disruptions in connectivity across distributed neural networks are common features of stress - related neuropsychiatric conditions , and understanding how they arise may yield new insights into mechanisms of resilience and vulnerability .
stress has potent effects on apical dendrites and postsynaptic dendritic spines in multiple brain regions . in the hippocampus , which plays an important negative feedback role in hpa axis regulation ,
chronic stress causes atrophy of apical dendrites in ca1 and ca3 pyramidal cells and a decrease in the density of postsynaptic dendritic spines ( jacobson and sapolsky , 1991 , magarios and mcewen , 1995a , magarios and mcewen , 1995b , magarios et  al . , 1996 ,
, 1997 , sousa et  al . , 2000 , vyas et  al . ,
other studies have identified associated behavioral deficits in spatial learning and memory tasks such as the radial arm and y mazes ( luine et  al . , 1994 , conrad et  al . , 1996 ,
in contrast , in the amygdala , which up - regulates hpa axis activity , chronic stress causes hypertrophy of dendritic arbors , accompanied by a facilitation of aversive learning and heightened fear and anxiety ( vyas et  al .
importantly , analogous effects have been observed in parallel rodent and human neuroimaging studies of the prefrontal cortex ( fig .  1 ) .
many of these studies have focused on the dorsolateral prefrontal cortex in humans , and the medial prefrontal cortex in rodents , as these regions share important functional and neuroanatomical similarities ( ongur and price , 2000 , dalley et  al . ,
2004 ) , although it should be noted that rodents do have a dorsal prefrontal cortex , which may contribute to associated cognitive functions ( lai et  al . , 2012 ) . in rats , pyramidal cells in layer ii / iii of the medial pfc
show a pattern of structural changes similar to what has been observed in the hippocampus : retraction of apical dendritic branches and reduced spine density after repeated stress exposure ( cook and wellman , 2004 , radley et  al .
these changes were associated with specific deficits in an extradimensional attentional set shifting task that correlated with individual differences in the degree of dendritic atrophy ( liston et  al . , 2006 ) . in another study , chronic stress caused deficits in spatial working memory that correlated with spine loss on the apical dendrites of prelimbic pyramidal cells ( hains et  al . , 2009 ) .
the apical dendrites of layer ii / iii pyramidal cells are important recipients of long - range corticocortical projections , so apical dendritic atrophy would be expected to impair functional connectivity across neuroanatomically distributed brain networks ( dehaene et  al . , 1998 ) .
this is exactly what was observed in a related functional neuroimaging study ( liston et  al . , 2009 ) . here ,
chronically stressed but otherwise healthy human subjects were tested on an attention shifting task during fmri scanning .
they exhibited deficits in fmri measures of functional connectivity between dorsolateral prefrontal cortex and a frontoparietal attention network that were correlated with stress levels and attention shifting impairments .
similar effects were also observed in the medial prefrontal cortex in another human neuroimaging study , in which stressful life events were associated with decreased gray matter volume in the medial prefrontal , anterior cingulate , and subgenual cingulate cortex ( ansell et  al . , 2012 ) .
thus , chronic stress has been linked to deficits in structural and functional connectivity measures and associated attentional impairments in both rodent models and human neuroimaging studies .
these studies also indicate that connectivity in cortical networks is highly plastic and is often capable of recovering after a change in stress exposure . in rats , four weeks after cessation of the stressor , spine densities fully recovered to unstressed levels ( radley et  al . , 2005 ) .
similarly , when the same human subjects were re - scanned after a month of rest and reduced stress , both functional connectivity deficits and attention shifting impairments normalized and were no different from unstressed control subjects ( liston et  al . ,
the reversibility of these stress effects underscores the striking capacity for resilience that is evident in the healthy brain .
while the healthy human brain demonstrates a remarkable capacity for adaptation and recovery from stressors in daily life , patients with neuropsychiatric disorders often do not . in a recent clinical neuroimaging study
, we found that patients with depression exhibited a similar pattern of functional connectivity deficits between dorsolateral prefrontal cortex and a frontoparietal control network that may contribute to rumination , executive control deficits , and other cognitive symptoms ( liston et  al .
however , in contrast to the study of chronically stressed but otherwise healthy subjects , when depressed patients were re - scanned after five weeks of antidepressant treatment , frontoparietal connectivity deficits persisted ( liston et  al . ,
these results are consistent with the hypothesis that stress - associated changes in connectivity in large - scale brain networks are an important feature of depression and other stress - related neuropsychiatric disorders , and that resilience and vulnerability may be determined in part by individual differences in the capacity for plasticity within these circuits .
understanding the mechanisms by which stress alters connectivity in vulnerable circuits may reveal new avenues for treatment .
undoubtedly , many factors are involved , and some of them have been reviewed elsewhere ( de kloet et  al .
