The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology

Abstract

Volumetric reductions in the hippocampus and medial prefrontal cortex (mPFC) are among the most well documented neural abnormalities in major depressive disorder (MDD). Hippocampal and mPFC structural reductions have been specifically tied to MDD illness progression markers, including greater number of major depressive episodes (MDE), longer illness duration, and nonremission/treatment resistance. Chronic stress plays a critical role in the development of hippocampal and mPFC deficits, with some studies suggesting that these deficits occur irrespective of MDE occurrence. However, preclinical and human research also points to other stress-mediated neurotoxic processes, including enhanced inflammation and neurotransmitter disturbances, which may require the presence of a MDE and contribute to further brain structural decline as the illness advances. Specifically, hypothalamic-pituitary-adrenal axis dysfunction, enhanced inflammation and oxidative stress, and neurotransmitter abnormalities (e.g., serotonin, glutamate, gamma-Aminobutyric acid) likely interact to facilitate illness progression in MDD. Congruent with stress-sensitization models of MDD, with each consecutive MDE, it may take lower levels of stress to trigger these neurotoxic pathways leading to more pronounced brain volumetric reductions. Given that stress and MDD have overlapping and distinct influences on neurobiological pathways implicated in hippocampal and mPFC structural decline, further work is needed to clarify which precise mechanisms ultimately contribute to MDD development and maintenance.

Mitochondria could be a potential key mediator linking the intestinal microbiota to depression

“…[19][20][21] Mitochondria have been considered to play key roles in these changes in depression. [19][20][21] Mitochondria have been considered to play key roles in these changes in depression.…”

Early Life Adversity, but not suicide, is associated with less prefrontal cortex gray matter in adulthood

“…Less gray matter volume and cortical thickness are also reported in the frontal cortex in subjects with mood disorders using magnetic resonance imaging by some investigators (see refs (Drevets et al, 1997;Bora and Pantelis, 2011;Belleau et al, 2018)), though not all (Bora and Pantelis, 2011;Gifuni et al, 2016;Rizk et al, 2018). Bora et al (2011) performed a metaanalysis of voxel-based morphometry from 23 studies involving 986 MDD patients and found cortical gray matter volume was reduced in rostral anterior cingulate cortex and dorsolateral and dorsomedial cortex as well as in hippocampus.…”

“…The smaller gray matter volume was related to illness duration leading the authors to conclude that chronic MDD has deleterious but regionally restricted effects on prefrontal cortex (ibid). The volume deficits related to the MDD, and also to stress (see (Belleau et al, 2018). It is not known, however, whether the reduced cortex thickness were attributable to the mood disorder, a suicide component of the psychopathy, or to both.…”

“…Stress and mental illness, including major depressive disorder (MDD), are associated with volumetric loss in medial prefrontal cortex and hippocampus in vivo (see (Belleau et al, 2018) for a recent review). The stress can be recent and associated with the mood disorder or distant and occurring in childhood, and both types of exposures can be associated with smaller brain regional volume.…”

Precise implantation of super-paramagnetic iron oxide (SPIO) nanoparticles in hippocampus with external rotating magnetic field (RMF) produces rapid antidepressent effects in mice

“…Then we designed a protocol to investigate the effects on mice with depression-like behavior. Hippocampus, a region repeatedly implicated in the pathophysiology and depression progression [24], was chosen as our targeted brain region. It shows antidepressive-like effects in CUMS rodent model after a 5-day treatment.…”