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.

Major depressive disorder (MDD) is a debilitating psychiatric mood disorder that affects millions of individuals globally. Our understanding of the biological basis of MDD is poor, and current treatments are ineffective in a significant proportion of cases. This current situation may relate to the dominant rodent animal models of depression, which possess translational limitations due to limited homologies with humans. Therefore, a more homologous primate model of depression is needed to advance investigation into the pathophysiological mechanisms underlying depression and to conduct pre-clinical therapeutic trials. Here, we report two convenient methods – social isolation and social plus visual isolation – which can be applied to construct a non-human primate model of depression in the adult female cynomolgus monkey (Macaca fascicularis). Both social and social plus visual isolation were shown to be effective in inducing depression-like behavior by significantly reducing socially dominant aggressive conflict behavior, communicative behavior, sexual behavior, and parental behavior. The addition of visual isolation produced more profound behavioral changes than social isolation alone by further reducing parental behavior and sexual behavior. Thus, the degree of behavioral pathology may be manipulated by the degree of isolation. These methods can be applied to construct a non-human primate model of depression in order to assess physiological, behavioral, and social phenomena in a controlled laboratory setting.

BackgroundPsychotherapy has demonstrated comparable efficacy to antidepressant medication in the treatment of major depressive disorder. Metabolic alterations in the MDD state and in response to treatment have been detected by functional imaging methods, but the underlying white matter microstructural changes remain unknown. The goal of this study is to apply diffusion tensor imaging techniques to investigate psychotherapy-specific responses in the white matter.MethodsTwenty-one of forty-five outpatients diagnosed with major depression underwent diffusion tensor imaging before and after a four-week course of guided imagery psychotherapy. We compared fractional anisotropy in depressed patients (n = 21) with healthy controls (n = 22), and before-after treatment, using whole brain voxel-wise analysis.ResultsPost-treatment, depressed subjects showed a significant reduction in the 17-item Hamilton Depression Rating Scale. As compared to healthy controls, depressed subjects demonstrated significantly increased fractional anisotropy in the right thalamus. Psychopathological changes did not recover post-treatment, but a novel region of increased fractional anisotropy was discovered in the frontal lobe.ConclusionsAt an early stage of psychotherapy, higher fractional anisotropy was detected in the frontal emotional regulation-associated region. This finding reveals that psychotherapy may induce white matter changes in the frontal lobe. This remodeling of frontal connections within mood regulation networks positively contributes to the “top-down” mechanism of psychotherapy.

In recent years, an increasing number of university students are found to be at high risk of depression. Through a large scale depression screening, this paper finds that around 6.5% of the university postgraduate students in China experience depression. We then investigate whether the gait patterns of these individuals have already changed as depression is suggested to associate with gait abnormality. Significant differences are found in several spatiotemporal, kinematic and postural gait parameters such as walking speed, stride length, head movement, vertical head posture, arm swing, and body sway, between the depressed and non-depressed groups. Applying these features to classifiers with different machine learning algorithms, we examine whether natural gait analysis may serve as a convenient and objective tool to assist in depression recognition. The results show that when using a random forest classifier, the two groups can be classified automatically with a maximum accuracy of 91.58%. Furthermore, a reasonable accuracy can already be achieved by using parameters from the upper body alone, indicating that upper body postures and movements can effectively contribute to depression analysis.

Behavioral studies in non-human primates have become ideal models for further investigations into advanced cognitive function in humans. To date, there is no systematic ethogram of the cynomolgus monkey (Macaca fascicularis) in a free enclosure. In a field observation of 6012 subjects, 107 distinct behaviors of M. fascicularis were preliminarily described. 83 of these behaviors were then independently validated through a randomized cohort and classified into 12 behavioral categories. 53 of these behaviors were then selected to accurately reflect the daily mundane activity of the species in a free enclosure. These findings systematically document the behavior of M. fascicularis in a free enclosure for use in further investigations.

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