, 2005b , arnsten , 2009 , jols and baram , 2009 , chen et  al . ,
we focus on a factor that has received relatively little attention , namely , endogenous glucocorticoid oscillations and their role in regulating synaptic plasticity .
glucocorticoids are hormones that are released from the adrenal gland in response to signals originating in the pituitary and hypothalamus , which receives projections from distinct circuits for detecting physiological and psychosocial stressors ( herman and cullinan , 1997 , ulrich - lai and herman , 2009 ) ( fig . 
, glucocorticoids serve to mobilize energy resources and facilitate sympathetic nervous system responses to maintain homeostasis and adapt to stress . in the long term , however , prolonged exposure to glucocorticoids in chronic stress states can have maladaptive effects , mediated in part by disruptions in negative feedback mechanisms ( mcewen , 1998 , mcewen , 2003 ) .
glucocorticoid activity also oscillates with diurnal activity rhythms , independent of external stressors ( fig . 
2b ) : glucocorticoid secretion tends to peak in the early morning in diurnal animals ( early evening in nocturnal animals ) , remains relatively elevated for most of the active period of the animal 's day , and becomes relatively suppressed for most of the night . in addition , recent reports ( stavreva et  al .
, 2009 , lightman and conway - campbell , 2010 ) have shown that an ultradian oscillation with a period of 12  h is superimposed on this circadian rhythm and has equally important consequences for glucocorticoid signaling ( reviewed below ) . in previous fixed tissue studies , stress and glucocorticoid effects on dendritic
2006 ) , which would imply that glucocorticoid oscillations occurring on a timescale of minutes to hours were unlikely to play a direct role in these changes .
however , recent studies indicate that glucocorticoids and related signaling molecules can have much more rapid effects on dendritic spines than were previously suspected .
for example , in hippocampal organotypic cultures , corticotropin - releasing hormone ( crh)a peptide hormone neurotransmitter and upstream regulator of glucocorticoid synthesis 
rapidly increased the retraction and elimination of apical dendritic spines after just 30  min of exposure ( chen et  al . , 2008 ) , providing one potential mechanism for stress - induced deficits in memory recall ( chen et  al . , 2010 ) .
similarly , using transcranial two - photon microscopy to image the dynamic remodeling of postsynaptic dendritic spines in the living , developing cortex ( liston and gan , 2011 ) , we found that glucocorticoids have rapid effects on both spine formation and elimination within hours of exposure .
surprisingly , low - dose dexamethasone ( 0.1  mg / kg ) , a synthetic glucocorticoid that inhibits endogenous corticosteroid synthesis without penetrating the blood / brain barrier ( karssen et  al . , 2005 ) , effectively prevented developmental spine formation and pruning .
it is important to note that studies in neuronal cultures and in the developing cortex are investigating spine remodeling under conditions of heightened plasticity , so additional work will be needed to understand how the results apply to the adult brain . however , these experiments indicate that glucocorticoids play an unexpected , necessary role in facilitating physiological spine maturation in the developing adolescent brain , acting on timescale of minutes to hours to facilitate spine remodeling .
these unexpectedly rapid effects also suggest that circadian glucocorticoid oscillations may contribute to synaptic plasticity during learning and development .
to test this hypothesis , we conducted a series of two - photon imaging studies in mice before and after training on a rotarod motor skill - learning paradigm , and found that circadian glucocorticoid peaks and troughs play critical , complementary roles in facilitating experience - dependent spine remodeling ( fig .  2c 
specifically , circadian glucocorticoid peaks enhanced spine formation rapidly in the hours after learning , acting through a glucocorticoid receptor - dependent , non - transcriptional mechanism . in accord with prior reports ( yang et  al . , 2009 ) , training increased formation rates but only if it occurred during the circadian peak . in mice that were trained during the circadian trough ,
spine formation rates were equivalent to those of untrained mice , and memory retention was reduced one week later .
