Brain-derived neurotrophic factor serum levels in genetically isolated populations: gender-specific association with anxiety disorder subtypes but not with anxiety levels or Val66Met polymorphism

Davide Carlino, Ruggiero Francavilla, Gabriele Baj, Karolina Kulak, Pio d'Adamo, Sheila Ulivi, Stefania Cappellani, Paolo Gasparini, Enrico Tongiorgi, Davide Carlino, Ruggiero Francavilla, Gabriele Baj, Karolina Kulak, Pio d'Adamo, Sheila Ulivi, Stefania Cappellani, Paolo Gasparini, Enrico Tongiorgi

Abstract

Anxiety disorders (ADs) are disabling chronic disorders with exaggerated behavioral response to threats. This study was aimed at testing the hypothesis that ADs may be associated with reduced neurotrophic activity, particularly of Brain-derived neurotrophic factor (BDNF), and determining possible effects of genetics on serum BDNF concentrations. In 672 adult subjects from six isolated villages in North-Eastern Italy with high inbreeding, we determined serum BDNF levels and identified subjects with different ADs subtypes such as Social and Specific Phobias (PHSOC, PHSP), Generalized Anxiety Disorder (GAD), and Panic Disorder (PAD). Analysis of the population as a whole or individual village showed no significant correlation between serum BDNF levels and Val66Met polymorphism and no association with anxiety levels. Stratification of subjects highlighted a significant decrease in serum BDNF in females with GAD and males with PHSP. This study indicates low heritability and absence of any impact of the Val66Met polymorphism on circulating concentrations of BDNF. Our results show that BDNF is not a general biomarker of anxiety but serum BDNF levels correlate in a gender-specific manner with ADs subtypes.

Keywords: Anxiety; Brain-derived neurotrophic factor; Generalized Anxiety Disorder; Genome wide analysis; Neurotrophins; Serum biomarkers; Sex factors; Social Phobia; Specific Phobia; Val66Met polymorphism.

Conflict of interest statement

The authors declare there are no competing interests, either financial or non-financial.

Figures

Figure 1. Serum BDNF level in Healthy…
Figure 1. Serum BDNF level in Healthy donors (n = 420) and Anxiety disorders Patients (n = 252).
(A) BDNF values are not normally distributed. Mann–Whitney U Test 1-tail, revealed no significant statistical difference between the two groups (p = 0.060). (B) Serum BDNF level in male and female groups; n, number of subjects [healthy donors, patients]; male [219, 71], female [201, 181].
Figure 2. Serum BDNF levels in six…
Figure 2. Serum BDNF levels in six villages of the Genetic Park of Friuli Venezia Giulia; n, number of subjects [healthy controls, patients].
(A) Clauzetto [69, 54], (B) Erto [27, 18], (C) Illegio [75, 50], (D) Resia [139, 49], (E) San Martino [73, 38], (F) Sauris [40, 43]. A comparison Mann–Whitney U Test 1-tail shows no difference among the control and patient groups in all villages.
Figure 3. Serum BDNF in different diagnostic…
Figure 3. Serum BDNF in different diagnostic categories of Anxiety Disorder.
(A) Box Plot Graph showing the distribution of serum BDNF levels between different diagnostic categories of anxiety disorders. (B–D) Linear regression analysis of serum BDNF levels and severity of disease in 3 different categories of anxiety disorders measured with HAM-A (Hamilton Anxiety Rating Scale).
Figure 4. Analysis of BDNF levels gender…
Figure 4. Analysis of BDNF levels gender differences in Generalized Anxiety Disorders and Specific Phobia.
(A) Serum BDNF level in male and female groups affected by Generalized Anxiety Disorder; n, number of subjects [healthy donors, patients]; male [219, 28], female [201, 63]. Comparison using Mann–Whitney U Test 1-tail shows significant statistical difference in serum BDNF level between the two groups in female subjects (∗, p = 0.025). (B) Serum BDNF level in male and female groups affected by Specific Phobia; male [219, 15], female [201, 82]. Comparison Mann–Whitney U Test 1-tail shows significant statistical difference in serum BDNF level between the two groups in male subjects (∗, p = 0.018). Abbreviation: HD, Healthy Donors; GAD, Generalized Anxiety Disorders; PHSP, Specific Phobia.

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