Sleep and Trauma for MCQs.pdf

Sleep and Trauma Maya Schenker 1 September 2023 email: [email protected] Overview 1. Background • Post-traumatic stress disorder • Sleep • Bi-directional relationship between sleep and PTSD 2. Mechanistic role of sleep in PTSD (PhD project) • Fear conditioning and extinction learning...

Sleep and Trauma Maya Schenker 1 September 2023 email: [email protected] Overview 1. Background • Post-traumatic stress disorder • Sleep • Bi-directional relationship between sleep and PTSD 2. Mechanistic role of sleep in PTSD (PhD project) • Fear conditioning and extinction learning • Objective sleep • Subjective sleep 3. Everyday role of sleep in PTSD • Association of sleep with day-to-day variability of PTSD symptoms Background: Posttraumatic Stress Disorder (DMS-V) Criterion A: Trauma (death, threatened death, actual or threatened serious injury, actual or threatened sexual violence) Criterion B: Intrusive Symptoms (e.g., nightmares, flashbacks) Criterion C: Avoidance of trauma-related thoughts, feelings, or external reminders Criterion D: Negative alterations in cognition and mood (e.g., inability to recall key features of trauma, negative thoughts or assumptions about oneself or the world, decreased interest in activities) Criterion E: alterations in arousal and reactivity (e.g., aggression, hypervigilance, difficulties sleeping) Criterion F: symptoms experienced for > 1 month and (Criterion G) they cause clinically significant distress or impairment in important areas of functioning Criterion H: symptoms not attributable to physiological effects of a substance or other medical condition. Sleep and PTSD – post-trauma (Pace-Schott et al., 2015) Possible pathways whereby sleep disruption accompanying acute response to trauma can lead to PTSD.  In vulnerable individuals, acute post-traumatic insomnia can become chronic and disrupt processes of sleep-dependant emotional memory consolidation, thereby contributing to the aetiology of PTSD.  Chronic sleep disruption can subsequently perpetuate PTSD symptoms by continued interference with normal processing of emotional memories as well as impaired consolidation of therapeutic extinction memories if exposure therapy has been initiated. Insomnia and PTSD feed into each other in a vicious cycle. Sleep in PTSD (Zhang et al., 2019) Those with PTSD had significantly: • • • • Less total sleep time (TST) More wake after sleep onset (WASO) Less sleep efficiency (time asleep relative to time in bed) Less SWS (ie the deep restorative sleep) than healthy controls. Otherwise, no other significant differences. Sleep and PTSD are bidirectionally linked Evidence that sleep disturbances are a core feature of PTSD and a central mechanism in the development, maintenance and recovery of PTSD. Insomnia plays a role in the development, maintenance, and recovery of the disorder and the same for PTSD. Chicken and egg: PSTD can lead to insomnia and insomnia/sleep disturbance can heighten the traumatic effect of an event i.e. can contribute to the development of PTSD. Difficult to study as can’t expose someone to PTSD. One available sample is in the military population. Koffel et al 2013: looked at military population and whether if had pre-deployment sleep disruption predicted PTSD symptoms: yes it does – up to 2 years after return from war zone Fan et al., 2017: measured sleep disturbances one year after an earthquake. If students had increased sleep disturbances during or shortly post event this increased likelihood of developing PTSD up to 2 years later Development of PTSD Maintenance of PTSD Recovery from PTSD Gold standard for PTSD treatment is prolonged exposure (PE) or CBT – even if patients did PE or CBT – and PSTD symptoms reduced, sleep disturbances continued BUT if sleep disturbances are targeted first (with eg CBT-I) can reduce PTSD symptom severity as well Evidence that treating insomnia (eg with CBT-I) reduces PTSD symptom severity but not vice versa (ie treating PTSD does not result in less sleep disturbances. Interim Summary I Sleep disturbances are a core feature of PTSD and a central mechanism in the development, maintenance and recovery of PTSD and they influence each other bi-directionally. Sleep Gold standard is to do a PSG (polysomnography) to measure brainwaves during sleep and then stage sleep into the 3 nonREM progressively deeper levels of sleep and