The Role of Sleep in Emotional Brain Function

“Cortisol is also released in response to stressful events (Sapolsky et al 2000), and can independently modulate emotional memory through direct and indirect effects on the hippocampus and amygdala (McIntyre et al 2012, Roozendaal et al 2009, Sapolsky et al 2000).”

“As a consequence of this high tonic background activity, the phasic signals in response to external emotional stimuli result in poor signal-to-noise within the system, and thus reduced specificity (Figure 6b) (Aston-Jones & Cohen 2005, Mallick & Singh 2011, Valentino & Van Bockstaele 2008).”

“…of aversive events, increased anticipatory limbic activity positively predicts clinical features of anxiety disorders, such as worry and rumination (Etkin & Wager 2007, Nitschke et al 2009, Paulus & Stein 2006), many of which express co-occurring impairments in the quantity and quality of sleep…”

“Affective experiences appear to be remembered more robustly than neutral memories due to well characterized set of adrenergic and peripheral autonomic reactions elicited at the time of the experience, orchestrated, in part, by the locus coeruleus (McGaugh 2004).”

“…aims to (1) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep, (2) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep,…”

“…anticipatory limbic activity positively predicts clinical features of anxiety disorders, such as worry and rumination (Etkin & Wager 2007, Nitschke et al 2009, Paulus & Stein 2006), many of which express co-occurring impairments in the quantity and quality of sleep (Papadimitriou & Linkowski 2005).”

“…supporting this theory, and potentially underlying the alterations in salience discrimination, PTSD patients express hyperactivity of the amygdala yet hypoactivity of the PFC; a similar profile to that observed in sleep-deprived healthy controls (Figure 8)(Motomura et al 2013, Yoo et al 2007).”

“…that only through such mapping and hence appreciation of the current state of the body in the frontal lobe, can the brain select appropriate behavioural actions for the organism (actions that include emotion expression) (Craig 2010, Craig 2011, Critchley 2005, Critchley 2009, Harrison et al 2010).”

“…reported in several affective psychopathologies, including major depression, bipolar disorder, generalized anxiety disorder and PTSD (Davidson 2002, Drevets et al 2008, Etkin 2010, Etkin & Wager 2007, Nitschke et al 2009, Paulus & Stein 2006, Rauch et al 2000, Shin et al 2006, Siegle et al 2007).”

“…the mechanisms underlying affective brain processes (Critchley 2005, Delgado et al 2006, Hartley & Phelps 2010, Ochsner et al 2009), translationally bridging animal models of emotion regulation and relevant clinical disorders (Davidson 2002, Delgado et al 2006, Drevets et al 2008, Etkin 2010).”

“…REM sleep represents a neurobiological brain-state particularly amenable to selective emotional memory processing (Hu et al 2006, Pare et al 2002, Walker 2009, Walker & van der Helm 2009), with theta oscillations proposed as a carrier frequency that allows disparate brain regions that initially…”

“…reported in several affective psychopathologies, including major depression, bipolar disorder, generalized anxiety disorder and PTSD (Davidson 2002, Drevets et al 2008, Etkin 2010, Etkin & Wager 2007, Nitschke et al 2009, Paulus & Stein 2006, Rauch et al 2000, Shin et al 2006, Siegle et al 2007).”

“…the mechanisms underlying affective brain processes (Critchley 2005, Delgado et al 2006, Hartley & Phelps 2010, Ochsner et al 2009), translationally bridging animal models of emotion regulation and relevant clinical disorders (Davidson 2002, Delgado et al 2006, Drevets et al 2008, Etkin 2010).”

“P A A uthor M anuscript promote their integration into pre-existing autobiographical memory networks (Cahill 2000, Jones & Wilson 2005).”

“…less well characterized, interaction between sleep and mood states; the latter which we and others considered distinct from emotions (emotions being shortlived events, often in response to external stimuli, while mood states are more sustained events, often internally generated (Mendl et al 2010)).”