furthermore , circadian troughs were necessary for stabilizing a subset of learning - related spines and pruning a corresponding set of pre - existing synapses .
memory retention and the long - term survival of learning - related spines required intact circadian troughs in the days after learning , which enhanced learning - related spine pruning through a distinct , mineralocorticoid receptor - dependent , transcriptional mechanism . in this way ,
circadian glucocorticoid oscillations were critical for maintaining homeostasis in synaptic density , by balancing formation and pruning after learning to maintain relatively stable synaptic densities despite repeated bouts of learning - related remodeling .
chronic stress states disrupt this balance . in the same rotarod motor skill - learning study ( liston et  al . , 2013 ) , prolonged glucocorticoid exposure  an important feature of chronic stress states  disrupted circadian troughs , reducing the survival of newly formed spines while simultaneously increasing the elimination of pre - existing synapses .
together , these two effects led to widespread spine loss and reduced spine densities , in striking contrast to the tight coupling between formation and pruning rates that was observed across all other experimental conditions in the study .
related effects were observed on spine maturation across adolescence ( liston and gan , 2011 ) , and in a mouse model of chronic circadian rhythm disruption ( karatsoreos et  al .
notably , disrupted oscillations in chronic stress states have complex effects on synaptic remodeling that are modulated by the developmental trajectories of synapse formation ( fig . 
whereas transient glucocorticoid activity increases the pruning mostly of young , recently formed spines , prolonged glucocorticoid exposure disrupts circadian troughs , eliminating synapses that formed progressively earlier in development ( liston and gan , 2011 , liston et  al . , 2013 ) .
this finding may inform efforts to understand how stress effects interact with synaptic development across the lifespan of an organism .
stress has varying effects on brain function , behavior , and psychiatric risk that depend on when during development the stressor occurs ( lupien et  al . ,
this dependence may relate to the varying trajectories of synaptic development across different brain regions ( lupien et  al . , 2009 ) .
for example , during infancy and early childhood , the hippocampus is developing rapidly and may be particularly vulnerable to early - life stress , whereas protracted development in the prefrontal cortex during the transition from adolescence to early adulthood may increase its vulnerability during this period ( lupien et  al . , 2009 ) .
in accord with this hypothesis , a variety of early - life stressors can induce long - lasting changes in hippocampal corticosteroid receptor expression and hpa reactivity , heightened anxiety , and hippocampus - dependent memory deficits that persist into adulthood ( barbazanges et  al .
, 1996 , valle et  al . , 1999 , lemaire et  al . , 2000 , tsoory et  al . , 2007 , eiland and romeo , 2012 , lui et  al . , 2012 ,
importantly , glucocorticoid activity oscillates not only with the circadian cycle of day and night , but also on a much faster time scale with a period of 12  h ( stavreva et  al . , 2009 , lightman and conway - campbell , 2010 ) .
these ultradian oscillations , which are superimposed on the slower circadian cycle ( fig . 
recent studies have shown that ultradian glucocorticoid rhythms generate cycles of gr - mediated  gene pulsing ,  which regulate gene expression on faster timescales than was previously suspected ( stavreva et  al . , 2009 ) .
facilitated by the rapid , chaperone - mediated recycling of nuclear grs , ultradian gene pulses trigger changes in gr - regulated promoter activity that are tightly coupled to physiological oscillations ( stavreva et  al . , 2009 ) .
ultradian glucocorticoid oscillations penetrate the blood / brain barrier and are preserved within stress - sensitive brain areas ( droste et  al . , 2008 ) , where they probably play an important role in responding to stressors and other environmental stimuli in physiological circumstances .
conversely , in chronic stress models , disruptions of the ultradian oscillation alter gene expression responses in these regions and cause correlated changes in locomotor activity and risk assessment behaviors ( sarabdjitsingh et  al . , 2010a , sarabdjitsingh et  al . , 2010b ) .
whether and how these ultradian oscillations affect synaptic remodeling remains unclear , but they are likely to have important effects , acting potentially through both transcriptional and non - transcriptional mechanisms ( mcewen , 1991 , makara and haller , 2001 , lsel and wehling , 2003 , groeneweg et  al . , 2011 ) . as mentioned above , glucocorticoids can increase spine formation in cortical pyramidal cells by ten - fold in just 20  min , acting through non - genomic signaling pathways ( liston et  al .
