, GluR2/3, and BDNF. Neuropsychopharmacology. 2009 Feb;34(3):707-16. doi: 10.1038/npp.2008.123.

  33. Eisch, Bolaños, de Wit, Simonak, Pudiak, Barrot, Verhaagen, Nestler (2003): Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression. Biol Psychiatry. 2003 Nov 15;54(10):994-1005.

  34. Berton, McClung, Dileone, Krishnan, Renthal, Russo, Graham, Tsankova, Bolanos, Rios, Monteggia, Self, Nestler (2006): Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science. 2006 Feb 10;311(5762):864-8.

  35. Krishnan, Han, Graham, Berton, Renthal, Russo, Laplant, Graham, Lutter, Lagace, Ghose, Reister, Tannous, Green, Neve, Chakravarty, Kumar, Eisch, Self, Lee, Tamminga, Cooper, Gershenfeld, Nestler (2007): Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell. 2007 Oct 19;131(2):391-404.

  36. Lin, Ter Horst, Wichmann, Bakker, Liu, Li, Westenbroek (2009): Sex differences in the effects of acute and chronic stress and recovery after long-term stress on stress-related brain regions of rats. Cereb Cortex. 2009 Sep;19(9):1978-89. doi: 10.1093/cercor/bhn225.

  37. Shepard RD, Gouty S, Kassis H, Berenji A, Zhu W, Cox BM, Nugent FS (2018): Targeting histone deacetylation for recovery of maternal deprivation-induced changes in BDNF and AKAP150 expression in the VTA. Exp Neurol. 2018 Nov;309:160-168. doi: 10.1016/j.expneurol.2018.08.002. PMID: 30102916; PMCID: PMC6139260.

  38. Fumagalli, Racagni, Colombo, Riva (2003): BDNF gene expression is reduced in the frontal cortex of dopamine transporter knockout mice. Mol Psychiatry. 2003 Nov;8(11):898-9. doi: 10.1038/ PMID: 14593425.

  39. Leo, Sukhanov, Zoratto, Illiano, Caffino, Sanna, Messa, Emanuele, Esposito, Dorofeikova, Budygin, Mus, Efimova, Niello, Espinoza, Sotnikova, Hoener, Laviola, Fumagalli, Adriani, Gainetdinov (2018): Pronounced Hyperactivity, Cognitive Dysfunctions, and BDNF Dysregulation in Dopamine Transporter Knock-out Rats. J Neurosci. 2018 Feb 21;38(8):1959-1972. doi: 10.1523/JNEUROSCI.1931-17.2018. PMID: 29348190; PMCID: PMC5824739.

  40. Spires, Grote, Varshney, Cordery, van Dellen, Blakemore, Hannan (2004): Environmental enrichment rescues protein deficits in a mouse model of Huntington’s disease, indicating a possible disease mechanism. J Neurosci. 2004 Mar 3;24(9):2270-6.

  41. Archer, Kostrzewa (2012): Physical exercise alleviates ADHD symptoms: regional deficits and development trajectory. Neurotox Res. 2012 Feb;21(2):195-209. doi: 10.1007/s12640-011-9260-0.

  42. Neeper, Gómez-Pinilla, Choi, Cotman (1996): Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 1996 Jul 8;726(1-2):49-56.

  43. Oliff, Berchtold, Isackson, Cotman (1998): Exercise-induced regulation of brain-derived neurotrophic factor (BDNF) transcripts in the rat hippocampus. Brain Res Mol Brain Res. 1998 Oct 30;61(1-2):147-53.

  44. Berchtold, Kesslak, Pike, Adlard, Cotman (2001): Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus. Eur J Neurosci. 2001 Dec;14(12):1992-2002.

  45. Lee, Duan, Long, Ingram, Mattson (2000): Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. J Mol Neurosci. 2000 Oct;15(2):99-108.

  46. Bova, Micheli, Qualadrucci, Zucconi (1989): BDNF and trkB mRNAs oscillate in rat brain during the light-dark cycle. Brain Res Mol Brain Res. 1998 Jun 15;57(2):321-4.

  47. Berchtold, Oliff, Isackson, Cotman (1999): Hippocampal BDNF mRNA shows a diurnal regulation, primarily in the exon III transcript. Brain Res Mol Brain Res. 1999 Jul 23;71(1):11-22.

  48. Pollock, Vernon, Forbes, Yan, Ma, Hsieh, Robichon, Frost, Johnson (2001): Effects of early visual experience and diurnal rhythms on BDNF mRNA and protein levels in the visual system, hippocampus, and cerebellum. J Neurosci. 2001 Jun 1;21(11):3923-31.

  49. Liang, Walline, Earnest (1998): Circadian rhythm of brain-derived neurotrophic factor in the rat suprachiasmatic nucleus. Neurosci Lett. 1998 Feb 13;242(2):89-92.

  50. Castrén, Zafra, Thoenen, Lindholm (1992): Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9444-8.

  51. Cirelli, Tononi (2000) Differential Expression of Plasticity-Related Genes in Waking and Sleep and Their Regulation by the Noradrenergic System. Journal of Neuroscience 15 December 2000, 20 (24) 9187-9194; DOI:

  52. Rocamora, Welker, Pascual, Soriano (1996): Upregulation of BDNF mRNA expression in the barrel cortex of adult mice after sensory stimulation. J Neurosci. 1996 Jul 15;16(14):4411-9.

  53. Nanda, Mack (2000): Seizures and sensory stimulation result in different patterns of brain derived neurotrophic factor protein expression in the barrel cortex and hippocampus. Brain Res Mol Brain Res. 2000 May 31;78(1-2):1-14.

  54. Chen, Chiu, Chen, Hsu, Tzang (2018): Effects of taurine on striatal dopamine transporter expression and dopamine uptake in SHR rats; Behav Brain Res. 2018 Apr 22. pii: S0166-4328(18)30306-1. doi: 10.1016/j.bbr.2018.04.031.

  55. Sulzer D, Cragg SJ, Rice ME (2016): Striatal dopamine neurotransmission: regulation of release and uptake. Basal Ganglia. 2016 Aug;6(3):123-148. doi: 10.1016/j.baga.2016.02.001. PMID: 27141430; PMCID: PMC4850498. REVIEW

  56. Cordeira JW, Frank L, Sena-Esteves M, Pothos EN, Rios M (2010): Brain-derived neurotrophic factor regulates hedonic feeding by acting on the mesolimbic dopamine system. J Neurosci. 2010 Feb 17;30(7):2533-41. doi: 10.1523/JNEUROSCI.5768-09.2010. PMID: 20164338; PMCID: PMC2846779.

  57. Bosse KE, Maina FK, Birbeck JA, France MM, Roberts JJ, Colombo ML, Mathews TA (2012): Aberrant striatal dopamine transmitter dynamics in brain-derived neurotrophic factor-deficient mice. J Neurochem. 2012 Feb;120(3):385-95. doi: 10.1111/j.1471-4159.2011.07531.x. PMID: 21988371; PMCID: PMC3385875.

  58. Kramer ER, Liss B (2015): GDNF-Ret signaling in midbrain dopaminergic neurons and its implication for Parkinson disease. FEBS Lett. 2015 Dec 21;589(24 Pt A):3760-72. doi: 10.1016/j.febslet.2015.11.006. PMID: 26555190. REVIEW

  59. Gash DM, Zhang Z, Cass WA, Ovadia A, Simmerman L, Martin D, Russell D, Collins F, Hoffer BJ, Gerhardt GA (1995): Morphological and functional effects of intranigrally administered GDNF in normal rhesus monkeys. J Comp Neurol. 1995 Dec 18;363(3):345-58. doi: 10.1002/cne.903630302. PMID: 8847404.

  60. Salvatore MF, Zhang JL, Large DM, Wilson PE, Gash CR, Thomas TC, Haycock JW, Bing G, Stanford JA, Gash DM, Gerhardt GA (2004): Striatal GDNF administration increases tyrosine hydroxylase phosphorylation in the rat striatum and substantia nigra. J Neurochem. 2004 Jul;90(1):245-54. doi: 10.1111/j.1471-4159.2004.02496.x. PMID: 15198683.