“…process of dreaming) critically and perhaps most importantly take place within a brain that is low in aminergic neurochemical concentration (Pace-Schott & Hobson 2002), particularly the suppressed noradrenergic input from the locus coeruleus (associated with stress and anxiety responses…”

“Keywords Sleep; rapid-eye movement (REM); Emotion; Memory; Major Depression; post-traumatic stress disorder (PTSD) Introduction The ability of the human brain to generate, regulate and be guided by emotions represents a fundamental process governing our personal lives, our mental health as well as…”

“…reported in several affective psychopathologies, including major depression, bipolar disorder, generalized anxiety disorder and PTSD (Davidson 2002, Drevets et al 2008, Etkin 2010, Etkin & Wager 2007, Nitschke et al 2009, Paulus & Stein 2006, Rauch et al 2000, Shin et al 2006, Siegle et al 2007).”

“…entrance into REM sleep, (2) increased intensity of REM sleep (indexed in the number of rapid eye movements), and (3) longer duration of REM sleep periods (Armitage 2007, Buysse 2004, Franzen & Buysse 2008, Gottesmann & Gottesman 2007, Harvey et al 2003, Palagini et al 2013, Tsuno et al 2005).”

“…the greater duration and/or intensity of REM sleep often reported in major depression may provide a mechanistic explanation for the abnormally low levels of noradrenaline commonly observed with this condition (Blier & Briley 2011, El Mansari et al 2010, Hamon & Blier 2013, Ordway et al 2003).”

“…that only through such mapping and hence appreciation of the current state of the body in the frontal lobe, can the brain select appropriate behavioural actions for the organism (actions that include emotion expression) (Craig 2010, Craig 2011, Critchley 2005, Critchley 2009, Harrison et al 2010).”

“…neurochemical concentration (Pace-Schott & Hobson 2002), particularly the suppressed noradrenergic input from the locus coeruleus (associated with stress and anxiety responses when highly active) (Itoi & Sugimoto 2010, Ramos & Arnsten 2007, Sullivan et al 1999, Valentino & Van Bockstaele 2008).”

“This is particularly relevant in a clinical context since deficits in the extinction and ability to appropriately utilize surrounding contextual information underlie fear-related disorders such as specific phobia and PTSD (Phelps et al 2004), the latter associated with marked sleep disruption (Germain 2013).”

“Furthermore, total and REM specific sleep deprivation alone, without additional pharmacological intervention, can lead to a rapid antidepressant effect in major depression (reviewed in (Benedetti & Colombo 2011, Wu & Bunney 1990).”

“Moreover, should sleep be a contributing factor, it would represent a novel treatment intervention target (Harvey et al 2011).”

“Given nocturnally, patients with combat PTSD and civilian PTSD both demonstrate a restoration of REM sleep, together with decreases in trauma-dream symptomatology (Calohan et al 2010, Raskind et al 2007, Raskind et al 2003, Taylor et al 2008).”

“Early work demonstrated that such offline emotional memory consolidation could be attributed to late-night sleep, a time period rich in REM sleep (Wagner et al 2001).”

“…consolidation of emotional (and not neutral) memory (Figure 2a&b), but the amount of EEG theta activity (4 – 7 Hz) – a dominant electrical oscillation of REM sleep expressed over the prefrontal cortex – predicts the overnight emotional memory retention benefit (Figure 2c&d) (Nishida et al 2009).”

“P A A uthor M anuscript persist in our autobiographies over time (strengthening of the memory) (Dolcos et al 2005), an equally remarkable but less noted change is a reduction in the affective tone associated with their recall (depotentiation of emotion).”

“…that only through such mapping and hence appreciation of the current state of the body in the frontal lobe, can the brain select appropriate behavioural actions for the organism (actions that include emotion expression) (Craig 2010, Craig 2011, Critchley 2005, Critchley 2009, Harrison et al 2010).”

