Are BDNF and Stress Levels Related to Antidepressant Response?
Abstract
1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Participants
4.2. Design
4.3. Evaluations
4.3.1. Sociodemographic and Clinical Characteristics
4.3.2. AMAI
4.3.3. HDRS
4.3.4. STAI-S
4.3.5. Procedures
4.3.6. Laboratory Test
4.3.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- World Health Organization (WHO). Yearbook of the United Nations 2005; United Nations: New York, NY, USA, 2005; pp. 1572–1573. [Google Scholar]
- Trivedi, M.H.; Rush, A.J.; Wisniewski, S.R.; Nierenberg, A.A.; Warden, D.; Ritz, L.; Norquist, G.; Howland, R.H.; Lebowitz, B.; McGrath, P.J.; et al. Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice. Am. J. Psychiatry 2006, 163, 28–40. [Google Scholar] [CrossRef] [PubMed]
- Rodríguez-Carrillo, A.; Verheyen, V.J.; Van Nuijs, A.L.N.; Fernández, M.F.; Remy, S. Brain-derived neurotrophic factor (BDNF): An effect biomarker of neurodevelopment in human biomonitoring programs. Front. Toxicol. 2023, 5, 1319788. [Google Scholar] [CrossRef] [PubMed]
- Zou, Y.; Zhang, Y.; Tu, M.; Ye, Y.; Li, M.; Ran, R.; Zou, Z. Brain-derived neurotrophic factor levels across psychiatric disorders: A systemic review and network meta-analysis. Prog. Neuropsychopharmacol. Biol. Psychiatry 2024, 131, 110954. [Google Scholar] [CrossRef] [PubMed]
- Sharma, V.; Singh, T.G.; Kaur, A.; Mannan, A.; Dhiman, S. Brain-Derived Neurotrophic Factor: A Novel Dynamically Regulated Therapeutic Modulator in Neurological Disorders. Neurochem. Res. 2023, 48, 317–339. [Google Scholar] [CrossRef]
- Fioranelli, M.; Garo, M.L.; Roccia, M.G.; Prizbelek, B.; Sconci, F.R. Brain-Heart Axis: Brain-Derived Neurotrophic Factor and Cardiovascular Disease-A Review of Systematic Reviews. Life 2023, 13, 2252. [Google Scholar] [CrossRef]
- Duman, R.S.; Deyama, S.; Fogaça, M.V. Role of BDNF in the pathophysiology and treatment of depression: Activity-dependent effects distinguish rapid-acting antidepressants. Eur. J. Neurosci. 2021, 53, 126–139. [Google Scholar] [CrossRef]
- Cavaleri, D.; Moretti, F.; Bartoccetti, A.; Mauro, S.; Crocamo, C.; Carrà, G.; Bartoli, F. The role of BDNF in major depressive disorder, related clinical features, and antidepressant treatment: Insight from meta-analyses. Neurosci Biobehav. Rev. 2023, 149, 105159. [Google Scholar] [CrossRef]
- Sagud, M.; Nikolac Perkovic, M.; Dvojkovic, A.; Jaksic, N.; Vuksan-Cusa, B.; Zivkovic, M.; Kusevic, Z.; Mihaljevic-Peles, A.; Pivac, N. Distinct association of plasma BDNF concentration and cognitive function in depressed patients treated with vortioxetine or escitalopram. Psychopharmacology 2021, 238, 1575–1584. [Google Scholar] [CrossRef]
- Matrisciano, F.; Bonaccorso, S.; Ricciardi, A.; Scaccianoce, S.; Panaccione, I.; Wang, L.; Ruberto, A.; Tatarelli, R.; Nicoletti, F.; Girardi, P.; et al. Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine. J. Psychiatr. Res. 2009, 43, 247–254. [Google Scholar] [CrossRef]
- Lee, Y.; Lim, S.W.; Kim, S.Y.; Chung, J.W.; Kim, J.; Myung, W.; Song, J.; Kim, S.; Carroll, B.J.; Kim, D.K. Association between the BDNF Val66Met Polymorphism and Chronicity of Depression. Psychiatry Investig. 2013, 10, 56–61. [Google Scholar] [CrossRef]
- Takebayashi, N.; Maeshima, H.; Baba, H.; Nakano, Y.; Satomura, E.; Kita, Y.; Namekawa, Y.; Nomoto, H.; Suzuki, T.; Arai, H. Duration of last depressive episode may influence serum BDNF levels in remitted patients with major depression. Depress. Anxiety 2012, 29, 775–779. [Google Scholar] [CrossRef] [PubMed]
- Chiba, S.; Numakawa, T.; Ninomiya, M.; Richards, M.C.; Wakabayashi, C.; Kunugi, H. Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Prog. Neuropsychopharmacol. Biol. Psychiatry 2012, 39, 112–119. [Google Scholar] [CrossRef] [PubMed]
- Dos Santos, B.M.; Pereira, G.C.; Piton, E.; Fialho, M.F.P.; Becker, G.; da Silva Carlotto, M.; Oliveira, S.M.; Trevisan, G.; Zanchet, E.M.; Pillat, M.M.; et al. Lower antidepressant response to fluoxetine is associated with anxiety-like behavior, hippocampal oxidative imbalance, and increase on peripheral IL-17 and IFN-γ levels. Behav. Brain Res. 2022, 425, 113815. [Google Scholar] [CrossRef]
- Fava, M.; Rush, A.J.; Alpert, J.E.; Balasubramani, G.K.; Wisniewski, S.R.; Carmin, C.N.; Biggs, M.M.; Zisook, S.; Leuchter, A.; Howland, R.; et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: A STAR*D report. Am. J. Psychiatry 2008, 165, 342–351. [Google Scholar] [CrossRef]
- Wu, Z.; Chen, J.; Yuan, C.; Hong, W.; Peng, D.; Zhang, C.; Cao, L.; Fang, Y. Difference in remission in a Chinese population with anxious versus nonanxious treatment-resistant depression: A report of OPERATION study. J. Affect. Disord. 2013, 150, 834–839. [Google Scholar] [CrossRef] [PubMed]
- Yin, J.-B.; Liu, H.-X.; Shi, W.; Ding, T.; Hu, H.-Q.; Guo, H.-W.; Jin, S.; Wang, X.-L.; Zhang, T.; Lu, Y.-C.; et al. Various BDNF administrations attenuate SPS-induced anxiety-like behaviors. Neurosci. Lett. 2022, 788, 136851. [Google Scholar] [CrossRef]
- Molendijk, M.L.; Bus, B.A.A.; Spinhoven, P.; Penninx, B.W.J.H.; Prickaerts, J.; Oude Voshaar, R.C.; Elzinga, B.M. Gender specific associations of serum levels of brain-derived neurotrophic factor in anxiety. World J. Biol. Psychiatry 2012, 13, 535–543. [Google Scholar] [CrossRef]
- Ball, S.; Marangell, L.B.; Lipsius, S.; Russell, J.M. Brain-derived neurotrophic factor in generalized anxiety disorder: Results from a duloxetine clinical trial. Prog. Neuropsychopharmacol. Biol. Psychiatry 2013, 43, 217–221. [Google Scholar] [CrossRef]
- Kobayashi, K.; Shimizu, E.; Hashimoto, K.; Mitsumori, M.; Koike, K.; Okamura, N.; Koizumi, H.; Ohgake, S.; Matsuzawa, D.; Zhang, L.; et al. Serum brain-derived neurotrophic factor (BDNF) levels in patients with panic disorder: As a biological predictor of response to group cognitive behavioral therapy. Prog. Neuropsychopharmacol. Biol. Psychiatry 2005, 29, 658–663. [Google Scholar] [CrossRef]
- Duman, R.S.; Monteggia, L.M. A neurotrophic model for stress-related mood disorders. Biol. Psychiatry 2006, 59, 1116–1127. [Google Scholar] [CrossRef]
- Miller, B.R.; Hen, R. The current state of the neurogenic theory of depression and anxiety. Curr. Opin. Neurobiol. 2015, 30, 51–58. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Li, P.; Ma, X.; Zhang, J.; Sun, X.; Luo, X.; Zhang, Y. Association between plasma levels of BDNF and GDNF and the diagnosis, treatment response in first-episode MDD. J. Affect. Disord. 2022, 315, 190–197. [Google Scholar] [CrossRef]
- Yoshimura, R.; Okamoto, N.; Chibaatar, E.; Natsuyama, T.; Ikenouchi, A. The Serum Brain-Derived Neurotrophic Factor Increases in Serotonin Reuptake Inhibitor Responders Patients with First-Episode, Drug-Naïve Major Depression. Biomedicines 2023, 11, 584. [Google Scholar] [CrossRef] [PubMed]
- Lopez, J.P.; Mamdani, F.; Labonte, B.; Beaulieu, M.-M.; Yang, J.P.; Berlim, M.T.; Ernst, C.; Turecki, G. Epigenetic regulation of BDNF expression according to antidepressant response. Mol. Psychiatry 2013, 18, 398–399. [Google Scholar] [CrossRef]
- Cubillos, S.; Engmann, O.; Brancato, A. BDNF as a Mediator of Antidepressant Response: Recent Advances and Lifestyle Interactions. Int. J. Mol. Sci. 2022, 23, 14445. [Google Scholar] [CrossRef]
- Brunoni, A.R.; Lopes, M.; Fregni, F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: Implications for the role of neuroplasticity in depression. Int. J. Neuropsychopharmacol. 2008, 11, 1169–1180. [Google Scholar] [CrossRef]
- Molendijk, M.L.; Spinhoven, P.; Polak, M.; Bus, B.A.A.; Penninx, B.W.J.H.; Elzinga, B.M. Serum BDNF concentrations as peripheral manifestations of depression: Evidence from a systematic review and meta-analyses on 179 associations (N = 9484). Mol. Psychiatry 2014, 19, 791–800. [Google Scholar] [CrossRef]
- Jiang, H.; Chen, S.; Li, C.; Lu, N.; Yue, Y.; Yin, Y.; Zhang, Y.; Zhi, X.; Zhang, D.; Yuan, Y. The serum protein levels of the tPA-BDNF pathway are implicated in depression and antidepressant treatment. Transl. Psychiatry 2017, 7, e1079. [Google Scholar] [CrossRef] [PubMed]
- Kishi, T.; Yoshimura, R.; Ikuta, T.; Iwata, N. Brain-Derived Neurotrophic Factor and Major Depressive Disorder: Evidence from Meta-Analyses. Front. Psychiatry 2017, 8, 308. [Google Scholar] [CrossRef]
- Björkholm, C.; Monteggia, L.M. BDNF—A key transducer of antidepressant effects. Neuropharmacology 2016, 102, 72–79. [Google Scholar] [CrossRef]
- Lee, B.-H.; Kim, H.; Park, S.-H.; Kim, Y.-K. Decreased plasma BDNF level in depressive patients. J. Affect. Disord. 2007, 101, 239–244. [Google Scholar] [CrossRef] [PubMed]
- Na, K.-S.; Won, E.; Kang, J.; Chang, H.S.; Yoon, H.-K.; Tae, W.S.; Kim, Y.-K.; Lee, M.-S.; Joe, S.-H.; Kim, H.; et al. Brain-derived neurotrophic factor promoter methylation and cortical thickness in recurrent major depressive disorder. Sci. Rep. 2016, 6, 21089. [Google Scholar] [CrossRef] [PubMed]
- Xiao, Z.; Liu, W.; Gao, K.; Wan, Q.; Yang, C.; Wang, H.; Wang, X.; Wang, G.; Liu, Z. Interaction between CRHR1 and BDNF genes increases the risk of recurrent major depressive disorder in Chinese population. PLoS ONE 2011, 6, e28733. [Google Scholar] [CrossRef]
- Wolkowitz, O.M.; Wolf, J.; Shelly, W.; Rosser, R.; Burke, H.M.; Lerner, G.K.; Reus, V.I.; Nelson, J.C.; Epel, E.S.; Mellon, S.H. Serum BDNF levels before treatment predict SSRI response in depression. Prog. Neuropsychopharmacol. Biol. Psychiatry 2011, 35, 1623–1630. [Google Scholar] [CrossRef] [PubMed]
- Mikoteit, T.; Beck, J.; Eckert, A.; Hemmeter, U.; Brand, S.; Bischof, R.; Holsboer-Trachsler, E.; Delini-Stula, A. High baseline BDNF serum levels and early psychopathological improvement are predictive of treatment outcome in major depression. Psychopharmacology 2014, 231, 2955–2965. [Google Scholar] [CrossRef] [PubMed]
- Kheirouri, S.; Noorazar, S.G.; Alizadeh, M.; Dana-Alamdari, L. Elevated Brain-Derived Neurotrophic Factor Correlates Negatively with Severity and Duration of Major Depressive Episodes. Cogn. Behav. Neurol. 2016, 29, 24–31. [Google Scholar] [CrossRef]
- Chu, L.; Sun, X.; Jia, X.; Li, D.; Gao, P.; Zhang, Y.; Li, J. The Relationship Among BDNF Val66Met Polymorphism, Plasma BDNF Level, and Trait Anxiety in Chinese Patients With Panic Disorder. Front. Psychiatry 2022, 13, 932235. [Google Scholar] [CrossRef]
- Li, J.; Li, R.; Li, D.; Zhang, J.; Luo, X.; Zhang, Y. Serum BDNF levels and state anxiety are associated with somatic symptoms in patients with panic disorder. Front. Psychiatry 2023, 14, 1168771. [Google Scholar] [CrossRef]
- Troyan, A.S.; Levada, O.A. The Diagnostic Value of the Combination of Serum Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor-1 for Major Depressive Disorder Diagnosis and Treatment Efficacy. Front. Psychiatry 2020, 11, 800. [Google Scholar] [CrossRef]
- Lee, J.; Lee, K.H.; Kim, S.H.; Han, J.Y.; Hong, S.-B.; Cho, S.-C.; Kim, J.-W.; Brent, D. Early changes of serum BDNF and SSRI response in adolescents with major depressive disorder. J. Affect. Disord. 2020, 265, 325–332. [Google Scholar] [CrossRef]
- Zheng, W.; Jiang, M.-L.; He, H.-B.; Li, R.-P.; Li, Q.-L.; Zhang, C.-P.; Zhou, S.-M.; Yan, S.; Ning, Y.-P.; Huang, X. Serum BDNF Levels are Not Associated with the Antidepressant Effects of Nonconvulsive Electrotherapy. Neuropsychiatr. Dis. Treat. 2020, 16, 1555–1560. [Google Scholar] [CrossRef] [PubMed]
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5-TR; American Psychiatric Association Publishing: Washington, DC, USA, 2022. [Google Scholar]
- AMAI [Asociación Mexicana de Agencias de Inteligencia de Mercado y Opinión Pública] Cuestionario NSE AMAI 2022. Available online: https://www.amai.org/descargas/CUESTIONARIO_AMAI_2022.pdf (accessed on 28 August 2024).
- Cusin, C.; Yang, H.; Yeung, A.; Fava, M. Rating Scales for Depression. In Handbook of Clinical Rating Scales and Assessment in Psychiatry and Mental Health; Baer, L., Blais, M.A., Eds.; Humana Press: Totowa, NJ, USA, 2010; pp. 7–35. [Google Scholar]
- Bobo, W.V.; Angleró, G.C.; Jenkins, G.; Hall-Flavin, D.K.; Weinshilboum, R.; Biernacka, J.M. Validation of the 17-item Hamilton Depression Rating Scale definition of response for adults with major depressive disorder using equipercentile linking to Clinical Global Impression scale ratings: Analysis of Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) data. Hum. Psychopharmacol. 2016, 31, 185–192. [Google Scholar] [PubMed]
- Julian, L.J. Measures of anxiety: State-Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), and Hospital Anxiety and Depression Scale-Anxiety (HADS-A). Arthritis Care Res. 2011, 63 (Suppl. S11), S467–S472. [Google Scholar] [CrossRef]
- Silva, C.; Medina, A.H.; Cruz, B.E.J.; Alvarado, N. Revisión de la estructura interna de la subescala de rasgo del Inventario de Ansiedad Rasgo-Estado para jóvenes de habla hispana. Psic. Sal. 2016, 26, 253–262. [Google Scholar]