then to REM sleep. NREM sleep (N3) – SWS large slow waves reflect broadly synchronized activity of cortical neurons, considered essential for broad homeostatic recovery, including synaptic homeostatic functions relevant to memory and cognition. REM sleep has been associated with emotional processing (i.e., processing of emotional information e.g., emotional memories). Emotional fear learning and memory (i.e., extinction learning and safety learning). When usually have vivid sometimes bizarre dreams and that can wake up from: usually disconnect between brain and body (skeletal paralysis). Usually, 1st half of night is SWS (NREM N3) and 2nd half of night is more REM sleep. Rasche & Born 2013 About Sleep’s Role in Memory https://doi.org/10.1152/physrev.00032.2012 Role of REM in Emotional Memory Processing (Goldstein & Walker, 2014) 2 models/hypotheses: 1. ‘Sleep to remember, sleep to forget’ hypothesis Over time the facts around the memory consolidate but the affective tone associated with the memory dissipates – REM sleep/time heals every wound. 2. ’REM sleep emotion recalibration’ model  Normal levels of REM sleep can restore optimal adaptive emotional reactivity.  Discriminate between salient stimuli (threatening/ rewarding) and non-salient stimuli. Zhang et al., 2019 (above) meta-analysis found overall no difference in REM sleep between the PTSD and healthy controls which is surprising given how important REM sleep is. But might depend upon • • the age of the patients with PTSD; and the type of trauma. Significantly less REM % in younger PTSD patients i.e., those <30 years: Forest plot for meta-analysis of the difference in REM percentage between patients with PTSD and controls in studies in which PTSD patients had a mean age < 30 years Significantly less REM% in non-combat PTSDs vs. healthy controls Forest plot for meta-analysis of the difference in REM sleep percentage between patients with PTSD and controls in studies in which the trauma type is non-combat exposure. Non-combat PTSDs had significantly less REM% compared to healthy controls. But overall, there was not a significant relationship between REM sleep and PTSD. Mechanisms underlying PTSD Fear conditioning is an adaptive form of associative learning. Pavlovian fear conditioning and extinction learning (Pavlov, 1927) is an experimental paradigm that allows us to study how emotional memories are learned and remembered. A neutral stimulus (NS) e.g., a pink light, is paired with a threat or aversive to stimulus (unconditioned stimulus; US) – e.g., electric shock to hand; air puff to the throat; scream into earphones. After repeated pairing a fear conditioning process occurs whereby the NS gains predictive threat capacity and becomes the conditioned stimulus (CS+) and can elicit the response by itself. A second neutral stimulus is presented but is never paired with the unconditioned stimulus - this is the CS- or safety stimulus. Extinction of the conditioned fear occurs when the CS+ is repeatedly presented without the aversive stimulus leading to a reduction in the fear response towards the initial NS. Following extinction learning a new memory trace is formed which likely inhibits the previously acquired conditioned association. The strength of the inhibitory extinction memory is tested 24-48 hours later during extinction recall. Psychophysiological conditioned response is usually measured using fear potentiated startle (FPS), or skin conductance response (SCR). Fear learning Have a conditioned response (CS+). Safety learning Is a control condition. Laing et al., 2021 (CS-) Extinction Learning and Recall Presents both stimulus (CS+ and CS-) but after time realise that CS+ is not predicting the shock. Is not updating the initial memory but is the formation of a new, inhibitory memory trace (Milad et al., 2012). Is like a competitive memory trace. This is important because usually memory recall is tested 24-48 hours afterwards and if it was the same memory being reconsolidated then would not expect the fear to return because the original memory is gone (updated) but as fear can return over time, we measure the strength between the 2 memory traces during recall (show the two circle colours and measure whether get a fear response). Key mechanisms underlying PTSD Central mechanisms underlying the development and maintenance of PTSD are impairments in: 1. Extinction