“It may not be coincidental that these patients additionally continue to display hyperarousal reactions to associated trauma cues (Harvey et al 2003, Pole 2007).”

“The consequence appears to be a pendulum like, bi-directional state of emotion imbalance at both ends of the valence spectrum, fitting early anecdotal reports of affective liability following a lack of sleep (Dahl 1996).”

“Given nocturnally, patients with combat PTSD and civilian PTSD both demonstrate a restoration of REM sleep, together with decreases in trauma-dream symptomatology (Calohan et al 2010, Raskind et al 2007, Raskind et al 2003, Taylor et al 2008).”

“…over the past two decades have helped characterize the mechanisms underlying affective brain processes (Critchley 2005, Delgado et al 2006, Hartley & Phelps 2010, Ochsner et al 2009), translationally bridging animal models of emotion regulation and relevant clinical disorders (Davidson…”

“Post-traumatic stress disorder Building on emerging empirical evidence (Germain et al 2008, Spoormaker & Montgomery 2008), both the above-proposed REM sleep models have relevance to the etiology and pathophysiology of PTSD, as well as understanding recent pharmacological treatment interventions.”

“…entrance into REM sleep, (2) increased intensity of REM sleep (indexed in the number of rapid eye movements), and (3) longer duration of REM sleep periods (Armitage 2007, Buysse 2004, Franzen & Buysse 2008, Gottesmann & Gottesman 2007, Harvey et al 2003, Palagini et al 2013, Tsuno et al 2005).”

“Keywords Sleep; rapid-eye movement (REM); Emotion; Memory; Major Depression; post-traumatic stress disorder (PTSD) Introduction The ability of the human brain to generate, regulate and be guided by emotions represents a fundamental process governing our personal lives, our mental health as well as our societal structu…”

“…in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning, and (3) describe how this hypothesized framework can explain the prevalent relationships…”

“…PTSD not only include hyperarousal and an increased startle response, but also a generalization of the fear response to commonly non-threatening stimuli; the former two indicative of heightened sensitivity, the latter of decreased emotional specificity (Jovanovic et al 2012, Jovanovic et al 2009).”

“Congruently, sleep deprivation also increases sympathetic dominance of the autonomic nervous system, indexed by changes in heart rate variability (Sauvet et al 2010, Zhong et al 2005).”

“This is of particular clinical interest considering that impulsivity is significantly correlated with aggressive behavior and suicidality (Plutchik 1995), both of which are associated with sleep disruption (Bernert & Joiner 2007, Kamphuis et al 2012).”

“Additionally, the success of overnight emotion depotentiation at both a brain (amygdala) and behavioral (intensity ratings) level is predicted by gamma EEG activity – a validated but indirect measure of central adrenergic activity (Berridge & Foote 1991, Cape & Jones 1998, Keane et al 1976).”

“Post-traumatic stress disorder Building on emerging empirical evidence (Germain et al 2008, Spoormaker & Montgomery 2008), both the above-proposed REM sleep models have relevance to the etiology and pathophysiology of PTSD, as well as understanding recent pharmacological treatment interventions.”

“Of further relevance, both objective sleep disturbances occurring in the immediate aftermath of trauma exposure, as well as heightened sympathetic vagal tone during REM sleep, are associated with an increased risk of PTSD (Koren et al 2002, Mellman et al 2002).”

“Of further relevance, both objective sleep disturbances occurring in the immediate aftermath of trauma exposure, as well as heightened sympathetic vagal tone during REM sleep, are associated with an increased risk of PTSD (Koren et al 2002, Mellman et al 2002).”

“Modified from (van der Helm et al 2011).”

“Congruently, one night of experimentally controlled sleep loss increases subjective reports of stress, anxiety and anger in response to low-stress situations (Minkel et al 2012), and increases impulsivity towards negative stimuli (Anderson & Platten 2011).”

