Towards a Post-exposition Pharmacological Prophylaxis for Post-traumatic Stress Disorder

Primary Outcomes

• Frequency of intrusive memories Three weeks

  The number of intrusive memories of the experimental model trauma film experienced. The number of intrusive memories will be recorded in a diary by participants.

• Emotional valence of intrusive memories Three weeks

  The emotional valence will be recorded in a diary after experiencing an intrusive memory in an integer scale. The integer scale will range from 1 to 10, where 1 indicates the lowest and 10 indicates the highest.

• Personal significance of intrusive memories Three weeks

  Personal significance of intrusive memories will be recorded in a diary after experiencing an intrusive memory in an integer scale. The integer scale will range from 1 to 10, where 1 indicates the lowest and 10 indicates the highest.

• Oscillatory delta power in the sleep electroencephalogram (EEG) during non rapid eye movement (REM) sleep stages N2 and N3 Four nights, each night a week apart, spanning one month

  Power in units microvolts squared will be quantified by fast Fourier transform in 4 second segment length in EEG sleep recordings in the delta frequency bin (0.5 - 4.5 Hz).Higher value of delta power indicates greater homeostatic sleep pressure, i.e., the feeling of need for sleep.

• Oscillatory theta power in the sleep electroencephalogram (EEG) during non rapid eye movement sleep stages N2 and N3 Four nights, each night a week apart, spanning one month

  Power in units microvolts squared will be quantified by fast Fourier transform in 4 second segment length in EEG sleep recordings in the theta frequency bin (6 - 9 Hz). Higher value of theta power indicates greater homeostatic sleep pressure, i.e., the feeling of need for sleep.

• EEG measures of sleep quality: distribution of N2 and N3 sleep stages. Four nights, each night a week apart, spanning one month

  Number of non-REM sleep stages N2 and N3. Greater number of stages N2 and N3 indicate greater homeostatic sleep pressure, i.e., the feeling of need for sleep.

• EEG measures of sleep quality: number of arousals Four nights, each night a week apart, spanning one month

  Number of arousals Arousals are defined by the American Academy of Sleep Medicine as an increase in EEG frequency at least 3 seconds in NREM sleep in alpha, theta or higher frequencies, excluding spindles; must be accompanied by a minimum of 1 second of muscle activity during REM sleep. The greater the number of arousals indicates the lower homeostatic sleep pressure is in healthy individuals. Normal number of arousals for a healthy adult is ca. 80 per 8 hour sleep episode.

• EEG measures of sleep quality: sleep onset latency Four nights, each night a week apart, spanning one month

  Sleep onset latency represents elapsed time from intention to initiate sleep until sleep is initiated (defined as the occurrence of any stage of sleep by the AASM). Longer latencies indicate lower homeostatic sleep pressure or some maladaptive, e.g., rumination, stress, or pathological state, e.g., insomnia, posttraumatic stress. Normal latencies for healthy adults is 10 - 20 minutes.

• EEG measures of sleep quality: sleep duration Four nights, each night a week apart, spanning one month

  Sleep duration represents the duration in time of a sleep episode excluding any intervening stages of waking. Typical sleep duration in the healthy adult population is ca. 8 hours. Extreme sleep durations (\<5 or \<6 hr or \>10 hr) have been associated with cardiometabolic illness risk.

• EEG measures of sleep quality: sleep efficiency Four nights, each night a week apart, spanning one month

  Sleep efficiency represents how efficient a given sleep episode is and is defined as the duration of sleep (i.e., time spent in all NREM and REM sleep stages) divided b by the total time spent in bed and multiplied by 100. Normal sleep efficiency is 80% or greater. Efficiencies less than this value could raise questions of sleep satiety, maladaptive behavior (e.g., alcohol consumption, caffeine consumption, sleep at incongruent circadian phase) or pathological health conditions (e.g., restless legs, disordered breathing, insomnia).

Secondary Outcomes

• Physiological stress: circulating cortisol Four nights, each morning a week apart, spanning one month

  Cortisol (nmol/l) is a marker of stress activation and will be quantified by salivary assay. Greater values indicate greater stress response. Salivary cortisol concentrations vary by sex; in males it ranges under normal conditions from 1-50 nmol/l.

• Physiological stress: electrocardiogram (ECG) heart rate (HR) Four nights, each night a week apart, spanning one month

  Average resting ECG HR during waking in healthy adult males is 75 bpm (range: 60 - 100 bpm). Higher HR from an individual's baseline HR during and after experimental model trauma will be indicative of increases in sympathetic activation of heart function.

• Physiological stress: respirometry respiration rate Four nights, each night a week apart, spanning one month

  Resting respiration rate of an adult male is 12 - 16 breaths per minute. Increases in the number of breaths per minute will indicate increase in sympathetic activation of the autonomic system.

• Physiological stress: electrocardiogram (ECG) heart rate variability (HRV) Four nights, each night a week apart, spanning one month

  Heart rate variability will be quantified by measuring inter-beat intervals of the ECG. The normal-to-normal interval will be taken, which is the interpolated interval between normal R peaks of the QRS wave complex of the ECG. HRV values indicate performance of the autonomic nervous system in a given context. Higher values of sympathetic activation will be expected during experimental model trauma film exposure.

• Physiological stress: inflammatory immune factors (cytokines and kynurenines) Four mornings, each morning a week apart, spanning one month

  Lower concentration values of immune factors will be expected in GHB or DMTN conditions compared to placebo conditions.

• Subjective ratings of mood: Positive and Negative Affect Scale (PANAS) Four nights, each night a week apart, spanning one month

  The PANAS scale assesses affect and is comprised of a positive affect subscales and a negative affect subscale. The range of scores of either are 10 - 50. Higher scores in the positive subscale indicate higher (i.e., "better") mood; lower scores in the negative affect subscale indicate lower (i.e., "worse") mood. Mean (i.e., scores for normal healthy adults) respective scores for the positive and negative subscales are 33.3 (standard deviation \[SD\] = 7.2) and 17.4 (SD = 6.2).

• Subjective ratings of mood: State Trait Anxiety Inventory (STAI) Four nights, each night a week apart, spanning one month

  The STAI assesses anxiety and is composed of a state and a trait scale. Scores in either can range from 20 - 80, and higher scores indicate greater anxiety. Mean scores for healthy adult males of the state and trait scales are, respectively 35.7 (SD = 10.4) and 34.9 (SD = 9.2).

• Awakening response: cortisol Four mornings, each morning a week apart, spanning one month

  Salivary cortisol samples will be taken at regular intervals each morning in the lab to assess the awakening response. Higher values of cortisol concentrations indicate an stronger signal in this process of gaining alertness after sleep.

• Awakening response: Psychomotor Vigilance Task (PVT) Four mornings, each morning a week apart, spanning one month

  To assess behavioral response to awaking after sleep, a simple 10 minute reaction time task at the computer called the PVT will be administered. Typical reaction times for an adult are \< 500 ms from stimulus presentation. Higher values will be expected for greater degree of sleep inertia after awakening.

• Sleep inertia Questionnaire - Acute (SIQ - Acute) Four mornings, each morning a week apart, spanning one month

  The SIQ - Acute assesses the subjective experience of the process of regaining alertness after waking from a sleep episode. Scores range from -66 to +66, higher scores indicating greater difficulty in regaining normal levels of alertness.