103. Fatigue in adolescent girls: A psychoneuroimmunological approach Cobi J. Heijnen *, Maike te... more 103. Fatigue in adolescent girls: A psychoneuroimmunological approach Cobi J. Heijnen *, Maike ter Wolbeek , Lorenz J.P. van Doornen , Annemieke Kavelaars a a Laboratory of Psychoneuroimmunology, University Medical Center-Utrecht, Lundlaan 6, Utrecht, The Netherlands b Department of Health Psychology, Utrecht University, Utrecht, The Netherlands * Corresponding author. E-mail: c.heijnen@umcutrecht.nl
Short leukocyte telomere length (LTL) may be associated with several psychiatric disorders, inclu... more 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.
Abstract Depression is associated with early mortality and with an increased risk of developing p... more Abstract Depression is associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, depression may be associated with aspects of 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 depression, perhaps in proportion to exposure to the depressive illnesses, although conflicting data exist. Although telomerase has been less well-characterized, a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this chapter, studies on LTL and telomerase activity in depression are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in depressive disorders could lead to reconceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets.
Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnos... more Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using...
103. Fatigue in adolescent girls: A psychoneuroimmunological approach Cobi J. Heijnen *, Maike te... more 103. Fatigue in adolescent girls: A psychoneuroimmunological approach Cobi J. Heijnen *, Maike ter Wolbeek , Lorenz J.P. van Doornen , Annemieke Kavelaars a a Laboratory of Psychoneuroimmunology, University Medical Center-Utrecht, Lundlaan 6, Utrecht, The Netherlands b Department of Health Psychology, Utrecht University, Utrecht, The Netherlands * Corresponding author. E-mail: c.heijnen@umcutrecht.nl
Short leukocyte telomere length (LTL) may be associated with several psychiatric disorders, inclu... more 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.
Abstract Depression is associated with early mortality and with an increased risk of developing p... more Abstract Depression is associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, depression may be associated with aspects of 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 depression, perhaps in proportion to exposure to the depressive illnesses, although conflicting data exist. Although telomerase has been less well-characterized, a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this chapter, studies on LTL and telomerase activity in depression are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in depressive disorders could lead to reconceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets.
Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnos... more Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using...
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