Neuroplasticity in mood disorders

Abstract

Neuroimaging and neuropathological studies of major depressive disorder (MDD) and bipolar disorder (BD) have identified abnormalities of brain structure in areas of the prefrontal cortex, amygdala, striatum, hippocampus, parahippocampal gyrus, and raphe nucleus. These structural imaging abnormalities persist across illness episodes, and preliminary evidence suggests they may in some cases arise prior to the onset of depressive episodes in subjects at high familial risk for MDD. In other cases, the magnitude of abnormality is reportedly correlated with time spent depressed. Postmortem histopathological studies of these regions have shown abnormal reductions of synaptic markers and glial cells, and, in rare cases, reductions in neurons in MDD and BD. Many of the regions affected by these structural abnormalities show increased glucose metabolism during depressive episodes. Because the glucose metabolic signal is dominated by glutamatergic transmission, these data support other evidence that excitatory amino acid transmission is elevated in limbic-cortical-striatal-pallidal-thalamic circuits during depression. Some of the subject samples in which these metabolic abnormalities have been demonstrated were also shown to manifest abnormally elevated stressed plasma cortisol levels. The co-occurrence of increased glutamatergic transmission and Cortisol hypersecretion raises the possibility that the gray matter volumetric reductions in these depressed subjects are partly accounted for by processes homologous to the dendritic atrophy induced by chronic stress in adult rodents, which depends upon interactions between elevated glucocorticoid secretion and N-meihyl-D-aspartate (NMDA)-glutamate receptor stimulation. Some mood-stabilizing and antidepressant drugs that exert neurotrophic effects in rodents appear to reverse or attenuate the gray matter volume abnormalities in humans with mood disorders. These neurotrophic effects may be integrally related to the therapeutic effects of such agents, because the regions affected by structural abnormalities in mood disorders are known to play major roles in modulating the endocrine, autonomic, behavioral, and emotional experiential responses to stressors.

Translational studies of goal-directed action as a framework for classifying deficits across psychiatric disorders

“…The difficulties depressed individuals have with learning and performance of goal-directed action correspond with abnormalities in learning and choice related brain regions. Gray matter volumetric studies and postmortem examinations have show neuronal size reductions relative to controls in the OFC (Cotter et al, 2005 ; Drevets and Price, 2008 ), left ACC (Drevets et al, 1997 ; Coryell et al, 2005 ), dlPFC (Drevets, 2004 ), caudate and NAc (Baumann et al, 1999 ). Moreover, symptoms of anhedonia, depression severity and probability of suicide have all been associated with reduced caudate volume (Pizzagalli et al, 2008 ) and caudate activity (Forbes et al, 2009 ).…”

Sex differences in the association between basal serum cortisol concentrations and cortical thickness

“…In the present study, data of 1441 men and 1153 women of the population-based Study of Health in Pomerania (SHIP) was used to investigate associations between basal serum cortisol concentrations and cortical thickness. According to previous reports, we expected an inverse association between serum cortisol concentrations and cortical thickness ( Alonso, 2000 ; Simmons et al, 2000 ; Patil et al, 2007 ; Gnjidić et al, 2008 ; Drevets, 2004 ; Liu et al, 2015 ; Lebedeva et al, 2018 ). Integrating the well-described interaction of the HPA and HPG axis ( Gray et al, 2017 ; Bourke et al, 2012 ; Hertel et al, 2017 ; Baker and Driver, 2007 ; Cumming et al, 1983 ), we further expected sex differences in these cortisol-cortical thickness associations.…”

“…In humans, increased cortisol concentrations in Cushing's syndrome patients were associated with global brain atrophy ( Simmons et al, 2000 ; Patil et al, 2007 ; Gnjidić et al, 2008 ). Similarly, a regional reduction of gray matter volume and cortical thickness in depressed patients was related to higher blood and saliva cortisol concentrations ( Drevets, 2004 ; Liu et al, 2015 ; Lebedeva et al, 2018 ). Besides, reduced cortical thickness has been associated with childhood maltreatment ( Kelly et al, 2013 ; Wang et al, 2016 ).…”

“…Previous studies investigating associations between cortisol concentrations and brain alterations were mostly based on animal models or patient samples ( Alonso, 2000 ; Simmons et al, 2000 ; Patil et al, 2007 ; Gnjidić et al, 2008 ; Drevets, 2004 ; Liu et al, 2015 ; Lebedeva et al, 2018 ; Gray et al, 2017 ). Further, particularly integrating potential sex differences, previous studies majorly focused on associations between cortisol concentrations and volumes of subcortical structures neglecting cortical structures ( Gray et al, 2017 ).…”

Acute stress‐induced neuronal plasticity in the corticoid complex of 15‐day‐old chick, Gallus domesticus

“…The whole-brain possess a remarkable ability to undergo functionally relevant adaptations following external and/or internal stimuli like stress and is generally referred to as neural plasticity (Chattarji et al, 2015;Drevets, 2004;McEwen, 2007). The stress induces structural remodeling of neuronal architecture for the adaptation of stressor commonly by strengthening the synaptic transmission (Krugers et al, 2010) as failing to do so may contribute to the onset and recurrence of mood disorders like depression and anxiety (McEwen, 2007;Southwick & Charney, 2012).…”