Background: Previous evidence suggested the possible association of FK506 binding protein 5 (FKBP5) gene variants in bipolar disorder (BPD). Objective: Given the need of refinement of the findings obtained in large but poorly phenotyped samples, this study investigated the possible role of variants within FKBP5 in a small but deeply phenotyped BPD sample. Methods: A sample (N = 131) of bipolar patients were investigated with 10 polymorphisms within the FKBP5 gene. A control sample (N = 65) was also used for the analyses. Treatment response and remission of symptoms were evaluated using of the Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Young Mania Rating Scale (YMRS). The same analyses were also performed on the depressive subsample of BPD (D.BPD). Results: rs3800373 was associated with disorder risk in the depressive BPD subsample with the G allele being more frequent in subjects with a D.BPD phenotype. This was the only association that survived statistical correction. Conclusions: rs3800373 FKBP5 may increase the risk of developing predominantly depressed BPD, probably through the creation of an enhancer consensus sequence in the 3′UTR of the gene, thus potentially increasing its expression. This finding seems to be partially supported by literature data, which evidenced increased levels of FKBP5 in psychiatric subjects.

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