title: Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging.
abstract: Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets.
authors.affiliation: Department of Clinical Sciences, Section for Psychiatry, Lund University, Lund, Sweden; Department of Psychiatry, University of California San Francisco (UCSF), School of Medicine, San Francisco, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindqvist
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF), School of Medicine, San Francisco, CA, USA.
authors.forename: Elissa S
authors.initials: ES
authors.lastname: Epel
authors.affiliation: Department of OB-GYN and Reproductive Sciences, UCSF School of Medicine, San Francisco, CA, USA.
authors.forename: Synthia H
authors.initials: SH
authors.lastname: Mellon
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Dóra
authors.initials: D
authors.lastname: Révész
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Josine E
authors.initials: JE
authors.lastname: Verhoeven
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF), School of Medicine, San Francisco, CA, USA.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Reus
authors.affiliation: Department of Biochemistry and Biophysics, UCSF School of Medicine, San Francisco, CA, USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF), School of Medicine, San Francisco, CA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Mahan
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF), School of Medicine, San Francisco, CA, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hough
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF), School of Medicine, San Francisco, CA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rosser
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF), School of Medicine, San Francisco, CA, USA; Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: F Saverio
authors.initials: FS
authors.lastname: Bersani
authors.affiliation: Department of Biochemistry and Biophysics, UCSF School of Medicine, San Francisco, CA, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Blackburn
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF), School of Medicine, San Francisco, CA, USA. Electronic address: Owen.Wolkowitz@ucsf.edu.
authors.forename: Owen M
authors.initials: OM
authors.lastname: Wolkowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016922:Cellular Senescence / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008875:Middle Aged; D016615:Telomere / Q000378:metabolism*; D055815:Young Adult
keywords: Aging; Antidepressant; Anxiety; Bipolar affective disorder; Depression; Disease; Early life adversity; Inflammation; Leukocytes; Major depressive disorder; Manic-depression; Mortality; Neurotrophic; Oxidative stress; Post-traumatic stress disorder; Psychosis; Schizophrenia; Stress; Telomerase; Telomeres