Count of “dark telomere” on the track of a biomarker for lithium treatment in bipolar disorder

Bipolar disorder (BD) is a severe psychiatric illness affecting approximately 1%-2% of individuals worldwide. BD is characterized by alternating manic and depressive episodes. Lithium is one of the most effective long-term treatments for BD, but 30%–40% of patients, fail to respond, and there is currently no method to identify the good lithium responders before initiation of treatment (Oedegaard et al., 2016). In a recent study, we demonstrated by quantitative PCR (qPCR), that leukocyte telomere length (LTL) of lithium responders (LiRs) and non-responders (non-LiRs) was positively correlated with years of lithium therapy. However, we fail to find significant differences between LiRs and non-LiRs LTL. We also reported quantitative fluorescence in situ hybridization (qFISH), measuring changes in telomere fluorescence intensity, in a subset of 8 patients (4 LiRs and 4 non-LiRs). Results by qPCR and qFISH were significantly correlated, but still, we found no statistically significant differences in LiRs and non-LiRs (Squassina et al., 2016). Since evidence suggests that the number of short telomeres rather than LTL determines telomere dysfunction (Elvashagen et al., 2011), we focused on the presence/absence of fluorescence chromosome ends to test if the mere enumeration of signals could significantly distinguish LiRs from nonLIRs. For this purpose, we analyzed 20 metaphases from 8 patients and 7 age-matched healthy controls, for positive and negative fluorescent telomeres. The results indicated that the number of negative (dark) telomeres was significantly higher in non-LiRS than LiRs (p = 0.041). In contrast, we observe no statistically significant difference between BD patients and healthy subjects (p = 0.36). Verification and validation of our preliminary results will prove if a simple count of “dark telomeres” may provide a valid biomarker distinguishing bipolar patients responding to lithium treatment. Funding RAS and Fondazione Banco Sardegna