learning (Zuj et al., 2016) - struggle to learn the second inhibitory trace: REM sleep should help. 2. Extinction recall (e.g., Garfinkel et al., 2014) – have a higher fear response to stimuli that is not dangerous at home but might be in a war zone (e.g., a loud bang) 3. Differentiating between threatening (CS+) and safe (CS-) cues (van Rooij & Jovanovic, 2019): emotion recalibration What role does REM sleep play in the mechanisms underlying PTSD? Sleep and fear conditioning paradigms High heterogeneity among the findings • Samples: healthy controls vs clinical samples • Settings: measure overnight; daytime nap; sleep vs wakefulness; partial sleep deprivation (1st SWS and/or 2nd half of night REM) • Operationalisation of outcome variables: whole literature around how to define and measure “extinction recall” - is it the level of reactivity experienced during exposure to conditioned stimuli during recall, or is it a difference of fear response during acquisition compared to response upon extinction; the recall phase involves many trials so after a certain number of trials, is it relearning rather than recall? • Directionality of effect: some found REM sleep is better for extinction recall and others that REM sleep is better for fear recall (contradictory) • So apart from REM sleep playing a role in PTSD, is little consensus as to what that role is. Association between sleep and acquisition, extinction and recall of conditioned fear: a meta-analysis Schenker, M. T., Ney, L. J., Miller, L. N., Felmingham, K. L., Nicholas, C. L., & Jordan, A. S. (2021). Sleep and fear conditioning, extinction learning and extinction recall: A systematic review and metaanalysis of polysomnographic findings. Sleep Medicine Reviews, 59, 101501. Q1: Is sleep (particularly REM sleep) associated with the acquisition or extinction of conditioned fear? Q2: Is acquisition or extinction of conditioned fear associated with (particularly REM) sleep? Isn’t this the same as Q1??? Q3: Is sleep (particularly REM sleep) associated with the recall of fear extinction memories? Most important association because of its longer-term implications in telling us something about which of the two memory traces are stronger Summary of included studies: 13 studies identified, 11 included in meta-analysis:      276 participants (f: 110), 25.8 (+/-5.7) years old 2 studies in clinical samples (1 PTSD, 1 chronic insomnia) 2 home-based, 3 afternoon nap 2 with sleep intervention (sleep deprived) 2 FPS, rest Skin Conduction Response Data synthesis and analysis:  Meta-analysis based on correlation between sleep stage % and physiological reactivity to the CS+/CS- to measure the level of fear. Found no effect of REM sleep upon fear conditioning, extinction learning, and extinction recall. Results were surprising as literature that REM sleep was important for fear extinction recall. Sex as a moderator Sex might influence (moderate) the relationship between REM sleep and extinction recall Sex plays critical role in PTSD:  Woman have twice the risk of developing PTSD compared to men, even after controlling for type of trauma exposure (Blanco et al., 2018; Felmingham et al., 2010; Kessler et al., 2017)  Higher prevalence of certain trauma between sexes (Blanco et al., 2018) o Women: interpersonal trauma (e.g., physical abuse, witness, or victim to domestic violence) o Men: situational trauma (e.g., combat, life-threatening accident, natural disaster, witness someone being killed, etc) Why might women be more vulnerable to PTSD? One reason might be sex hormones. Sex hormones play a critical role in fear conditioning and extinction learning (Li & Graham, 2017): Studies have found that if extinction learning in women when oestrogen levels are high, this facilitated the loss of fear conditioning response i.e., had greater extinction recall during recall learning but if learning extinction when oestrogen was low, this impaired the loss of conditioned fear during extinction learning resulting in impaired extinction recall Meta-regression: Sex as a moderator A moderation analysis – does the strength/direction of effect changes with the inclusion of the moderator? Differences in proportion of male to female participants. Sex as a percentage of female participants (not the data of the participants themselves). With increasing % of female participants, the correlation between REM sleep % and fear extinction recall went from negative (in male only sample) to positive (in higher % female samples). For males: more REM sleep means greater extinction recall (lower physiological reactivity during presentation of the CS+ or CS- during extinction recall) For females: more REM sleep is associated with greater conditioned response indicating impaired extinction recall. Interim Summary II  To date, overall is no evidence for REM sleep to be associated with fear conditioning, extinction learning or extinction recall.  Opposite effect of REM sleep on fear extinction recall in men and women.  Limited research in clinical populations.  More research needed to further investigate the role of sex in the sleep-fear conditioning relationship. Objective vs. subjective sleep in PTSD Limitations in measuring objective sleep with PSG:  Paradoxical insomnia in PTSD o Discrepancy between objective and subjective sleep disturbance (Klein et al., 2003; Werner 2016) o The meta-analysis did not find a difference in REM sleep % between PTSD and healthy controls which is probably due to REM sleep disturbances subside with increasing trauma chronicity: the longer ago the trauma was, the more REM sleep recovers (Zhang et al., 2019)  No measure of sleep perception or sleep quality  However, subjective sleep has high clinical implications on daytime functioning.  Is some evidence suggesting an association between subjective sleep and fear conditioning and extinction learning (Zuj et al., 2018) but evidence is limited and very few looking at REM sleep and extinction recall. Subjective sleep in fear conditioning paradigm Schenker et al., 2022 under review Aim: whether subjectively measured sleep disturbances (during baseline) were associated with fear conditioning and extinction learning or if sleep disturbances recorded during the time between fear extinction learning and recall was associated with extinction recall. Included sex as a moderator and included symptom severity as a dimensional factor to see if the associations were stronger with increasing PTSD symptom severity. Hypotheses: H1: Baseline sleep disturbances are associated with heightened fear conditioning and extinction learning. H2: Between-session sleep disturbances are associated with worse extinction recall. H3: These associations are stronger with increasing PTSD symptom severity and in women. Methods: 248 participants, 17-69 years (M = 25.94, SD = 10.02); 57.66% female  PTSD: n=47 (f: 57.45%)  trauma exposed, no PTSD: n=104 (f: 57.69%)  non-trauma exposed: n=97 (f: 57.73%) Subjective sleep - results No association between baseline/consolidation period sleep disturbances (PSQI sleep disturbance component) and acquisition and extinction of fear. No association between sleep onset latency, wake after sleep onset or sleep efficiency and recall of fear extinction. But what about sex?: found a significant moderating effect of sex on extinction recall – found a significant three-way interaction between SOL, PCL scores (PTSD symptom severity and sex which means that in females, shorter SOL and higher PCL scores, were associated with lower SCR towards CS+ but no evidence in males – so women with higher PTSD severity and shorter SOL had a lower fear response at recall towards the CS+. Similar effect was found for sleep efficiency Interim Summary III • lack of finding might be due to small number of males with PTSD (so underpowered) Outlook: translate findings to real world Previous studies looked objective and subjective sleep- related mechanisms underlying the development, maintenance, and treatment of PTSD.  Can we translate these findings to the real world (expression of mechanisms)?  Does sleep predict next-day post-traumatic stress symptom (PTSS) severity and vice-versa? (Schenker et al., 2022, in progress)  Is there any differences between males/females and between objective/ subjective sleep? Current project: Association between PTSS variability and sleep Methods:  Ecological Momentary Assessment (EMA) o Monitoring PTSS o Measuring subjective sleep (diary)  Actigraphy o Measuring objective sleep o Disadvantages (no sleep architecture) and inactivity in night can be scored as asleep and someone who is active but asleep might be recorded as aawke  Trauma-exposed individuals with a range of PTSS  Over 28 days Schenker et al., 2022, in progress Take home messages: