Macaques Exhibit a Naturally-Occurring Depression Similar to Humans

Abstract

Rodent models have dominated preclinical investigations into the mechanisms of depression. However, these models-which rely on subjecting individual rodents to physical stressors - do not realistically resemble the etiopathological development of depression, which occurs naturally in a social context. A non-human primate model that better reflects the social ethological aspects of depression would be more advantageous to investigating pathophysiological mechanisms and developing antidepressant therapeutics. Here, we describe and model a naturally-occurring depressive state in a non-human primate species, the cynomolgus monkey (Macaca fascicularis), in a realistic social ethological context and associate the depressed behavioral phenotype with significant serum metabolic perturbations. One to two subjects per stable social colony (17–22 subjects) manifested a depressive phenotype that may be attributed to psychosocial stress. In accordance with rodent and human studies, the serum metabolic phenotype of depressed and healthy subjects significantly differed, supporting the model's face validity. However, application of the fast-acting antidepressant ketamine failed to demonstrate predictive validity. This study proposes a non-human primate depression model in a realistic social ethological context that can better approximate the psychosocial stressors underlying depression.

On the depressive nature of the “burnout syndrome”: A clarification

“…Burnout is thought to result from unresolvable stress. As long evidenced by research conducted in psychiatry, behavioral psychology, and neurobiology, depressive symptoms constitute basic responses to unresolvable stress in homosapiens, as in many other species [4–8]. Unmanageable adversity, in any life domain valued by the individual (e.g., work), is fundamentally depressogenic [1,5].…”

Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study

“…Our group has focused on MDD over a decade, and has previously conducted proteomics and non-targeted metabolomics studies on rodent models of depression, on non-human primate (Macaca fascfeiicularis) model, and on patients with MDD 9 – 15 . Previous studies have showed that perturbations in central and peripheral neurotransmitters are a hallmark of MDD.…”

<p>Metabonomics reveals peripheral and central short-chain fatty acid and amino acid dysfunction in a naturally occurring depressive model of macaques</p>

“…Here, a non-targeted metabolomics approach based on gas chromatography–mass spectrometry (GC–MS) was used to identify differentially expressed metabolites between NOD and control macaques based on a previous study 16. To systematically analyze the role of differentially expressed metabolites, the differential metabolites identified in this study were compared with those reported in our published findings 16. Some key metabolites were detected both in the and CSF, which may provide an evidence to understand peripheral and central interactions.…”