| 1. |
- Bersani, Francesco S, et al.
(författare)
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Telomerase activation as a possible mechanism of action for psychopharmacological interventions.
- 2015
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 20:11, s. 1305-1309
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Forskningsöversikt (refereegranskat)abstract
- Originally studied in relation to aging and cancer research, telomerase is now also investigated in relation to psychiatric disorders and treatments. Based on emerging clinical and preclinical data, we hypothesise that telomerase activation could represent a novel element mediating the mechanism of action of certain psychopharmacological interventions (e.g. antidepressants, lithium and antipsychotics). The modulation of intracellular Wnt/β-catenin or PI3K/Akt signalling pathways, the interaction with BDNF and 5-HT, and the antioxidant properties could represent possible mechanisms by which the different types of psychiatric medications could modulate telomerase activity. The potential of telomerase in promoting cellular survival and/or function in the brain and in the periphery could, in turn, represent a neurobiological substrate through which the enzyme can mediate the therapeutic effect of such interventions.
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| 2. |
- Darrow, Sabrina M., et al.
(författare)
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The Association Between Psychiatric Disorders and Telomere Length : A Meta-Analysis Involving 14,827 Persons
- 2016
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Ingår i: Psychosomatic Medicine. - 0033-3174. ; 78:7, s. 776-787
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: This study examined the relationship between leukocyte telomere length (LTL), a marker of cell aging, and psychiatric disorders in adults compared with controls using meta-analytic methods. METHODS: Data were abstracted from studies examining the relationship between LTL and adult psychiatric disorders. In addition to an overall estimate of effect size, subgroup analyses and meta-regression were performed to examine whether covariates (including psychiatric diagnoses) moderated the estimate. RESULTS: A significant overall effect size showing LTL shortening was found across all psychiatric disorders (Hedge g = −0.50, p <.001). Subgroup analyses did not demonstrate significant differences in effect size based on individual covariates (psychiatric disorder, sex, age, or assay method). The meta-regression indicated that although type of disorder and, likely, age moderate the overall effect size, the heterogeneity between studies could not be explained by a model that included these variables as well as sex and assay method. Although not significantly different, posttraumatic stress disorder, anxiety disorders, and depressive disorders had comparatively larger effect sizes (−1.27, −0.53, and −0.55), and psychotic and bipolar disorders had comparatively smaller ones (−0.23 and −0.26). CONCLUSIONS: We observed a robust effect size of LTL shortening for psychiatric disorders as a whole compared with controls. The results were less straightforward regarding relative differences in the strength of this association by specific disorder. Future studies should focus on mechanisms explaining accelerated cell aging with psychiatric illness, defining directions (if any) of causality and elucidating possible differences in this association between disorders.
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| 3. |
- Han, Laura K. M., et al.
(författare)
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Accelerating research on biological aging and mental health : Current challenges and future directions
- 2019
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 106, s. 293-311
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Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with complex biological changes that can be accelerated, slowed, or even temporarily reversed by biological and non-biological factors. This article focuses on the link between biological aging, psychological stressors, and mental illness. Rather than comprehensively reviewing this rapidly expanding field, we highlight challenges in this area of research and propose potential strategies to accelerate progress in this field. This effort requires the interaction of scientists across disciplines - including biology, psychiatry, psychology, and epidemiology; and across levels of analysis that emphasize different outcome measures - functional capacity, physiological, cellular, and molecular. Dialogues across disciplines and levels of analysis naturally lead to new opportunities for discovery but also to stimulating challenges. Some important challenges consist of 1) establishing the best objective and predictive biological age indicators or combinations of indicators, 2) identifying the basis for inter-individual differences in the rate of biological aging, and 3) examining to what extent interventions can delay, halt or temporarily reverse aging trajectories. Discovering how psychological states influence biological aging, and vice versa, has the potential to create novel and exciting opportunities for healthcare and possibly yield insights into the fundamental mechanisms that drive human aging.
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| 4. |
- Lindqvist, Daniel, et al.
(författare)
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Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging.
- 2015
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Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634. ; 55:May 18, s. 333-364
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Forskningsöversikt (refereegranskat)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.
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