BDNF as a Mediator of Antidepressant Response: Recent Advances and Lifestyle Interactions
Abstract
:1. The Paradigm Shift in Antidepressant Mechanism of Action
2. BDNF as a Critical Antidepressant Mediator
2.1. BDNF Exerts Distinct Effects in MDD-Linked Brain Regions
2.2. Multiple Cell Types Contribute to Increased BDNF Following Antidepressant Treatment
2.3. Epigenetic Regulation of the Bdnf Gene
3. Lifestyle Interactions with Antidepressants in Rodent Models and Humans
3.1. Nutrition
3.2. Environment
3.3. Aging
Adjunctive Nutrient | Antidepressant | Outcome | Reference |
---|---|---|---|
Omega-3 PUFA 1000 mg/d | Sertraline | MADRS: Omega-3 PUFA < placebo | [81] |
Ethyl-EPA 1 g/d | Fluoxetine 20 mg/d | HDRS: Ethyl-EPA < placebo | [79] |
EPA 1, 2 or 4 g/d | Unspecified antidepressants | HDRS EPA < placebo (best 1 g/d) | [82] |
EPA 2 g/d | Unspecified antidepressants | HDRS EPA < placebo | [84] |
DHA 260 mg/d or 520 mg/d | Unspecified antidepressants | HDRS < after treatment resistance | [87] |
EPA 1.8 g/d + DHA 0.4 g/d | Citalopram 20–40 mg/d | HDRS: Fatty acids < placebo | [88] |
EPA 0.93 g/d + DHA 0.75 g/d | Sertraline 50 mg/d | BDI-II or HDRS: Fatty acids = placebo | [80] |
EPA 1 g/d, DHA 1 g/d | Unspecified antidepressants | HDRS: EPA < DHA or placebo | [86] |
EPA + DHA 3 g/d (EPA 0.6 g; DHA 2.4 g) | Unspecified antidepressants | HDRS-SF: EPA + DHA = placebo | [85] |
EPA + DHA 9.6 g/d | Unspecified antidepressants | HDRS EPA + DHA < placebo | [83] |
Palmitoylethanolamide 1200 mg/d | Citalopram 20 mg/d | HDRS: Palmitoylethanolamide < placebo | [90] |
Creatine 4 mg/d | Fluoxetine 20–40 mg/d | CDRS-R: Creatine < placebo | [104] |
Creatine 5 g/d | Escitalopram 20 mg/d | HDRS: creatine < placebo | [103] |
Tryptophan 4 g/d | Fluoxetine 20 mg/d | HDRS: Tryptophan < placebo | [110] |
DL-Tryptophan 0.1 g/kg body weight | Chlorimipramine 150 mg/d | Cronholm-Ottosson Depression Scale: n.s. | [111] |
DL-Tryptophan 12, 15, 18 g depending on body weight | Phenelzine 60 mg/d | HDRS: DL-Tryptophan < placebo | [112] |
SAMe 800 mg/d | Unspecified antidepressants | HDRS: < after treatment resistance | [206,207] |
SAMe 1600 mg/d | SSRIs | HDRS: SAMe < placebo (in treatment resistance) | [116] |
SAMe 200 mg/d, NAC 200 mg/d and folate 200 ug/d | SSRIs | HADS-A and CGI: better with SAMe, NAC and folate | [114] |
L-Methylfolate 15 mg/d | SSRIs | QIDS-SR and CGI: better with L-Methylfolate in SSRI resistance | [129] |
L-Methylfolate | SSRIs/SNRIs | CGI: L-Methylfolate < placebo | [130] |
Folic acid 0.5 mg/d | Fluoxetine 20 mg/d | HDRS: Folic acid < placebo | [126] |
Folic acid 10 mg/d | Fluoxetine 20 mg/d | HDRS: Folic acid < placebo | [127] |
Folic acid 5 mg/d | Unspecified antidepressants | BDI-II: Folic acid = placebo | [131] |
Folic acid 2 mg/d + Vitamin B12 0.5 mg/d + Vitamin B6 25 mg/d | Citalopram 20–40 mg/d | MADRS: Folic acid + B12 + B6 = placebo | [135] |
Folic acid 400 ug/d + Vitamin B12 100 ug/d | Unspecified antidepressants | PHQ-9: n.s. | [134] |
Vitamin B12 1 mg/d | SSRIs 20–40 mg/d | HDRS: with Vitamin B12 < placebo | [132] |
TCA 100–200 mg/d | HDRS: with Vitamin B12 < placebo | [132] | |
Vitamin C 1 g/d | Fluoxetine 10–20 mg/d | CDRS: with Vitamin C < placebo | [136] |
Citalopram 20 mg/d | HDRS: with Vitamin C = placebo | [138] | |
Vitamin D3 1500IU/d | Fluoxetine 20 mg/d | HDRS: with Vitamin D3 < placebo | [137] |
Vitamin D3 300.000 U | Unspecified antidepressants | HDRS with Vitamin D3 < placebo (after 4 weeks) | [139] |
Zinc 25 mg/d | Fluoxetine 20–60 mg/d | BDI: Zinc < placebo | [148] |
Citalopram 20–60 mg/d | BDI: Zinc < placebo | [148] | |
Imipramine 100–200 mg/d | BDI, HDRS, CGI, MADRS: Zinc < placebo | [150,151] | |
Unspecified antidepressants | HDRS, BDI: Zinc < placebo | [208] | |
Magnesium 120 mg/d | Fluoxetine 20–40 mg/d | HDRS: Magnesium = placebo | [154] |
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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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. https://doi.org/10.3390/ijms232214445
Cubillos S, Engmann O, Brancato A. BDNF as a Mediator of Antidepressant Response: Recent Advances and Lifestyle Interactions. International Journal of Molecular Sciences. 2022; 23(22):14445. https://doi.org/10.3390/ijms232214445
Chicago/Turabian StyleCubillos, Susana, Olivia Engmann, and Anna Brancato. 2022. "BDNF as a Mediator of Antidepressant Response: Recent Advances and Lifestyle Interactions" International Journal of Molecular Sciences 23, no. 22: 14445. https://doi.org/10.3390/ijms232214445