Accelerating research on biological aging and mental health: Current challenges and future directions

Han, Laura K.M.; Verhoeven, Josine E.; Tyrka, Audrey R.; Penninx, Brenda W.J.H.; Wolkowitz, Owen M.; Månsson, Kristoffer; Lindqvist, Daniel; Boks, Marco P.; Révész, Dóra; Mellon, Synthia H.; Picard, Martin

doi:10.1016/j.psyneuen.2019.04.004

Cited by 66 publications

(50 citation statements)

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“…In addition, it remains to be elucidated how adaptable brain-PAD is in response to pharmacotherapy. Randomized controlled intervention studies are needed to develop an understanding of how reversible or modifiable brain aging is in response to pharmacological and nonpharmacological strategies (e.g., psychological, exercise, and/or nutritional interventions), as seen in other biological age indicators [21,39]. comparison of these studies.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence from studies suggests that, at the group level, MDD patients follow advanced aging trajectories, as their functional (e.g., walking speed, handgrip strength) [16] and biological state (e.g. telomeres, epigenetics, mitochondria) [17][18][19][20] reflects what is normally expected at an older age (i.e., biological age "outpaces" chronological age) [21]. It is important to examine whether biological aging findings in depression can be confirmed in a large heterogeneous dataset consisting of many independent samples worldwide, based on commonly derived gray matter measures.…”

Section: Introductionmentioning

confidence: 99%

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Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

et al. 2020

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Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

et al. 2020

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“…Commonly used indices are based on telomere length, DNA methylation patterns (epigenetic age), variation in transcription (transcriptomic age) as well as alterations in the metabolome (metabolomic age) and in the proteome (proteomic age) (see Han et al. 2 , Xia et al 3 and Jylhava et al 4 for recent reviews). Biological clocks are computed as the residuals of regressing biological age on chronological age: a positive value means that the biological age is larger than the chronological age.…”

Section: Introductionmentioning

confidence: 99%

An integrative study of five biological clocks in somatic and mental health

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Verhoeven

Han

et al. 2020

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1 5 15 20 ABSTRACT Biological clocks have been developed at different molecular levels and were found to be more advanced in the presence of somatic illnesses and mental disorders. However, it is unclear whether different biological clocks reflect similar aging processes and determinants. In ~3000 subjects, we examined whether 5 biological clocks (telomere length, epigenetic, transcriptomic, proteomic and metabolomic clocks) were interrelated and associated to somatic and mental health determinants.Correlations between biological clocks were small (all r<0.2), indicating little overlap. The most consistent associations with the advanced biological clocks were found for male sex, higher BMI, metabolic syndrome, smoking and depression. As compared to the individual clocks, a composite index of all five clocks showed most pronounced associations with health determinants. The large effect sizes of the composite index and the low correlation between biological clocks, indicate that one's biological age is best reflected by combining aging measures from multiple cellular levels. 2 30 35 40 45

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“…However, another study found decreased telomerase activity in a chronically stressed sample [24], leaving it unclear whether increased activity of the enzyme is a sign of improved health or rather a compensatory mechanism. The extent to which depression and anxiety treatment impacts the telomere/ telomerase system has not been extensively examined [25].…”

Section: Introductionmentioning

confidence: 99%

The impact of depression and anxiety treatment on biological aging and metabolic stress: study protocol of the Mood treatment with antidepressants or running (MOTAR) study

et al. 2019

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BackgroundDepressive and anxiety disorders have shown to be associated to premature or advanced biological aging and consequently to adversely impact somatic health. Treatments with antidepressant medication or running therapy are both found to be effective for many but not all patients with mood and anxiety disorders. These interventions may, however, work through different pathophysiological mechanisms and could differ in their impact on biological aging and somatic health. This study protocol describes the design of an unique intervention study that examines whether both treatments are similarly effective in reducing or reversing biological aging (primary outcome), psychiatric status, metabolic stress and neurobiological indicators (secondary outcomes).MethodsThe MOod Treatment with Antidepressants or Running (MOTAR) study will recruit a total of 160 patients with a current major depressive and/or anxiety disorder in a mental health care setting. Patients will receive a 16-week treatment with either antidepressant medication or running therapy (3 times/week). Patients will undergo the treatment of their preference and a subsample will be randomized (1:1) to overcome preference bias. An additional no-disease-no-treatment group of 60 healthy controls without lifetime psychopathology, will be included as comparison group for primary and secondary outcomes at baseline. Assessments are done at week 0 for patients and controls, and at week 16 and week 52 for patients only, including written questionnaires, a psychiatric and medical examination, blood, urine and saliva collection and a cycle ergometer test, to gather information about biological aging (telomere length and telomerase activity), mental health (depression and anxiety disorder characteristics), general fitness, metabolic stress-related biomarkers (inflammation, metabolic syndrome, cortisol) and genetic determinants. In addition, neurobiological alterations in brain processes will be assessed using structural and functional Magnetic Resonance Imaging (MRI) in a subsample of at least 25 patients per treatment arm and in all controls.DiscussionThis intervention study aims to provide a better understanding of the impact of antidepressant medication and running therapy on biological aging, metabolic stress and neurobiological indicators in patients with depressive and anxiety disorders in order to guide a more personalized medicine treatment.Trial registrationTrialregister.nl Number of identification: NTR3460, May 2012.

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Accelerating research on biological aging and mental health: Current challenges and future directions

Cited by 66 publications

References 265 publications

Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

An integrative study of five biological clocks in somatic and mental health

The impact of depression and anxiety treatment on biological aging and metabolic stress: study protocol of the Mood treatment with antidepressants or running (MOTAR) study

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