“…increased anticipatory limbic activity positively predicts clinical features of anxiety disorders, such as worry and rumination (Etkin & Wager 2007, Nitschke et al 2009, Paulus & Stein 2006), many of which express co-occurring impairments in the quantity and quality of sleep (Papadimitriou &…”

“…associated with elevated reactivity to food stimuli in salience and hedonic regions of the striatum and amygdala, together with blunted activity in appetitive choice and decision making regions of the frontal cortex (Benedict et al 2012, Greer et al 2013, Killgore et al 2013, St-Onge et al 2012).”

“…the mechanisms underlying affective brain processes (Critchley 2005, Delgado et al 2006, Hartley & Phelps 2010, Ochsner et al 2009), translationally bridging animal models of emotion regulation and relevant clinical disorders (Davidson 2002, Delgado et al 2006, Drevets et al 2008, Etkin 2010).”

“It is just such a cycle of REM sleep dreaming (nightmares) that represents a diagnostic key feature of PTSD (Lavie 2001).”

“One night of sleep deprivation elevates anticipatory activity within the reward-sensitive region of the striatum to monetary decisions that can lead to either future reward payoffs or losses – especially when those gambles are risky (Venkatraman et al 2007).”

“…entrance into REM sleep, (2) increased intensity of REM sleep (indexed in the number of rapid eye movements), and (3) longer duration of REM sleep periods (Armitage 2007, Buysse 2004, Franzen & Buysse 2008, Gottesmann & Gottesman 2007, Harvey et al 2003, Palagini et al 2013, Tsuno et al 2005).”

“Second, in the context of reward sensitivity, sleep disturbance is a recognized hallmark of addiction (Arnedt et al 2007, Brower & Perron 2010, Dimsdale et al 2007, Pace-Schott et al 2005), leading to the recent proposal that sleep loss represents a common and reliable predictor of relapse in…”

“Moreover, these reports offer tentative neural explanations for the pervasive co-occurrence of sleep abnormalities in psychiatric disorders (Armitage 2007, Buysse 2004, Franzen & Buysse 2008, Gottesmann & Gottesman 2007, Harvey et al 2003, Tsuno et al 2005).”

“Given nocturnally, patients with combat PTSD and civilian PTSD both demonstrate a restoration of REM sleep, together with decreases in trauma-dream symptomatology (Calohan et al 2010, Raskind et al 2007, Raskind et al 2003, Taylor et al 2008).”

“P A A uthor M anuscript subjective intensity ratings of threat-relevant (angry) and reward-relevant (happy) static facial expressions (van der Helm et al 2010).”

“Similarly, PTSD patients produce a fear response of equal magnitude to both threat and non-threat related stimuli, preventing emotion discrimination, while healthy controls show specificity only to threat cues (Grillon & Morgan 1999).”

“…that only through such mapping and hence appreciation of the current state of the body in the frontal lobe, can the brain select appropriate behavioural actions for the organism (actions that include emotion expression) (Craig 2010, Craig 2011, Critchley 2005, Critchley 2009, Harrison et al 2010).”

“Emerging evidence suggests exactly this profile: patients with major depression express non-specific amygdala reactivity that does not discriminate between negative, neutral and positive images (Ritchey et al 2011).”

“This results in a similar tonic firing profile in the amygdala (Figure 6b) (again through the beta receptor type) (Mallick & Singh 2011, van Marle et al 2009, van Marle et al 2011), resulting in low emotional signal-to-noise reactivity, decreasing specificity (the ability to discriminate stimuli…”

“…PTSD not only include hyperarousal and an increased startle response, but also a generalization of the fear response to commonly non-threatening stimuli; the former two indicative of heightened sensitivity, the latter of decreased emotional specificity (Jovanovic et al 2012, Jovanovic et al 2009).”

“…associated with elevated reactivity to food stimuli in salience and hedonic regions of the striatum and amygdala, together with blunted activity in appetitive choice and decision making regions of the frontal cortex (Benedict et al 2012, Greer et al 2013, Killgore et al 2013, St-Onge et al 2012).”