similarly , glucocorticoids can rapidly enhance the frequency of miniature excitatory postsynaptic potentials , increasing glutamate release probability by activating a non - genomic , mr - dependent signaling pathway ( karst et  al . , 2005 ) .
similarly rapid effects have been observed in other studies in the prefrontal cortex , hippocampus , amygdala , and hypothalamus ( di et  al . , 2003 ,
, 2011 , popoli et  al . , 2011 , tasker and herman , 2011 ) .
the studies reviewed above indicate that stress and glucocorticoids have potent but complex effects on synaptic remodeling , and understanding the underlying molecular mechanisms is a rapidly emerging area of active investigation .
these studies are challenging due in part to the fact that stress effects on dendritic remodeling , synaptic plasticity , and associated molecular signaling mechanisms vary with the region and developmental age under investigation ( lupien et  al . , 2009 ) .
however , one theme to emerge from this work is that glucocorticoids may engage distinct intracellular signaling mechanisms , depending on the timing of a stressor and the kinetics of the glucocorticoid response .
for example , in response to an acute stressor , glucocorticoids promote memory consolidation and impair working memory ( mcgaugh and roozendaal , 2002 , barsegyan et  al . , 2010 ) through a mechanism involving beta adrenergic- and camp - dependent activation of protein kinase
a in the amygdala and prefrontal cortex ( roozendaal et  al . , 2002 , barsegyan et  al . ,
acutely , glucocorticoids also promote long - term memory retention by enhancing learning - dependent spine formation , acting through a glucocorticoid receptor - dependent non - genomic signaling mechanism that increases lim kinase and cofilin phosphorylation ( liston et  al . , 2013 ) , which stabilizes actin polymers and promotes spine growth ( gu et  al . , 2010
recent reviews underscore the point that acute glucocorticoid exposure modulates multiple additional molecular processes that are relevant in this context : acutely , glucocorticoids potentiate glutamate transmission by increasing presynaptic glutamate release and enhancing ampa and nmda receptor trafficking to postsynaptic membranes ; they activate mapk and camkii signaling pathways that have been linked to transcription - dependent mechanisms for memory consolidation ; and they enhance endocannabinoid signaling , which in turns modulates the release of glutamate and other neurotransmitters ( arnsten , 2009 , campolongo et  al . , 2009 ,
in contrast , chronic glucocorticoid exposure engages a variety of molecular signaling mechanisms that are distinct from those engaged by an acute stressor .
for example , chronic glucocorticoid exposure has effects on glutamate receptor expression that oppose those induced by an acute stressor , reducing the expression of the nmda receptor subunit nr2b and the ampa receptor subunits glur2/3 in the prefrontal cortex ( gourley et  al . , 2009 ) .
chronic stress effects on dendritic atrophy in the hippocampus and prefrontal cortex have also been linked to excessive protein kinase c signaling ( hains et  al . , 2009 ) and reduced expression of neural cell adhesion molecules ( ncam-140 ) ( sandi , 2004 ) .
and chronic glucocorticoid exposure suppresses bdnf transcription in the orbitofrontal cortex ( gourley et  al . , 2009 ) and reduces trkb and erk1/2 signaling in the hippocampus ( gourley et  al . , 2008 ) .
although studies indicate that reduced activity - dependent bdnf secretion probably does not by itself cause spine loss or dendritic atrophy ( hill et  al . , 2005 , magarinos et  al . ,
2011 ) , it is likely that altered bdnf signaling plays a role through interactions with other factors .
stress  especially chronic , uncontrollable stress  is an important risk factor for depression , ptsd , and other anxiety disorders , and stress effects on glucocorticoid oscillations may contribute to this effect .
stress has varying effects on hpa axis activity and glucocorticoid secretion that depend on the timing and nature of the stressor ; on the individual 's subjective perception of the situation ; and likely also on his genetic predisposition to developing stress - related psychiatric conditions ( miller et  al . , 2007 ) . in a recent meta - analysis of 8521 subjects across 107 independent studies ,
the most consistent findings were that chronic stress increases the total daily output of cortisol ( the principal glucocorticoid in humans ) , flattens the diurnal rhythm , and reduces the amplitude of the circadian peak ( miller et  al . , 2007 ) .
