Abstract
Variation in telomere length is heritable and is currently considered a promising biomarker of susceptibility for neuropsychiatric disorders, particularly because of its association with memory function and hippocampal morphology. Here, we investigate telomere length in connection to familial risk and disease expression in bipolar disorder (BD). We used quantitative PCRs and a telomere-sequence to single-copy-gene-sequence ratio method to determine telomere length in genomic DNA extracted from buccal smears from 63 patients with BD, 74 first-degree relatives (49 relatives had no lifetime psychopathology and 25 had a non-BD mood disorder), and 80 unrelated healthy individuals. Participants also underwent magnetic resonance imaging to determine hippocampal volumes and cognitive assessment to evaluate episodic memory using the verbal paired associates test. Telomere length was shorter in psychiatrically well relatives (p=0.007) compared with unrelated healthy participants. Telomere length was also shorter in relatives (regardless of psychiatric status; p<0.01) and patients with BD not on lithium (p=0.02) compared with lithium-treated patients with BD. In the entire sample, telomere length was positively associated with left and right hippocampal volume and with delayed recall. This study provides evidence that shortened telomere length is associated with familial risk for BD. Lithium may have neuroprotective properties that require further investigation using prospective designs.
Highlights
Telomeres are DNA repeat structures (TTAGGG) at the end of each chromosome that undergo shortening during mitosis (Allsop et al, 1992; Stewart et al, 2012)
Telomere shortening has been associated with exposure to cellular stressors (Saretzki and Von Zglinicki, 2002), lifestyle factors (Valdes et al, 2005), and social adversity (Epel et al, 2004; Gianaros et al, 2007; Shalev et al, 2013), whereas telomerase, an enzyme that adds DNA sequence repeats (TTAGGG) onto the 3′ telomeric end, may reverse or mitigate this process (Allsop et al, 1992; Stewart et al, 2012)
Lithium treatment status was not associated with differences in age of onset, or Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) scores (p40.94)
Summary
Telomeres are DNA repeat structures (TTAGGG) at the end of each chromosome that undergo shortening during mitosis (Allsop et al, 1992; Stewart et al, 2012). Telomere shortening has been associated with exposure to cellular stressors (Saretzki and Von Zglinicki, 2002), lifestyle factors (Valdes et al, 2005), and social adversity (Epel et al, 2004; Gianaros et al, 2007; Shalev et al, 2013), whereas telomerase, an enzyme that adds DNA sequence repeats (TTAGGG) onto the 3′ telomeric end, may reverse or mitigate this process (Allsop et al, 1992; Stewart et al, 2012). Cell senescence or cell death is triggered when a critically short telomere length is reached (Stewart et al, 2012). Telomere length is considered a promising biomarker of biological aging and susceptibility to disease (Calado and Young, 2009; Heidinger et al, 2011).
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