  61. Pothos EN, Davila V, Sulzer D (1998): Presynaptic recording of quanta from midbrain dopamine neurons and modulation of the quantal size. J Neurosci. 1998 Jun 1;18(11):4106-18. doi: 10.1523/JNEUROSCI.18-11-04106.1998. PMID: 9592091; PMCID: PMC6792796.

  62. Sulzer D, Cragg SJ, Rice ME (2016): Striatal dopamine neurotransmission: regulation of release and uptake. Basal Ganglia. 2016 Aug;6(3):123-148. doi: 10.1016/j.baga.2016.02.001. PMID: 27141430; PMCID: PMC4850498. REVIEW

  63. Tsai SJ. Attention-deficit hyperactivity disorder may be associated with decreased central brain-derived neurotrophic factor activity: clinical and therapeutic implications. Med Hypotheses. 2007;68(4):896-9. doi: 10.1016/j.mehy.2006.06.025. PMID: 16919891.

  64. Cubero-Millán, Ruiz-Ramos, Molina-Carballo, Martínez-Serrano, Fernández-López, Machado-Casas, Tortosa-Pinto, Ruiz-López, Luna-Del-Castillo, Uberos, Muñoz-Hoyos (2016): BDNF concentrations and daily fluctuations differ among ADHD children and respond differently to methylphenidate with no relationship with depressive symptomatology. Psychopharmacology (Berl). 2017 Jan;234(2):267-279. doi: 10.1007/s00213-016-4460-1.

  65. Corominas-Roso M, Ramos-Quiroga JA, Ribases M, Sanchez-Mora C, Palomar G, Valero S, Bosch R, Casas M (2013): Decreased serum levels of brain-derived neurotrophic factor in adults with attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol. 2013 Jul;16(6):1267-1275. doi: 10.1017/S1461145712001629. PMID: 23363778. n = 113

  66. Scassellati C, Zanardini R, Tiberti A, Pezzani M, Valenti V, Effedri P, Filippini E, Conte S, Ottolini A, Gennarelli M, Bocchio-Chiavetto L (2014): Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit-hyperactivity disorder (ADHD). Eur Child Adolesc Psychiatry. 2014 Mar;23(3):173-7. doi: 10.1007/s00787-013-0447-1. PMID: 23812866. n = 90

  67. Yurteri, Şahin, Tufan (2019): Altered serum levels of vascular endothelial growth factor and glial-derived neurotrophic factor but not fibroblast growth factor-2 in treatment-naive children with attention deficit/hyperactivity disorder. Nord J Psychiatry. 2019 May – Jul;73(4-5):302-307. doi: 10.1080/08039488.2019.1625437.

  68. Bilgiç A, Toker A, Işık Ü, Kılınç İ (2017): Serum brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 levels in children with attention-deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry. 2017 Mar;26(3):355-363. doi: 10.1007/s00787-016-0898-2. PMID: 27561780. n = 154

  69. Gumus C, Yazici IP, Yazici KU, Ustundag B (2022): Increased Serum Brain-derived Neurotrophic Factor, Nerve Growth Factor, Glial-derived Neurotrophic Factor and Galanin Levels in Children with Attention Deficit Hyperactivity Disorder, and the Effect of 10 Weeks Methylphenidate Treatment. Clin Psychopharmacol Neurosci. 2022 Nov 30;20(4):635-648. doi: 10.9758/cpn.2022.20.4.635. PMID: 36263639; PMCID: PMC9606423. n = 118

  70. Shim SH, Hwangbo Y, Kwon YJ, Jeong HY, Lee BH, Lee HJ, Kim YK (2008): Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD). Prog Neuropsychopharmacol Biol Psychiatry. 2008 Dec 12;32(8):1824-8. doi: 10.1016/j.pnpbp.2008.08.005. n = 148

  71. Li H, Liu L, Tang Y, Ji N, Yang L, Qian Q, Wang Y (2014): Sex-specific association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and plasma BDNF with attention-deficit/hyperactivity disorder in a drug-naïve Han Chinese sample. Psychiatry Res. 2014 Jul 30;217(3):191-7. doi: 10.1016/j.psychres.2014.03.011. PMID: 24713358. n = 325

  72. Zhang J, Luo W, Li Q, Xu R, Wang Q, Huang Q (2018): Peripheral brain-derived neurotrophic factor in attention-deficit/hyperactivity disorder: A comprehensive systematic review and meta-analysis. J Affect Disord. 2018 Feb;227:298-304. doi: 10.1016/j.jad.2017.11.012. Epub 2017 Nov 6. PMID: 29132072. METASTUDY

  73. Andersen, Sonntag (2014): Juvenile methylphenidate reduces prefrontal cortex plasticity via D3 receptor and BDNF in adulthood. Front Synaptic Neurosci. 2014 Jan 21;6:1. doi: 10.3389/fnsyn.2014.00001. eCollection 2014.

  74. Wetzell, Muller, Cobuzzi, Hurwitz, DeCicco-Skinner, Riley (2014): Effect of age on methylphenidate-induced conditioned taste avoidance and related BDNF/TrkB signaling in the insular cortex of the rat. Psychopharmacology (Berl). 2014 Apr;231(8):1493-501. doi: 10.1007/s00213-014-3500-y.

  75. Amiri A, Torabi Parizi G, Kousha M, Saadat F, Modabbernia MJ, Najafi K, Atrkar Roushan Z (2013): Changes in plasma Brain-derived neurotrophic factor (BDNF) levels induced by methylphenidate in children with Attention deficit-hyperactivity disorder (ADHD). Prog Neuropsychopharmacol Biol Psychiatry. 2013 Dec 2;47:20-4. doi: 10.1016/j.pnpbp.2013.07.018. PMID: 23933054. n = 28

  76. Roeding, Perna, Cummins, Peterson, Palmatier, Brown (2014): Sex differences in adolescent methylphenidate sensitization: effects on glial cell-derived neurotrophic factor and brain-derived neurotrophic factor. Behav Brain Res. 2014 Oct 15;273:139-43. doi: 10.1016/j.bbr.2014.07.014.

  77. Fumagalli, Cattaneo, Caffino, Ibba, Racagni, Carboni, Gennarelli, Riva (2010): Sub-chronic exposure to atomoxetine up-regulates BDNF expression and signalling in the brain of adolescent spontaneously hypertensive rats: comparison with methylphenidate. Pharmacol Res. 2010 Dec;62(6):523-9. doi: 10.1016/j.phrs.2010.07.009.

  78. Simchon Tenenbaum, Weizman, Rehavi (2015): The Impact of Chronic Early Administration of Psychostimulants on Brain Expression of BDNF and Other Neuroplasticity-Relevant Proteins. J Mol Neurosci. 2015 Oct;57(2):231-42. doi: 10.1007/s12031-015-0611-9.

  79. Brown, Hughes, Hughes, Sheppard, Perna, Ragsdale, Roeding, Pond (2012): Sex and dose-related differences in methylphenidate adolescent locomotor sensitization and effects on brain-derived neurotrophic factor. J Psychopharmacol. 2012 Nov;26(11):1480-8. doi: 10.1177/0269881112454227.

  80. Chase, Carrey, Soo, Wilkinson (2006): Methylphenidate regulates activity regulated cytoskeletal associated but not brain-derived neurotrophic factor gene expression in the developing rat striatum. Neuroscience. 2007 Feb 9;144(3):969-84.

  81. Ramon-Duaso, Gener, Consegal, Fernández-Avilés, Gallego, Castarlenas, Swanson, de la Torre, Maldonado, Puig, Robledo (2019): Methylphenidate Attenuates the Cognitive and Mood Alterations Observed in Mbnl2 Knockout Mice and Reduces Microglia Overexpression. Cereb Cortex. 2019 Jul 5;29(7):2978-2997. doi: 10.1093/cercor/bhy164.

