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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.

Background/Aims: Dopamine is an important neurotransmitter involved in the pathophysiology of depression and anhedonia. Dopamine transporters (DAT) may play a crucial role in the pathophysiology of dopaminergic transmission. We investigated the relationship between striatal DAT availability and depression, pointing out possible correlations with anhedonia and treatment outcomes. Methods: Ten depressed patients with anhedonia, 10 depressed patients without anhedonia and 20 healthy controls underwent single photon emission computed tomography using 123I-FP-CIT [123I-N-ω-fluoropropyl-carbomethoxy-3β-(4-iodophenyl)tropane]. Psychometric measures included the Snaith-Hamilton Pleasure Scale and the Hamilton Depression Rating Scale. A further assessment of DAT availability was performed in the 10 patients with marked anhedonia after a 3-month pharmacological treatment. Results: Depressed patients with and without anhedonia showed significantly lower 123I-FP-CIT binding ratios in the bilateral striatum, caudate and putamen. No significant changes were detected after treatment in the 10 patients with marked anhedonia. When considering clinical outcomes, subjects with remission of depression showed a significant reduction of 123I-FP-CIT binding ratios in all regions at baseline, but after treatment no differences were found any longer. Conclusions: We suppose that a hypofunction of the striatal dopaminergic system may be a ‘state' feature of a depressive condition as a whole rather than anhedonia itself. On the other hand, some anhedonic features mainly represent an enduring trait that persists independently of mood state.