Cellular aging in depression: Permanent imprint or reversible process?

Verhoeven, Josine E.; Révész, Dóra; Wolkowitz, Owen M.; Penninx, Brenda W. J. H.

doi:10.1002/bies.201400068

Cited by 43 publications

(28 citation statements)

References 122 publications

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“…In the currently depressed subjects, LTL was inversely associated with severity of depression and with the duration of depression over the preceding four years (although longer-term depressive history was not available), suggesting a “dose-response” relationship (see below in sections 2 and 3). The lack of difference in LTL between active and remitted depressed subjects suggested to the authors that MDD episodes leave a lasting “imprint” on LTL (Verhoeven et al, 2014a; Verhoeven et al, 2014b). However, it is not possible to rule out the possibility that LTL is already short before the first depressive episode, perhaps even representing a risk factor.…”

Section: Telomere Length In Psychiatric Illnessesmentioning

confidence: 99%

“…While few pharmacologic studies have examined this, several behavioral and psychological intervention studies in non-psychiatric populations have examined the effects on PBMC basal TA or LTL of interventions ranging from intensive lifestyle modification, mindful eating, mindfulness-based stress reduction and various types of meditation (see Verhoeven et al 2014b for an overview), although it is unknown if these results would generalize to psychiatric populations. Further, these studies have often been non-randomized and not adequately controlled.…”

Section: Is Cellular Aging Preventable or Reversible?mentioning

confidence: 99%

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Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Lindqvist

Epel

Mellon³

et al. 2015

Neuroscience & Biobehavioral Reviews

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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 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DISCLOSURESJL is a consultant to Telomere Diagnostics Inc., formerly Telome Health, and owns stock in the company. The company had no role in this research or in writing this review. The remaining authors report no current disclosures or conflicts of interest. HHS Public Access

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Section: Telomere Length In Psychiatric Illnessesmentioning

confidence: 99%

Section: Is Cellular Aging Preventable or Reversible?mentioning

confidence: 99%

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Lindqvist

Epel

Mellon³

et al. 2015

Neuroscience & Biobehavioral Reviews

Self Cite

271

231

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“…Depressed, anxious, fatigued and Type D patients show elevated cortisol levels [44][45][46][47], suggesting that HPA-axis dysregulation is a possible mechanism. Likewise, anxiety and depression are related to shorter telomere length [48][49][50], a biomarker of cellular aging, which is in turn involved in the pathogenesis of CVD [51].…”

Section: Behavioral and Pathophysiological Mechanisms Involved In Psymentioning

confidence: 99%

Cardiovascular co-morbidity in cancer patients: the role of psychological distress

et al. 2016

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Due to aging of the population and cardiotoxic cancer treatment, there is an increasing group of patients with cancer and co-morbid cardiovascular disease (CVD). In order to find a balance between the risk of undertreating the malignancy on the one hand and inducing CVD on the other hand, CVD risk stratification at the time of cancer diagnosis and knowledge on the pathway for developing incident CVD in cancer patients is vital. In this paper, we propose an adapted multiple-hit hypothesis for developing CVD in cancer patients describing that patients with cancer are exposed to a series of sequential or concurrent events that together make them more vulnerable to reduced cardiovascular reserves, development of incident CVD and ultimately death. We highlight the possible impact of psychological distress secondary to a cancer diagnosis and/or treatment, which in turn may increase the risk of incident CVD in patients diagnosed with cancer. Furthermore, we discuss potential behavioral and pathophysiological mechanisms underlying the link between psychological distress and the pathophysiology of incident CVD. In addition, key unanswered questions for future research are posed. In the future, researching the adapted multiple-hit hypothesis for developing CVD among cancer patients will hopefully advance the care of cancer patients by finding some of the missing pieces of the puzzle. To do so, we need to focus on minimizing cardiovascular risk and promoting cardiovascular health in cancer patients by addressing the knowledge gaps formulated in this paper.Keywords: Cancer, Survivors, Cardiovascular, Psychological distress, Mechanisms Cardiovascular co-morbidity in cancer patientsDue to aging of the population, there is an increasing number of patients with cancer and co-morbid cardiovascular disease (CVD). Additionally, cancer patients may develop incident CVD as a result of the cardiotoxicity of cancer treatment. Fortunately, there has been increasing awareness of co-morbid CVD in cancer patients. In 2009, the International CardiOncology Society (ICOS) was established [1]. ICOS advocates a multi-disciplinary effort to combat CVD in cancer patients by both training oncologists and cardiologists and conducting multidisciplinary research. In 2014, during the international colloquium on cardio-oncology, ICOS stressed the importance of finding a balance between the risk of undertreating the malignancy on the one hand and inducing CVD by overtreating on the other hand [2]. In order to accomplish this goal, they emphasize the importance of CVD risk stratification at the time of cancer diagnosis. Recommendations based on consensus have also been published to target the vulnerable cancer patient population, emphasizing the importance of a thorough cardiac evaluation, including the assessment of risk factors, prior to formulating a cancer treatment plan [3].Adapted multiple-hit hypothesis: the impact of psychological distress Important in CVD risk stratification is knowledge of the pathway for developing CVD in cancer patie...

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“…Although the molecular and cellular mechanisms underlying MDD are not fully known, changes in cellular aging, indexed by shortened leukocyte telomeres, may be a novel aspect of MDD pathophysiology [2, 3]. …”

Section: Introductionmentioning

confidence: 99%

Leukocyte Telomere Length Predicts SSRI Response in Major Depressive Disorder: A Preliminary Report

Hough

Bersani

Mellon³

et al. 2016

Complex Psychiatry

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Short leukocyte telomere length (LTL) may be associated with several psychiatric disorders, including major depressive disorder (MDD). Short LTL has previously been associated with poor response to psychiatric medications in bipolar disorder and schizophrenia, but no studies have prospectively assessed the relationship of LTL to selective serotonin reuptake inhibitor (SSRI) response in MDD. We assessed pre-treatment LTL, depression severity [using the Hamilton Depression Rating Scale (HDRS)], and self-reported positive and negative affect in 27 healthy, unmedicated adults with MDD. The subjects then underwent open-label treatment with an SSRI antidepressant for 8 weeks, after which clinical ratings were repeated. The analyses were corrected for age, sex, and body mass index. ‘Non-responders' to treatment (HDRS improvement <50%) had significantly shorter pre-treatment LTL than ‘responders' (p = 0.037). Further, shorter pre-treatment LTL was associated with less improvement in negative affect (p < 0.010) but not with changes in positive affect (p = 0.356). This preliminary study is the first to assess the relationship between LTL and response to SSRIs in MDD and among the first to prospectively assess its relationship to treatment outcome in any psychiatric illness. Our data suggest that short LTL may serve as a vulnerability index of poorer response to SSRI treatment, but this needs examination in larger samples.

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Cellular aging in depression: Permanent imprint or reversible process?

Cited by 43 publications

References 122 publications

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Cardiovascular co-morbidity in cancer patients: the role of psychological distress

Leukocyte Telomere Length Predicts SSRI Response in Major Depressive Disorder: A Preliminary Report

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