. the disruption may be particularly significant during the circadian trough , as unopposed mr activity typically occurs only during the trough when glucocorticoid secretion is low ( reul and de kloet , 1985 , de kloet et  al . , 1998b ) , and a relatively small increase in trough levels could have pronounced effects on glucocorticoid signaling . in conjunction with the studies cited above
, these results suggest that chronic stress may predispose vulnerable individuals to a variety of neuropsychiatric disorders by disrupting the circadian oscillation and especially the circadian trough , reducing the survival of newly formed synapses , and destabilizing synapses formed early in development . converging evidence from both clinical studies and animal models lend support to this hypothesis .
disrupted circadian glucocorticoid cycling is a relatively consistent feature in clinical studies of patients with depression or ptsd ( heim et  al .
, 2000 , holsboer , 2000 , yehuda , 2002 , miller et  al . , 2007 ) .
blunted circadian cortisol oscillations are a feature common to both ptsd and depression ( yehuda et  al .
. however , these two disorders appear to involve opposing changes in total cortisol secretion ( decreased in ptsd , variably increased in depression ) : in ptsd , blunted oscillations are driven primarily by reduced circadian peaks ( yehuda et  al . , 1996 ) , while in depression , they are driven primarily by elevated cortisol secretion during the circadian trough ( yehuda et  al . , 1996 ) , especially in psychotic depression ( sachar et  al . , 1973 , keller et  al . , 2006 ) .
in both disorders , blunted corticol cycling is associated with hippocampal volume loss ( bremner et  al .
1996 ) and partially overlapping alterations in functional connectivity ( davidson et  al . , 2002 ,
, 2004 , greicius et  al . , 2007 , sheline et  al . , 2010 , yin et  al . , 2011 ,
2014 ) , which is consistent with results in animal models indicating that both peaks and troughs are necessary for balancing synaptic formation and pruning .
multiple animal models of depression  including chronic unpredictable stress , chronic social defeat stress , and early life stress  recapitulate neuroendocrine abnormalities found in patients , including blunted glucocorticoid oscillations , elevated glucocorticoid activity , and disrupted circadian troughs ( willner , 1997 , meaney , 2001 , krishnan et  al .
, 2007 , nestler and hyman , 2010 ) . in at least one study , blunted circadian cycling was linked specifically to stress susceptibility : circadian rhythm amplitudes were blunted only in mice that exhibited a vulnerable behavioral phenotype in response to chronic social defeat stress , relative to resilient mice that did not develop depression - like symptoms ( krishnan et  al . , 2007 ) .
in other studies , circadian rhythm disturbances have been causally related to mood symptoms . in a genetic model , mice carrying
a mutation in the clock gene showed a loss of circadian rhythms in locomotor activity and a host of mania - like behavioral symptoms ( roybal et  al . , 2007 ) .
and in an environmentally induced model of circadian rhythm disruption , mice that were housed on a shortened 20-h  light 
dark cycle exhibited learning and structural connectivity deficits comparable to those seen in chronic stress states , including apical dendritic atrophy in mpfc pyramidal cells and pfc - dependent cognitive deficits ( karatsoreos et  al . ,
dark cycle also developed metabolic problems , including obesity , increased leptin levels , and signs of insulin resistance .
shift workers and frequent travelers who suffer from chronic jet lag may experience analogous cognitive and metabolic changes ( sack et  al .
, 2007 , lupien et  al . , 2009 , mcewen , 2012 ) , and in susceptible individuals , travel across time zones may even trigger severe mood episodes requiring psychiatric hospitalization ( jauhar and weller , 1982 ) .
an increasing awareness of the importance of circadian and ultradian glucocorticoid oscillations in learning - related synaptic remodeling may also have implications for efforts to optimize training regimens for promoting motor skill learning , which is known to vary with the time of day in both adolescents and adults ( atkinson and reilly , 1996 , miller et  al .
similarly , disruptions in circadian glucocorticoid oscillations may be an important factor to consider in patients undergoing treatment with corticosteroids , which are frequently used in the management of a variety of common autoimmune disorders .
cognitive complaints and mood symptoms are extremely common but poorly understood side effects of treatment ( brown and suppes , 1998 , otte et  al . , 2007 , cornelisse et  al . , 2011 ) , which could potentially be mitigated by designing treatment regimens to preserve naturally occurring oscillations whenever possible .
converging evidence from animal models and human neuroimaging studies indicates that stress - associated functional connectivity changes are a common feature of depression , ptsd , and other neuropsychiatric conditions and are associated with correlated structural changes in the prefrontal cortex , hippocampus , and other vulnerable brain regions .
these , in turn , may be caused in part by circadian disturbances in glucocorticoid activity .
circadian glucocorticoid peaks and troughs are critical for generating and stabilizing new synapses after learning and pruning a corresponding subset of pre - existing synapses .
chronic stress disrupts this balance , interfering with glucocorticoid signaling during the circadian trough and leading to widespread synapse loss , dendritic remodeling , and behavioral consequences .
these effects interact with synaptic development trajectories that vary across brain regions and may be particularly pronounced during the transition from adolescence to young adulthood , when major neuropsychiatric conditions most commonly emerge .
together these findings provide a model for understanding how stress effects on circadian glucocorticoid oscillations may contribute to connectivity changes and ultimately to the pathophysiology of depression , ptsd , and other disorders .
still , many questions remain , and we conclude by considering a few of them . perhaps most importantly , many of these links remain purely correlative , and it will be critical to test whether and how changes in synaptic remodeling directly affect the function of cortical microcircuits , the integration of information across neuroanatomically distributed networks , and the emergence of behavioral effects and psychiatric symptoms . to this end , the recent development of optogenetic tools for manipulating activity in specific neural circuits will be critical for establishing causal mechanisms ( yizhar et  al .
, 2011 , tye and deisseroth , 2012 , berndt et  al . , 2014 ) .
likewise , recently developed imaging modalities provide a means for testing how structural changes within a given microcircuit affect functional circuit dynamics  another critical , unanswered question .
these methods use genetically encoded calcium indicators ( tian et  al . , 2009 ) to quantify neuronal activity with single - cell precision in the living organism . in combination with implantable optical devices ( flusberg et  al . , 2008 ,
, 2009 , chia and levene , 2009 , andermann et  al . , 2013 ) , these tools will extend the reach of conventional two - photon microscopy to enable in  vivo imaging in the hippocampus , amygdala , medial prefrontal cortex , and other stress - sensitive limbic circuits , which tend to lie deep below the cortical surface .
finally , in  vivo imaging tools may also prove useful for investigating the role of ultradian oscillations , which are superimposed on the circadian glucocorticoid rhythm .
what is clear is that these oscillations trigger pulses of gene expression every 12  h ( stavreva et  al . , 2009 ) , and that glucocorticoids are capable of regulating synapse function and facilitating synapse formation on a comparably rapid timescale ( popoli et  al . , 2011 ,
together , these emerging technologies will enable investigators to ask fundamentally new questions about the links between circadian rhythm disruptions , structural measures of synaptic remodeling , and their functional consequences .
 stress  especially chronic , uncontrollable stress  is an important risk factor for many neuropsychiatric disorders . 
 the underlying mechanisms are complex and multifactorial , but they involve correlated changes in structural and functional measures of neuronal connectivity within cortical microcircuits and across neuroanatomically distributed brain networks . here , we review evidence from animal models and human neuroimaging studies implicating stress - associated changes in functional connectivity in the pathogenesis of ptsd , depression , and other neuropsychiatric conditions . 
 changes in fmri measures of corticocortical connectivity across distributed networks may be caused by specific structural alterations that have been observed in the prefrontal cortex , hippocampus , and other vulnerable brain regions . 
 these effects are mediated in part by glucocorticoids , which are released from the adrenal gland in response to a stressor and also oscillate in synchrony with diurnal rhythms . 
 recent work indicates that circadian glucocorticoid oscillations act to balance synapse formation and pruning after learning and during development , and chronic stress disrupts this balance . 
 we conclude by considering how disrupted glucocorticoid oscillations may contribute to the pathophysiology of depression and ptsd in vulnerable individuals , and how circadian rhythm disturbances may affect non - psychiatric populations , including frequent travelers , shift workers , and patients undergoing treatment for autoimmune disorders . 
Stress effects on structural and functional connectivity
Neuroendocrine mechanisms: glucocorticoid oscillations regulate synaptic remodeling in cortical circuits
Molecular mechanisms of synaptic remodeling by glucocorticoids
Translational implications: circadian glucocorticoid oscillations and the pathogenesis of stress-related neuropsychiatric disorders
Conclusions and future directions