Mechanisms Underlying Neurocognitive Dysfunctions in Recurrent Major Depression

Abstract

Recent work shows that depression is intimately associated with changes in cognitive functioning, including memory, attention, verbal fluency, and other aspects of higher-order cognitive processing. Changes in cognitive functioning are more likely to occur when depressive episodes are recurrent and to abate to some degree during periods of remission. However, with accumulating frequency and duration of depressive episodes, cognitive deficits can become enduring, being evident even when mood improves. Such changes in cognitive functioning give depression links to mild cognitive impairment and thereby with neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, schizophrenia, and multiple sclerosis. Depression may then be conceptualized on a dimension of depression – mild cognitive impairment – dementia. The biological underpinnings of depression have substantial overlaps with those of neurodegenerative conditions, including reduced neurogenesis, increased apoptosis, reactive oxygen species, tryptophan catabolites, autoimmunity, and immune-inflammatory processes, as well as decreased antioxidant defenses. These evolving changes over the course of depressive episodes drive the association of depression with neurodegenerative conditions. As such, the changes in cognitive functioning in depression have important consequences for the treatment of depression and in reconceptualizing the role of depression in wider neuroprogressive conditions. Here we review the data on changes in cognitive functioning in recurrent major depression and their association with other central conditions.

Resveratrol counteracts lipopolysaccharide-induced depressive-like behaviorsviaenhanced hippocampal neurogenesis

“…Adult hippocampal neurogenesis in the subgranular zone (SGZ) of the DG contributes to mood regulation [ 4 ]. Brain imaging and postmortem studies of patients suggest that reduced DG size may be related to decreased neurogenesis and mature neuronal cell loss [ 5 ].…”

Expression and Activity of Metalloproteinases in Depression

“…Significant participation of matrix metalloproteinases (MMPs) in the development and modulation of the inflammatory process has been reported in pathological processes, such as Alzheimer disease (AD), cancers, and cardiovascular diseases, brain and heart strokes, and multiple sclerosis [ 13 – 18 ]. Inflammatory diseases affect neurodegenerative processes of the central nervous system (CNS) [ 19 , 20 ] by influencing damage to the blood-brain barrier (BBB) [ 19 ]. Recent reports show that MMPs play an important role in pathological processes in the CNS [ 21 ].…”

Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

“…The proportion of MDD patients that encountered recurrence episodes is estimated at 50%–60% [ 55 ]. Cognitive symptoms in recurrent depressive disorder (rDD) represent the largest range of cognitive impairments during the MDD pathology with decrements in memory, learning, attention, spatial visualization, visual-motor coordination, verbal fluency and memory, psychomotor retardation and most of the executive functions (planning, problem solving, behavioral inhibition, mental flexibility) [ 56 , 57 , 58 ]. A way to examine the degree of cognitive deficits in recurrent depressive disorders is to gather studies that compare first-MDD episode cognitive symptoms to recurrent depressive cognitive symptoms.…”