Telomere Length in Schizophrenia
Adrienne Maguire, MS2 and Rachel Loewy, PhD
University of California Davis, School of Medicine; University of California, San Francisco
Telomeres
• Telomeres are tandem repeat sequences (TTAGGG) at
the end of linear eukaryotic DNA (15)
• These repeats protect chromosomes from being
recognized as damaged DNA, help to regulate gene
expression, and participate in controlling cell replication
and entry into senescence (1, 2)
• Cell division, and thus aging, leads to progressive
telomere shortening
• Critically short telomeres cause cell checkpoint genes to
be activated (TP53) and the cells with dysfunctional
telomeres undergo apoptosis (2)
• Shortened telomeres have been associated with CVD,
stroke, obesity, cancer, T2DM, and other chronic
illnesses (1, 2, 5, 9, 28)
Telomeres in Psychiatric Illness
A meta-analysis in 2015 showed shorter TL across
psychiatric disorders (3)
MDD
• A majority of the studies done on MDD and telomere
length have found that there is shortening (3, 22)
• Some studies have suggested that the shortening is
more pronounced in groups that have had a longer
duration of illness and a more severe manifestation of
MDD, linking these findings to measures of oxidative
stress and inflammation (23, 24)
• Researchers are looking further into the relationship
between depression, anti-depressants, treatment
responsiveness and telomerase levels (13, 25)
Bipolar Disorder
• There is more conflicting evidence for TL in BD – some
studies show longer, others show shorter, and some
show no difference between BD and HC (21, 22)
• Some evidence of those who are good responders to
Lithium have longer TL (13)
Anxiety/PTSD
• Some conflicting evidence between shorter TL and no
difference compared to controls (3, 6, 7, 10, 12, 17)
• Some of this evidence points to shortened LTL in those
exposed to childhood adversity (7)
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Telomeres in Schizophrenia
• Schizophrenia has been described as a disorder of
aging (3, 8, 11, 18, 19)
• There has been conflicting evidence on whether TL is
shortened or elongated in SCZ, but a recent meta-
analysis reveals there is more evidence that TL is
shortened in SCZ (3, 4, 8, 11, 16, 18, 19, 26)
• Some studies have found shorter TL in those with more
severe disease, speculating that there could be greater
lifetime exposure to oxidative stress and pathological
damage, leading to accelerated ageing (11, 18, 19)
• One study looked at the difference in TL between SCZ
inpatients who were good responders versus poor
responders to antipsychotic medications and found that
the poor responders had shorter LTL compared to good
responders and healthy controls (26)
• Other studies have found no correlation with TL and
lifetime exposure to antipsychotics (8)
• Studies on telomerase activity in SCZ have also
revealed conflicting evidence (20, 26)
• Overall, many of these studies have had low sample
sizes
• Many studies have not controlled well for somatic and/or
psychiatric co-morbidities, nor for lifestyle conditions
(diet, exercise, smoking, BMI)
UHR and Telomeres
• Ultra-High-Risk youth have been of increasing interest in
the identification and intervention for those at risk of
developing schizophrenia
• It is estimated that up to 35% of those identified as UHR
experience a psychotic episode within 2.5 years of
identification (27)
• Very little research has been done on UHR groups and
telomere length
• One study has been done on this group that revealed
there was shorter LTL in UHR groups as compared to
controls that were adjusted for age, sex, ethnicity, and
education (14)
• This could imply that there are, in fact, telomere erosion
present early in disease before the onset of full
psychosis
• This study had a small sample size (n=110, only 22 UHR
subjects) ; more research should be done in this group
Future Directions REFERENCES
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Stress
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SCZ Low TA Schizophr Res. 2008;106(2-3):242-
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ABBREVIATIONS 24. Wolkowitz OM, Mellon SH, Epel ES, et al. Leukocyte telomere length in major depression:
correlations with chronicity, inflammation and oxidative stress--preliminary findings. PLoS ONE.
2011;6(3):e17837.
TL = Telomere Length 25. Wolkowitz OM, Mellon SH, Epel ES, et al. Resting leukocyte telomerase activity is elevated in
major depression and predicts treatment response. Mol Psychiatry. 2012;17(2):164-72.
MDD = Major Depressive Disorder
26. Yu WY, Chang HW, Lin CH, Cho CL. Short telomeres in patients with chronic schizophrenia who
BD = Bipolar Disorder show a poor response to treatment. J Psychiatry Neurosci. 2008;33(3):244-7.
27. Yung AR, Phillips LJ, Yuen HP, Mcgorry PD. Risk factors for psychosis in an ultra high-risk group:
PTSD = Post-Traumatic Stress Disorder psychopathology and clinical features. Schizophr Res. 2004;67(2-3):131-42.
SCZ = Schizophrenia 28. Zhang C, Chen X, Li L, Zhou Y, Wang C, Hou S. The Association between Telomere Length and
Cancer Prognosis: Evidence from a Meta-Analysis. PLoS ONE. 2015;10(7):e0133174.
UHR = Ultra-High-Risk
ACE = Adverse Childhood Experiences CONTACT
TA = Telomerase Activity
Adrienne Maguire: ammaguire@ucdavis.edu
Rachel Loewy: Rachel.Loewy@ucsf.edu