BDNF levels were significantly decreased in both mania (SMD −0.54, 95% CI −1.03 to −0.06, P = 0.03, I2 = 91%, k = 13, n = 946) and bipolar depression (SMD −0.86, 95% CI −1.38 to −0.34, P < 0.00001, I2 = 91%, k = 13, n = 949), whereas in euthymia there was no significant difference (SMD 0.12, 95% CI −0.11 to 0.35, P = 0.32, I2 = 77%, k = 14, n = 1447) (Fig. 4). This evidence concerns the gene BDNF and bipolar disorder.