“Moreover, this preferential emotional memory retention persists years later (Wagner et al 2006).”

“…the brain areas recognized to support fear acquisition and extinction (mPFC, amygdala, hippocampus) are all reactivated during REM sleep (Dang-Vu et al 2010, Miyauchi et al 2009, Nofzinger 2005, Phelps et al 2004), and through such REM sleep brain network restoration, may aide the…”

“Evidence for all three of these predictions exists (Nishida et al 2009, Pare et al 2002).”

“…associated with elevated reactivity to food stimuli in salience and hedonic regions of the striatum and amygdala, together with blunted activity in appetitive choice and decision making regions of the frontal cortex (Benedict et al 2012, Greer et al 2013, Killgore et al 2013, St-Onge et al 2012).”

“Congruently, sleep deprivation also increases sympathetic dominance of the autonomic nervous system, indexed by changes in heart rate variability (Sauvet et al 2010, Zhong et al 2005).”

“…if participants are not allowed to sleep the first night after being exposed to aversive emotional stimuli, there is a failure of subsequent amygdala depotentiation to the same emotional stimulus during a memory test, even following two nights of recovery sleep (Sterpenich et al 2007).”

“Congruently, the presence of insomnia in war veterans during the 4 months after deployment is a significant predictor of PTSD symptom development (Wright et al 2011).”

“This is of particular clinical interest considering that impulsivity is significantly correlated with aggressive behavior and suicidality (Plutchik 1995), both of which are associated with sleep disruption (Bernert & Joiner 2007, Kamphuis et al 2012).”

“…anticipatory limbic activity positively predicts clinical features of anxiety disorders, such as worry and rumination (Etkin & Wager 2007, Nitschke et al 2009, Paulus & Stein 2006), many of which express co-occurring impairments in the quantity and quality of sleep (Papadimitriou & Linkowski 2005).”

“…neurochemical concentration (Pace-Schott & Hobson 2002), particularly the suppressed noradrenergic input from the locus coeruleus (associated with stress and anxiety responses when highly active) (Itoi & Sugimoto 2010, Ramos & Arnsten 2007, Sullivan et al 1999, Valentino & Van Bockstaele 2008).”

“…that only through such mapping and hence appreciation of the current state of the body in the frontal lobe, can the brain select appropriate behavioural actions for the organism (actions that include emotion expression) (Craig 2010, Craig 2011, Critchley 2005, Critchley 2009, Harrison et al 2010).”

“Similar enhanced mesolimbic reactivity following sleep deprivation can occur using monetary reward incentive paradigms (Libedinsky et al 2011, McKenna et al 2007, Venkatraman et al 2007).”

“Cortisol is also released in response to stressful events (Sapolsky et al 2000), and can independently modulate emotional memory through direct and indirect effects on the hippocampus and amygdala (McIntyre et al 2012, Roozendaal et al 2009, Sapolsky et al 2000).”

“Additionally, inter-individual differences in the change in connectivity between the amygdala and mPFC caused by sleep deprivation accurately predicts the concurrent increase in subjective anxiety (Motomura et al 2013).”

“Crucially, every one of these clinical conditions expresses highly comorbid sleep disruption (Harvey 2011, Peterson & Benca 2006), and in some of these disorders, sleep abnormalities form part of their diagnostic criteria.”

“…the mechanisms underlying affective brain processes (Critchley 2005, Delgado et al 2006, Hartley & Phelps 2010, Ochsner et al 2009), translationally bridging animal models of emotion regulation and relevant clinical disorders (Davidson 2002, Delgado et al 2006, Drevets et al 2008, Etkin 2010).”

“…disturbance is a recognized hallmark of addiction (Arnedt et al 2007, Brower & Perron 2010, Dimsdale et al 2007, Pace-Schott et al 2005), leading to the recent proposal that sleep loss represents a common and reliable predictor of relapse in numerous addiction disorders (Brower & Perron 2010).”

“These included marked fragmentation of REM sleep (Breslau et al 2004, Habukawa et al 2007, Mellman et al 2002) (indicative of arousal-related awakenings from REM sleep linked to adrenergic surges), and increases sympathetic tone of the autonomic nervous system (Harvey et al 2003, Mellman & Hipolito…”

“Furthermore, the degree of the nocturnal noradrenaline alterations are negatively correlated with measures of sleep quality in both control and PTSD groups, such that greater noradrenaline concentrations across the night are associated with worse sleep quality (Mellman et al 1995).”

“Recent evidence demonstrates that three-year-olds who do not obtain an afternoon nap show dysregulation of both positive and negative emotional expression in response to emotional stimuli, relative to those who have obtained a nap (Berger et al 2012).”

“…neurochemical concentration (Pace-Schott & Hobson 2002), particularly the suppressed noradrenergic input from the locus coeruleus (associated with stress and anxiety responses when highly active) (Itoi & Sugimoto 2010, Ramos & Arnsten 2007, Sullivan et al 1999, Valentino & Van Bockstaele 2008).”

“…responses, recent evidence demonstrates that sleep, relative to time spent awake, preferentially modifies the appropriate expression of fear, depending on whether the conditioned stimulus (the tone) is presented in an unsafe or a safe surrounding context (Menz et al 2013, Pace-Schott et al 2009).”

“…optimally preparing the organism for next-day social and emotional functioning, and (3) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on post-traumatic stress disorder and major depression.”

“Thus, sleep (and not wake) can separate emotionally relevant from irrelevant components of a single memory experience for selective consolidation (Payne et al 2012).”

“Additionally, the success of overnight emotion depotentiation at both a brain (amygdala) and behavioral (intensity ratings) level is predicted by gamma EEG activity – a validated but indirect measure of central adrenergic activity (Berridge & Foote 1991, Cape & Jones 1998, Keane et al 1976).”

“Cortisol is also released in response to stressful events (Sapolsky et al 2000), and can independently modulate emotional memory through direct and indirect effects on the hippocampus and amygdala (McIntyre et al 2012, Roozendaal et al 2009, Sapolsky et al 2000).”

“…first on consolidation a night of sleep consolidates and strengthens conditioned fear responses (neural, physiological and behavioral) compared to the absence of intervening sleep, and as a consequence, results in superior discrimination of fear-related from non-fearrelated cues (Menz et al 2013).”

“PTSD has been associated not only with decreases in the total time spent in REM sleep (Germain 2013, Lavie et al 1979, Mellman et al 1997), but also qualitative REM sleep abnormalities.”

“…skin conductance), and with it, the beneficial re-engagement of ventromedial PFC (vmPFC) involvement during post-sleep fear extinction recall (Spoormaker et al 2012) The latter finding is relevant considering the vmPFC is a region know to be necessary for successful development of lasting…”

“…the greater duration and/or intensity of REM sleep often reported in major depression may provide a mechanistic explanation for the abnormally low levels of noradrenaline commonly observed with this condition (Blier & Briley 2011, El Mansari et al 2010, Hamon & Blier 2013, Ordway et al 2003).”

“Therefore, REM sleep may serve an noradrenergic “housekeeping” function, one that reduces and thus restores concentrations of noradrenaline to baseline each day (in humans), allowing for optimal waking functioning (Mallick & Singh 2011, Siegel & Rogawski 1988).”

“In contrast, sleep deprivation is associated with increased fear responding to non-threating cues (Menz et al 2013, Pace-Schott et al 2009, Spoormaker et al 2012, Spoormaker et al 2010), indicative of a failure to appropriately discriminate between threatening and non-threatening information.”

“Moreover, habitual subjective sleep quality outside of the laboratory is also significantly related to amygdala reactivity, as well as features of negative affect and stress (Prather et al 2013).”

