Reconsidering Animal Models of Major Depressive Disorder in the Elderly.

Shigenobu Toda,Ziqiao Lin,Yoshio Minabe,Hirotaka Watanabe,Tatsuya Nagasawa,Yoshio Iguchi,Hiromi Nishikawa

doi:10.3389/fnagi.2016.00188

Abstract

Major depressive disorder (MDD) is a common psychiatric illness with high morbidity that poses a huge burden to healthcare systems worldwide. According to the World Health Organization, the lifetime prevalence of MDD is approximately 3–17% globally (Richards, 2011). However, after major, but limited, success with selective serotonin reuptake inhibitors (SSRIs) or serotonin–noradrenaline reuptake inhibitors, few promising therapeutic approaches have been developed from preclinical studies using current animal models of MDD, despite intensive research involving laborious methods and substantial costs. Traditionally, most research using rodent models of MDD has been conducted using relatively young adult animals, aged approximately 8 weeks, to avoid any involvement of aging-related biological factors. The major rationale of this strategy is based on epidemiological findings that the occurrence of MDD displays a robust peak in young adults rather than in the elderly (Jorm, 2000; Copeland et al., 2004; Blazer and Hybels, 2005). Further, the elderly may have aging-related factors rendering this group an inappropriate model of “genuine” MDD. A critical question is whether this strategy is indeed appropriate. Despite the consistent findings of a lower lifetime prevalence rate of MDD in the elderly than in young adults, there remain persistent doubts regarding the underdiagnosis of MDD in the elderly (Hoertel et al., 2013). It has been heavily argued that patients diagnosed with MDD in youth will often be rediagnosed with a bipolar disorder (Lish et al., 1994; Leonpacher et al., 2015). Thus, a considerable number of cases of MDD in young adults may be misdiagnosed. In addition, MDD in the elderly has distinct biological/environmental backgrounds and consequences compared with that in young adults. In this opinion article, we primarily shed light on the significance of MDD in the elderly (known as geriatric MDD or late-onset depression) and problems associated with the methodology of preclinical studies undertaken to investigate the characteristics and treatment of this disorder.

Highlights

Major depressive disorder (MDD) is a common psychiatric illness with high morbidity that poses a huge burden to healthcare systems worldwide
After major, but limited, success with selective serotonin reuptake inhibitors (SSRIs) or serotonin–noradrenaline reuptake inhibitors, few promising therapeutic approaches have been developed from preclinical studies using current animal models of MDD, despite intensive research involving laborious methods and substantial costs
The major rationale of this strategy is based on epidemiological findings that the occurrence of MDD displays a robust peak in young adults rather than in the elderly (Jorm, 2000; Copeland et al, 2004; Blazer and Hybels, 2005)

Summary

Reconsidering Animal Models of Major Depressive Disorder in the Elderly

Shigenobu Toda 1, 2, 3*, Yoshio Iguchi 4, Ziqiao Lin 1, Hiromi Nishikawa 1, Tatsuya Nagasawa 1, 3, Hirotaka Watanabe 5 and Yoshio Minabe 1, 2, 3. Edited by: Rodrigo Orlando Kuljiš, The University of Miami Leonard M.

INTRODUCTION

INFLUENCES OF AGING ON PHYSIOLOGICAL FUNCTIONS

CAUSAL RELATIONSHIP BETWEEN MDD AND DEMENTIA IN THE ELDERLY

FURTHER PROMISING RELATIONSHIPS BETWEEN STRESS AND DEMENTIA

OTHER FACTORS THAT EXAGGERATE MDD IN THE ELDERLY