Abstract
Depression is a debilitating disorder causing significant societal and personal suffering. Improvements in identification of major depressive disorder (MDD) and its treatment are essential to reduce its toll. Recent developments in rodent models of MDD and neuroimaging of humans suffering from the disorder provide avenues through which gains can be made towards reducing its burden. In this review, new findings, integrating across rodent models and human imaging are highlighted that have yielded new insights towards a basic understanding of the disorder. In particular, this review focuses on cortical-subcortical interactions underlying the pathophysiology of MDD. In particular, evidence is accruing that dysfunction in prefrontal-subcortical circuits including the amygdala, ventral striatum (VS), hippocampus and dorsal raphe nucleus (DRN) are associated with MDD status.
Highlights
According to the most recent Global Burden of Disease Study sponsored by the World Health Organization, Harvard School of Public Health, and the World Bank, major depressive disorder (MDD) is the second leading cause of disability worldwide (Moussavi et al, 2007; World Health Organization, 2009)
It is the medial prefrontal cortex that has direct, monsynaptic connections to the ventral striatum (VS) and amygdala and is the area most typically examined in animal studies
The smaller rodent acts in a similar helpless way and a depression-like phenotype characterized by anhedonia and social avoidance behaviors is engendered (Ménard et al, 2015)
Summary
According to the most recent Global Burden of Disease Study sponsored by the World Health Organization, Harvard School of Public Health, and the World Bank, major depressive disorder (MDD) is the second leading cause of disability worldwide (Moussavi et al, 2007; World Health Organization, 2009). It is well established that medically ill patients with comorbid MDD experience significantly worse clinical courses for their medical illnesses, i.e., cancer, heart and kidney disease, etc., despite receiving standard medical treatment (Mavrides and Nemeroff, 2015) These findings, taken together with the more than 40,000 suicides in the USA (and one million worldwide), demonstrate the massive public health problem represented by MDD. The PFC is well-known to have subregions, and these subregions have differential roles in cognition (Badre, 2008), emotional regulation (Ochsner et al, 2012) and MDD (Koenigs and Grafman, 2009) It is the medial prefrontal cortex (mPFC) that has direct, monsynaptic connections to the VS and amygdala and is the area most typically examined in animal studies. Some imaging studies have found significant effects of connectivity between the DLPFC and subcortical structures, these effects are likely mediated through an intermediary region as there are minimal direct projections between the DLPFC and subcortex
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