Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression

Neural Plasticity, Dec 2015

Anxiety disorders (AnxDs) are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Aβ accumulation, and immune-inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://downloads.hindawi.com/journals/np/2016/8457612.pdf

Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression

Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression Giampaolo Perna,1,2,3 Giuseppe Iannone,1 Alessandra Alciati,1 and Daniela Caldirola1 1Department of Clinical Neurosciences, Hermanas Hospitalarias, FoRiPsi, Villa San Benedetto Menni, Albese con Cassano, 22032 Como, Italy 2Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200 MD Maastricht, Netherlands 3Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, Miami University, Miami, FL 33136, USA Received 6 August 2015; Revised 5 October 2015; Accepted 8 October 2015 Academic Editor: James M. Wyss Copyright © 2016 Giampaolo Perna et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Anxiety disorders (AnxDs) are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Aβ accumulation, and immune-inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed. 1. Introduction Anxiety disorders (AnxDs) are highly prevalent across the lifespan in the general population. Pooled 1-year and lifetime prevalence have been estimated at around 11% and 17%, respectively [1]. Different AnxDs are more prevalent at specific lifespan stages. Phobias predominate in childhood, panic disorder (PD) predominates in adulthood, and generalized anxiety disorder (GAD) and agoraphobia (AG) predominate in adulthood and older age. AnxDs can also have a late onset, with an incidence of 3-4% after 55–60 years of age [2–4]. AnxDs are chronic and stressful conditions that can negatively affect quality of life, somatic health, and cognitive performance. Several studies documented that anxiety is a risk factor for many age-related medical conditions, such as coronary heart disease, diabetes, and disability, as well as for global mortality [5–7]. Recent findings showed an association between AnxDs or anxiety symptoms and reduced verbal memory, language, and executive functions in older individuals without dementia [8–11]. An emerging perspective suggested that in people with AnxDs decreased somatic health or cognition may partly result from accelerated cellular aging and neuroprogression. Neuroprogression is pathological reorganization of the central nervous system (CNS), along the course of severe mental disorders, leading to cerebral structural changes and functional alterations. It is a combination of increased neurodegeneration, neuronal apoptosis or neurotoxic susceptibility, and lowered neuroplasticity [12]. Neuroplasticity refers to the ability of the brain to modify itself in response to environmental demands and it plays an important role in optimizing brain functionality. It encompasses neurogenesis, structural and functional brain reorganization, cellular and molecular changes, and cognitive plasticity [13]. These processes occur throughout the lifespan in response to a wide array of genetic and environmental factors. Neuroplasticity is downregulated in adulthood and old age and its impairment can negatively impact successful aging [14] and cognitive performance [15]. Neuroprogression has been extensively investigated in major depressive disorder (MDD)/bipolar disorder (BD) and several potential mechanisms of neuroprogression have been proposed, including immune-inflammatory and oxidative/nitrosative stress with its concomitants and sequels, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and immune system or neurotransmit (...truncated)


This is a preview of a remote PDF: http://downloads.hindawi.com/journals/np/2016/8457612.pdf

Giampaolo Perna, Giuseppe Iannone, Alessandra Alciati, Daniela Caldirola. Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression, Neural Plasticity, 2015, 2016, DOI: 10.1155/2016/8457612