Responders n = 21 | Non-Responders n = 19 | Statistic | |
---|---|---|---|
Demographic Features | |||
Gender n (%) | χ2 = 0.93, df = 1, p = 0.45 | ||
Women | 15 (71.4) | 16 (84.2) | |
Men | 6 (28.6) | 3 (15.8) | |
Age (years) Mean S.D. | 33.5 (11.71) | 31.8 (11.27) | t = −4.75, df = 38, p = 0.63 |
Marital status n (%) | χ2 = 6.05, df = 3, p = 0.109 | ||
Single | 13 (61.9) | 15 (78.9) | |
Partnered | 6 (28.6) | 2 (10.5) | |
Separated/divorced | 0 (0.0) | 2 (10.5) | |
Widow | 2 (9.5) | 0 (0.0) | |
Education n (%) | χ2 = 1.03, df = 3, p = 0.793 | ||
Elementary school | 1 (4.8) | 1 (5.3) | |
High school | 9 (42.9) | 6 (31.6) | |
College | 9 (42.9) | 11 (57.9) | |
Graduate school | 2 (9.5) | 1 (5.3) | |
Occupation n (%) | χ2 = 3.34, df = 3, p = 0.342 | ||
Unemployed | 6 (28.6) | 4 (21.1) | |
Employed | 6 (28.6) | 5 (26.3) | |
Students | 5 (23.8) | 9 (47.4) | |
Other | 4 (19) | 1 (5.3) | |
Religion n (%) | χ2 = 7.116, df = 3, p = 0.068 | ||
Atheist | 6 (28.6) | 8 (42.1) | |
Catholic | 13 (61.9) | 6 (31.6) | |
Christian | 0 (0.0) | 4 (21.1) | |
Other | 2 (9.5) | 1 (5.3) |
Responders n = 21 | Non-Responders n = 19 | Statistic | |
---|---|---|---|
Clinical Characteristics | |||
Mean (S.D.) | Mean (S.D.) | ||
Basal HDRS | 23.04 (4.32) | 22.26 (4.4) | t = −0.56, df 38, p = 0.28 |
Basal STAI-S | 50.30 (16.96) | 48.94 (19.23) | t = −0.23, df 38, p = 0.81 |
BDNF | 29.98 (3.66) | 20.16 (2.27) | t = −6.65, df 38, p = 0.0001 |
BMI | 24.35 (4.13) | 27.24 (7.47) | t = −1.50, df 38, p = 0.14 |
LDE n (%) | |||
1.00 | 7 (58.3) | 5 (41.7) | χ2 = 1.27, df 2, p = 0.52 |
2.00 | 0 (0.0) | 1 (100) | |
3.00 | 14 (51.9) | 13 (48.1) | |
PDE n (%) | |||
1.00 | 12 (57.1) | 4 (21.1) | χ2 = 6.16, df 2, p = 0.046 |
2.00 | 2 (9.5) | 6 (31.6) | |
3.00 | 7 (33.3) | 9 (47.4) | |
Antidepressant n (%) | χ2 = 0.57, df 3, p = 0.902 | ||
Citalopram | 1 (4.8) | 2 (10.5) | |
Escitalopram | 4 (19.0) | 3 (15.8) | |
Fluoxetine | 11 (52.4) | 9 (47.4) | |
Sertraline | 5 (23.8) | 5 (26.3) |
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Flores-Ramos, M.; Vega-Rosas, A.; Palomera-Garfias, N.; Saracco-Alvarez, R.; Ramírez-Rodríguez, G.B. Are BDNF and Stress Levels Related to Antidepressant Response? Int. J. Mol. Sci. 2024, 25, 10373. https://doi.org/10.3390/ijms251910373
Flores-Ramos M, Vega-Rosas A, Palomera-Garfias N, Saracco-Alvarez R, Ramírez-Rodríguez GB. Are BDNF and Stress Levels Related to Antidepressant Response? International Journal of Molecular Sciences. 2024; 25(19):10373. https://doi.org/10.3390/ijms251910373
Chicago/Turabian StyleFlores-Ramos, Mónica, Andrés Vega-Rosas, Nadia Palomera-Garfias, Ricardo Saracco-Alvarez, and Gerardo Bernabé Ramírez-Rodríguez. 2024. "Are BDNF and Stress Levels Related to Antidepressant Response?" International Journal of Molecular Sciences 25, no. 19: 10373. https://doi.org/10.3390/ijms251910373
APA StyleFlores-Ramos, M., Vega-Rosas, A., Palomera-Garfias, N., Saracco-Alvarez, R., & Ramírez-Rodríguez, G. B. (2024). Are BDNF and Stress Levels Related to Antidepressant Response? International Journal of Molecular Sciences, 25(19), 10373. https://doi.org/10.3390/ijms251910373