  82. Warren, Iñiguez, Alcantara, Wright, Parise, Weakley, Bolaños-Guzmán (2011): Juvenile administration of concomitant methylphenidate and fluoxetine alters behavioral reactivity to reward- and mood-related stimuli and disrupts ventral tegmental area gene expression in adulthood. J Neurosci. 2011 Jul 13;31(28):10347-58. doi: 10.1523/JNEUROSCI.1470-11.2011.

  83. Fumagalli F, Cattaneo A, Caffino L, Ibba M, Racagni G, Carboni E, Gennarelli M, Riva MA (2010): Sub-chronic exposure to atomoxetine up-regulates BDNF expression and signalling in the brain of adolescent spontaneously hypertensive rats: comparison with methylphenidate. Pharmacol Res. 2010 Dec;62(6):523-9. doi: 10.1016/j.phrs.2010.07.009. PMID: 20691787.

  84. Ramos-Quiroga JA, Corominas-Roso M, Palomar G, Gomez-Barros N, Ribases M, Sanchez-Mora C, Bosch R, Nogueira M, Corrales M, Valero S, Casas M. Changes in the serum levels of brain-derived neurotrophic factor in adults with attention deficit hyperactivity disorder after treatment with atomoxetine. Psychopharmacology (Berl). 2014 Apr;231(7):1389-95. doi: 10.1007/s00213-013-3343-y. PMID: 24202115. n = 35

  85. Lee, Lee, Kim, Yan, Park, Kwon, Park, Ahn, Cho, Won, Kim (2012): Effects of ADHD therapeutic agents, methylphenidate and atomoxetine, on hippocampal neurogenesis in the adolescent mouse dentate gyrus. Neurosci Lett. 2012 Aug 30;524(2):84-8. doi: 10.1016/j.neulet.2012.07.029.

  86. Torun, Güney, Aral, Büyüktaşkin, Tunca, Taner, İşeri (2019): Determination of Serum Vascular Endothelial Growth Factor Levels in Attention Deficit Hyperactivity Disorder: A Case Control Study. Clin Psychopharmacol Neurosci. 2019 Nov 20;17(4):517-522. doi: 10.9758/cpn.2019.17.4.517. n = 87

  87. Ertürk E, Işık Ü, Şirin FB. Analysis of Serum VEGF, IGF-1, and HIF-1α Levels in ADHD. J Atten Disord. 2023 Sep 13:10870547231197211. doi: 10.1177/10870547231197211. PMID: 37700676. n = 80

  88. Huang W, Fateh AA, Zhao Y, Zeng H, Yang B, Fang D, Zhang L, Meng X, Hassan M, Wen F (2023): Effects of the SNAP-25 Mnll variant on hippocampal functional connectivity in children with attention deficit/hyperactivity disorder. Front Hum Neurosci. 2023 Aug 10;17:1219189. doi: 10.3389/fnhum.2023.1219189. PMID: 37635807; PMCID: PMC10447972.

  89. Gerritsen L, Tendolkar I, Franke B, Vasquez AA, Kooijman S, Buitelaar J, Fernández G, Rijpkema M (2012): BDNF Val66Met genotype modulates the effect of childhood adversity on subgenual anterior cingulate cortex volume in healthy subjects. Mol Psychiatry. 2012 Jun;17(6):597-603. doi: 10.1038/mp.2011.51. PMID: 21577214.

  90. Woelfer M, Li M, Colic L, Liebe T, Di X, Biswal B, Murrough J, Lessmann V, Brigadski T, Walter M (2020): Ketamine-induced changes in plasma brain-derived neurotrophic factor (BDNF) levels are associated with the resting-state functional connectivity of the prefrontal cortex. World J Biol Psychiatry. 2020 Nov;21(9):696-710. doi: 10.1080/15622975.2019.1679391. PMID: 31680600. RCT

  91. Kim J, Lee S, Choi BR, Yang H, Hwang Y, Park JH, LaFerla FM, Han JS, Lee KW, Kim J (2017): Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways. Mol Nutr Food Res. 2017 Feb;61(2). doi: 10.1002/mnfr.201600194. PMID: 27735126.