“PTSD has been associated not only with decreases in the total time spent in REM sleep (Germain 2013, Lavie et al 1979, Mellman et al 1997), but also qualitative REM sleep abnormalities.”

“…is a substantial reduction in levels of noradrenaline (norepinephrine) during REM sleep, falling to concentrations below that of either NREM sleep or wake (Kametani & Kawamura 1990, Marrosu et al 1995, Ouyang et al 2004, Park 2002, Shouse et al 2000); the lowest of any time during the 24hr period.”

“Similarly, decreases in the vocal expression of positive emotion by deprived participants is observed after a single night of sleep loss, suggesting that multiple routes of emotional expression (e.g. facial muscles, vocalizations) are compromised by insufficient sleep (McGlinchey et al 2011).”

“Moreover, experimentally increasing and decreasing cortisol concentrations prior to sleep can bi-directionally alter the magnitude of emotional memory consolidation during sleep (van Marle et al 2013, Wagner et al 2005).”

“Sleep loss additionally decreases the outward expression of emotion by sleep-deprived individual themselves, as judged by expert raters (Minkel et al 2011).”

“Furthermore, total and REM specific sleep deprivation alone, without additional pharmacological intervention, can lead to a rapid antidepressant effect in major depression (reviewed in (Benedetti & Colombo 2011, Wu & Bunney 1990).”

“…et al 2004, Habukawa et al 2007, Mellman et al 2002) (indicative of arousal-related awakenings from REM sleep linked to adrenergic surges), and increases sympathetic tone of the autonomic nervous system (Harvey et al 2003, Mellman & Hipolito 2006) (reflective of heightening adrenergic activity).”

“…intervention promise: patients who slept immediately after exposure treatment—a form of fear extinction learning—showed greater subjective reductions in anxiety and negative cognition one week after treatment, relative to those who remain awake for some time after treatment (Kleim et al 2013).”

“…is a substantial reduction in levels of noradrenaline (norepinephrine) during REM sleep, falling to concentrations below that of either NREM sleep or wake (Kametani & Kawamura 1990, Marrosu et al 1995, Ouyang et al 2004, Park 2002, Shouse et al 2000); the lowest of any time during the 24hr period.”

“Second, in the context of reward sensitivity, sleep disturbance is a recognized hallmark of addiction (Arnedt et al 2007, Brower & Perron 2010, Dimsdale et al 2007, Pace-Schott et al 2005), leading to the recent proposal that sleep loss represents a common and reliable predictor of relapse in…”

“…is a substantial reduction in levels of noradrenaline (norepinephrine) during REM sleep, falling to concentrations below that of either NREM sleep or wake (Kametani & Kawamura 1990, Marrosu et al 1995, Ouyang et al 2004, Park 2002, Shouse et al 2000); the lowest of any time during the 24hr period.”

“P A A uthor M anuscript promote their integration into pre-existing autobiographical memory networks (Cahill 2000, Jones & Wilson 2005).”

“These included marked fragmentation of REM sleep (Breslau et al 2004, Habukawa et al 2007, Mellman et al 2002) (indicative of arousal-related awakenings from REM sleep linked to adrenergic surges), and increases sympathetic tone of the autonomic nervous system (Harvey et al 2003, Mellman & Hipolito…”

“significantly correlated with aggressive behavior and suicidality (Plutchik 1995), both of which are associated with sleep disruption (Bernert & Joiner 2007, Kamphuis et al 2012).”

“Moreover, an increase in REM sleep quantity/quality at night, either through pharmacological intervention (Stern & Morgane 1974, Taylor et al 2008) or through psychopathology states such as major depression (Blier & Briley 2011, El Mansari et al 2010, Hamon & Blier 2013, Ordway et al 2003), would…”

“…prescribed for treating major depression—both of which increase noradrenaline concentrations (Hamon & Blier 2013, Holshoe 2009, Tribl et al 2013, Trivedi & Daly 2008)—restore REM sleep features in major depression, prolonging the time it takes to enter REM sleep and decreasing the total Annu…”

“…in a predominantly phasic manner i.e. selectively, to salient stimuli within the environment (i.e. salience “signal”), while maintaining a low level of baseline (tonic) ongoing activity (i.e. background “noise”) (Aston-Jones & Cohen 2005, Mallick & Singh 2011, Valentino & Van Bockstaele 2008).”

“…of reward sensitivity, sleep disturbance is a recognized hallmark of addiction (Arnedt et al 2007, Brower & Perron 2010, Dimsdale et al 2007, Pace-Schott et al 2005), leading to the recent proposal that sleep loss represents a common and reliable predictor of relapse in numerous addiction…”

“Similar enhanced mesolimbic reactivity following sleep deprivation can occur using monetary reward incentive paradigms (Libedinsky et al 2011, McKenna et al 2007, Venkatraman et al 2007).”

“…optimally preparing the organism for next-day social and emotional functioning, and (3) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on post-traumatic stress disorder and major depression.”

“…reuptake inhibitors prescribed for treating major depression—both of which increase noradrenaline concentrations (Hamon & Blier 2013, Holshoe 2009, Tribl et al 2013, Trivedi & Daly 2008)—restore REM sleep features in major depression, prolonging the time it takes to enter REM sleep and…”

“…in the noradrenergic system in PTSD. Based on recent neuroimaging data, patients with PTSD express exaggerated locus coeruleus activity during REM sleep compared to controls, suggesting a persistence (rather than normal quiescence) of the noradrenergic system in REM sleep (Germain et al 2013).”

“Additionally, a prospective study has demonstrated that sleep problems assessed during childhood significantly predict early onset of drug and alcohol use years later in adolescence, even when controlling for effects of anxiety and attention deficits (Volkow et al 2009).”

“…the greater duration and/or intensity of REM sleep often reported in major depression may provide a mechanistic explanation for the abnormally low levels of noradrenaline commonly observed with this condition (Blier & Briley 2011, El Mansari et al 2010, Hamon & Blier 2013, Ordway et al 2003).”

“In addition to diminishing outward emotive expression, sleep deprivation also slows the generation of facial reactions in response to visual presentation of faces (Schwarz et al 2013).”

“…reuptake inhibitors prescribed for treating major depression—both of which increase noradrenaline concentrations (Hamon & Blier 2013, Holshoe 2009, Tribl et al 2013, Trivedi & Daly 2008)—restore REM sleep features in major depression, prolonging the time it takes to enter REM sleep…”

“Given nocturnally, patients with combat PTSD and civilian PTSD both demonstrate a restoration of REM sleep, together with decreases in trauma-dream symptomatology (Calohan et al 2010, Raskind et al 2007, Raskind et al 2003, Taylor et al 2008).”

“Moreover, experimentally increasing and decreasing cortisol concentrations prior to sleep can bi-directionally alter the magnitude of emotional memory consolidation during sleep (van Marle et al 2013, Wagner et al 2005).”

“…is a substantial reduction in levels of noradrenaline (norepinephrine) during REM sleep, falling to concentrations below that of either NREM sleep or wake (Kametani & Kawamura 1990, Marrosu et al 1995, Ouyang et al 2004, Park 2002, Shouse et al 2000); the lowest of any time during the 24hr period.”

“Additionally, the success of overnight emotion depotentiation at both a brain (amygdala) and behavioral (intensity ratings) level is predicted by gamma EEG activity – a validated but indirect measure of central adrenergic activity (Berridge & Foote 1991, Cape & Jones 1998, Keane et al 1976).”

“Given that the brain structures and neurochemicals involved in the regulation of emotion also govern sleep [9], and nearly all affective disorders co-occur with sleep abnormalities [1,2], an intimate relationship between these two domains of functioning is intuitive.”

“Moreover, depression and post-traumatic stress disorder (PTSD)–associated with REM sleep disturbance [95]–are risk factors for developing AD [99,100].”