Serum brain-derived neurotrophic factor, Val66Met polymorphism and open-label SSRI treatment response in Major Depressive Disorder.
Psychoneuroendocrinology
; 165: 107045, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38636352
ABSTRACT
BACKGROUND:
Brain-derived neurotrophic factor (BDNF) has been implicated in the therapeutic action of antidepressants and possibly in the pathophysiology of Major Depressive Disorder (MDD). Clinical studies of peripheral blood levels of BDNF in MDD have provided conflicting results, and there are also conflicting reports regarding the predictive value of peripheral BDNF levels for antidepressant treatment response. The present study investigated the association between serum BDNF levels, the BDNF Val66Met polymorphism (rs6265), clinical characteristics and SSRI treatment response.METHODS:
This open-label clinical trial included 99 physically healthy, unmedicated MDD participants and 70 healthy controls. Following a baseline assessment, 53 of the MDD participants completed an eight-week, open-label course of SSRI antidepressant treatment. Serum BDNF levels and Hamilton Rating Scale for Depression (HDRS) ratings were examined at baseline and after eight weeks of treatment. Antidepressant response was defined as a decrease in HDRS ratings of > 50% from baseline to the end-of-treatment. Finally, serum BDNF levels and SSRI treatment response were compared between MDD participants who were heterozygous or homozygous for the Met allele ("Met-carriers") and individuals homozygous for the Val allele.RESULTS:
Serum BDNF levels at baseline were significantly higher in the unmedicated MDD participants compared to healthy controls (15.90â¯ng/ml vs 13.75â¯ng/ml, t (167) = -2.041, p = 0.043). In a post-hoc analysis, this difference was seen in the female but not male participants (16.85â¯ng/ml vs 14.06â¯ng/ml, t (91) = -2.067, p = 0.042; 14.86â¯ng/ml vs 13.31â¯ng/ml, t (74) = -0.923, p = 0.359). Baseline serum BDNF levels were not associated with treatment responder status or with absolute change in depression ratings over the course of 8-week SSRI treatment (p = 0.599). In both Responders and Non-responders, no significant changes in serum BDNF levels were found over the 8-week period of SSRI-treatment (16.32â¯ng/ml vs 16.23â¯ng/ml, t (18) = 0.060, p = 0.953; 16.04â¯ng/ml vs 15.61â¯ng/ml, t (29) = 0.438, p = 0.665, respectively). Further, no differences were found in serum BDNF levels prior to treatment between MDD Met-carriers and MDD Val/Val homozygotes (15.32â¯ng/ml vs 16.36â¯ng/ml, t (85) = 0.747, p = 0.457), and no differences were found in post-treatment serum BDNF (F1,42= 0.031, p = 0.862). However, MDD Val/Val homozygotes showed significantly greater antidepressant responses at week 8 than did MDD Met-carriers (F1,46 = 4.366, p = 0.043).CONCLUSION:
Our results do not support sufficient reliability of using peripheral BDNF to characterize depression or to predict antidepressant response in clinical use. The role of sex in moderating BDNF differences in depression, and the role of BDNF gene polymorphisms in predicting antidepressant response, remain to be further investigated. We conclude that, while central nervous system BDNF is likely involved in antidepressant efficacy and in aspects of MDD pathophysiology, its reflection in serum BDNF levels is of limited diagnostic or prognostic utility.Palabras clave
Texto completo:
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores Selectivos de la Recaptación de Serotonina
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Factor Neurotrófico Derivado del Encéfalo
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Polimorfismo de Nucleótido Simple
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Trastorno Depresivo Mayor
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Psychoneuroendocrinology
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos