NLP SNP

Report for SNP rs4680

Developed by Shray Alag, 2020.

SNP Clinical Trial Gene

There are 8 clinical trials

Clinical Trials

1 The Impact of Supplementation With Multi-vitamins/Minerals, With and Without Fatty Acids, on Impulsivity and Aggression

There is a series of well designed studies that have reported, in those with a history of anti-social behavior, that supplementation with vitamins / minerals, omega-3 fatty acids (n-3 FA), or both, reduces the incidence of aggressive behavior. Although there is evidence that all these nutrients have a role, to date the relative contribution of fatty acids and vitamins / minerals has not been considered: for example the possibility of a synergistic interaction has not yet been examined. In addition the topic has to date been studied under real-life condition, such as a prison, making the topic difficult to study. The major aim of the present study was to develop a paradigm that would allow the study of the topic in a sample from the general population without a history of anti-social behavior. Subjects received either a vitamin/mineral supplement, a fatty acid supplement, both or neither for three months, Measures of impulsivity and aggression were assessed before and after supplementation. Although in the past measures of actual behaviour have proved to be sensitive to supplementation, questionnaire measures have not. The second major objective was therefore to consider whether such phenomena can be studied in a sample without a history of anti-social behavior, using standardized, sensitive laboratory based measures and to compare these with questionnaire measures. POLYMORPHISMS AND THE RESPONSE TO MICRO-NUTRIENT SUPPLLMENTATION The data set were subsequently used to test an a priori hypothesis not related to the initial hypothesis. A meta-analysis found a consistent pattern that micro-nutrient supplementation improved mood (Long SJ, Benton D. Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: a meta-analysis. Psychosom Med 2013; 75: 144-153). To produce evidence of possible mechanisms the extent was determined, to which the impact of micro-nutrient supplementation was influenced by a range of polymorphisms associated with neurotransmitter systems known to modulate mood. The primary outcome measure was the General Health Questionnaire, a 30-item self-report questionnaire that was developed to detect, in a community sample, those who would benefit from seeing a psychiatrist. Given the literature that relates polymorphisms to mood disorders, and the known pharmacology of anti-depressant drugs, a range of polymorphisms were chosen associated with serotonin and catecholamines. Dopamine The SNPs associated with the metabolism and functioning of dopamine were: Dopamine beta hydroxylase (DBH, rs16111115); Dopamine transporter (DAT1, rs2550946); Catechol-O-methyltransferase (COMT, rs4680, rs6269). Dopamine receptor D1 (DRD1, rs4532); Dopamine receptor D2 (DRD2, rs1079598, rs1800497); Dopamine receptor D3 (DRD3, rs6280); Dopamine receptor D4 (DRD4, rs1800955). Serotonin Ten SNPs associated with different aspects of serotonin metabolism were also considered. Rs1843809 is a SNP of the TPH2 gene that encodes Tryptophan hydroxylase. Rs1050565 is a SNP in the BLMH gene that influences the activity of 5HTT (SLC6A4), the serotonin transporter. SNPs associated with various serotonin receptors were also examined: genetic variations of the HTR1A gene (5-HT1A receptor, rs6295); HTR1B gene (5-HT1B receptor, rs6296); HTR2A gene (5-HT2A receptor, rs6311); HTR2B gene (5-HT2B receptor, rs1549339); HTR2C gene (5-hydroxytryptamine receptor 2C, rs518147); HTR3A gene (5-hydroxytryptamine receptor 3A, rs1150226); HTR3B (5-HT3B receptor, rs1672717); HTR4 gene (5-HT4 receptor, rs2278392). Adrenergic mechanisms Finally six SNPs associated with adrenergic receptors were considered: ADRA2A (adrenoceptor alpha 2A, rs553668); ADRB1 (adrenoceptor alpha B1, rs1801253); ADRB2 (adrenoceptor alpha B2, rs1042713; ADRB3 (adrenoceptor alpha B3, rs4994); SLC6AC (noradrenaline transporter, rs5569 and rs2242447). Analysis The data will be analyzed using analysis of variance with a change in GHQ from before to after supplementation as the dependent variable: Micronutrient/placebo X Polymorphism.

NCT01558193 Aggression Dietary Supplement: Placebo Dietary Supplement: Multi-vitamin/mineral Dietary Supplement: Docosahexaenoic acid Dietary Supplement: DHA plus vitamins/minerals

MeSH:Aggression Impulsive Behavior

HPO:Aggressive behavior Impulsivity

Dopamine The SNPs associated with the metabolism and functioning of dopamine were: Dopamine beta hydroxylase (DBH, rs16111115); Dopamine transporter (DAT1, rs2550946); Catechol-O-methyltransferase (COMT, rs4680, rs6269).

Primary Outcomes

Description: The GoStop Impulsivity Paradigm measures the ability to inhibit an already initiated response. A number of five digits are presented on a computer screen for 500ms followed by a 500ms blackout. A second number then appears for 500ms followed by a 500ms blackout. If the numbers are identical the mouse button has to be pressed before the second number disappeared. However, the response has to be with-held if a "Stop" signal appeared; that is the second number was identical but changed from black to red. If the two numbers were different then no response was required.

Measure: Go Stop Impulsivity Paradigm

Time: Change from before to after supplementation for three months

Description: This is test of the tendency to respond in an aggressive manner. A series of cartoons are presented that present an intentionally frustrating situation. The participant reports what he or she would say in that situation. Blind the responses are assessed in terms of the extent to which the responses are aggressive in matter Note that the use of two primary outcomes reflects the aim of the study to contrast performance and questionnaire measures

Measure: Rosenzweig Picture Frustration Test

Time: Change from before to after supplementation for three months

Secondary Outcomes

Description: The Buss-Perry Aggression Questionnaire assesses four aspects of aggressive behavior: physical aggression, verbal aggression, anger and hostility. Participants rank statements about their temperament using a 7-point Likert scale ranging from 1 (extremely uncharacteristic of me) to 7 (extremely characteristic of me).

Measure: Buss Perry Aggression Scale

Time: Change from before to after supplementation for three months

Description: The Perceived Stress Scale assesses the extent to which stressful thoughts and feeling had been experienced during the last month. For example: "In the last month, how often have you been upset because of something that happened unexpectedly?" The participant responded on a scale ranging from 0 = Never to 4 = Very Often. An overall score is calculated.

Measure: Perceived Stress Scale

Time: Change from before to after supplementation for three months

Description: A measure of the subjects ability to forgo initial reward for a later larger reward. The subject can choose to wait for a reward and get more points or alternatively respond more quickly and get fewer points sooner. The longer a subject waits the higher the reward; that the more points are earned. A mouse click began the task and a second resulted in a reward. Two counters display the most recent and cumulative reward over a 20 minute session. Subject are able to infer that responses at a faster rate earn smaller rewards.

Measure: Single Key Impulsivity Paradigm

Time: Change from before to after supplementation for three months

Description: Polymorphisms associated with the metabolism and receptors of dopamine and serotonin will be related to the response to micro-nutrient supplementation

Measure: General Health Questionnaire

Time: Further analysis of existing data - considers changes from baseline to three months

2 A Longitudinal Study on the Trainability of Socio-affective and Cognitive Functions and Abilities.

The purpose of the study is to look at the long term effects of a complex socio-affective mental training program on a neuroscientific-, hormonal-, behavioral-, biological, and subjective measures-level. The training protocol consists of a variety of meditation and other mental health techniques, which are trained over the period of 3-9 months (13 weeks per Module; 1-3 Modules)

NCT01833104 Healthy Subjects Behavioral: Presence - Perspective - Affect Behavioral: Presence - Affect - Perspective. Behavioral: Affect

Polym., RS1 and RS3 oxytocin-receptor gene; rs53576 catechol-O-methyltransferase gene, rs4680 serotonin-transporter 5HTTPLR gene (SCL6A4, S/L Allele and rs25531) monoamine-oxidase A gene (rs6323) mu-opioid-receptor gene (rs6323) neuropeptide Y (NPY); rs5573, rs5574, rs16139, rs16147 tryptophan hydroxylase-2 gene (rs4570625) Gene for a-subunit of L-type calcium channel Cav1.2;

Primary Outcomes

Description: Each structural MRI session has ca. 27-30 min of scan time. Investigation of long-lasting changes in cortical and sub-cortical networks after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in several structural MRI measures (MRI-based cortical thickness, mprage; T1-mapping, mp2rage; automatic amygdala volumetry; tensor-based morphometry, Diffusion Tensor Imaging; Flair)

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: The measure is part of the MRI session and lasts for ca. 15-25 min. Goal is the Investigation of dynamic changes of functional MRI signals during affective and cognitive tasks in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects. All cohorts: after T0 only "Generation" part of paradigm. TC1, TC2 and RCC1: not assessed at T1.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: Regulation and Generation of Emotions (RAGE)

Time: TC1, TC2, RCC1: Changes from T0 to T2 (T0 + 26 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months);

Description: The measure is part of the MRI session and lasts for ca. 7 min. Goal is the Investigation of dynamic changes of functional MRI signals during resting state in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: Resting State measurement

Description: The measure is part of the MRI session and lasts ca. 15 min. Goal is the Investigation of dynamic changes of functional MRI signals during affective tasks in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: Emotional Anticipation (EmoAnt)

Description: The measure is part of the session and lasts ca. 20 min. Goal is the Investigation of dynamic changes of functional MRI signals during a pain perception task in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: Modulation of pain perception

Description: The measure is part of the MRI session and lasts 15 min. Goal is the Investigation of dynamic changes of functional MRI signals during an attention and orienting task in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: Cued flanker task (CueFla), an attention and orienting task

Description: The measure is part of the MRI session and lasts ca. 35-40 min. Goal is the Investigation of dynamic changes of functional MRI signals during a theory of mind and social cognition task in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: a Theory of Mind and Social Cognition task (the EmpaToM)

Description: ] Examination of the diurnal cortisol profile (awakening, day timeline): on two weekdays, subjects collect saliva samples during the day (7 timepoints, each ca. 3 min). This will be coordinated with the experience sampling via the smartphones.

Measure: Changes in stress physiology: "diurnal cortisol profile"

Description: People sit quietly and no specific task given. We will use "Biopac MP150 Bionomadix" for measurement of autonomic activity (inferred from heart rate variability) by measuring a 3-point ECG in the chest area, as well as electrodermal activity (on the fingertips of the left index and middle finger), and breathing.

Measure: Changes in autonomic nervous system functions: Physiological Resting Baseline (electrocardiogram (ECG), electrodermal activity (EDA), and breathing)

Description: Part of the Virtual Reality Session (ca. 40 min): In a virtual world, we will look at attention and change detection in an unknown environment with emotional stimuli. It will happen on the same day as the MRI measurements and will be measured by counting the amount of changes of the virtual environment that could be detected. Behavioral measures will be combined with physiological data assessment during the test.

Measure: Changes in a Virtual Reality Setting: The Panopticon --> attention and change detection

Description: Part of the Virtual Reality Session (ca. 40 min): In a virtual world, we will look at changes in social distance. It will happen on the same day as the MRT measurements and will be measured by detecting the preferred proximity to avatars within the virtual worlds. Behavioral measures will be combined with physiological data assessment during the test.

Measure: Changes in a Virtual Reality Setting: The Crowded Room --> changes in social distance to avatars

Description: Part of the Virtual Reality Session (ca. 40 min): In a virtual world, we will look at changes in approach and avoidance behavior in terms of affective preferences of available affective stimuli. It will happen on the same day as the MRT measurements and will be measured by detecting the amount of exploratory behavior (approaching, examining objects with neutral or emotional content). Behavioral measures will be combined with physiological data assessment during the test.

Measure: Changes in a Virtual Reality Setting: The Affect Gallery --> changes in affective preferences

Description: Part of the Virtual Reality Session (ca. 40 min): In a virtual world, we will look at changes in acute stress reactions to aversive affective stimuli (e.g., ground shaking, bugs, sudden loud noise, angry avatars). It will happen on the same day as the MRT measurements. Behavioral measures will be combined with physiological data assessment during the test.

Measure: Changes in a Virtual Reality Setting: Room 101 --> acute stress reactions

Description: In this task, two stimuli are presented consecutively (e.g., a pattern with horizontal lines). The two stimuli differ slightly and the participants are asked to identify the differences (e.g., length or direction of the lines). The difference between the two stimuli gradually decreases with each round. The point, at which the participants cannot distinguish between the two stimuli is called the perceptional sensitivity. After each round, the participants are asked to assess their level of certainty regarding their answers. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the Inhibition and Alerting task (Stop-Signal-Reaction Time task).

Description: The participants are presented with 4, 6 or 8 letters, which they have to remember over a short period of time (about 2 seconds). Then they are presented with another letter and are asked to state whether or not that letter was part of the set of letters presented beforehand. After each round, the participants are asked to assess their level of certainty regarding their answers. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in Working Memory Performance

Description: The cognitive and affective flexibility is measured in this task. Participants are asked to complete comparable cognitive and affective task-switching tasks respectively. We use a task-cueing paradigm in which participants have to judge different stimuli. These stimuli are cognitive or affective in nature. The dependent variable is reaction time and accuracy in so-called "shift" or "no-shift" rounds, i.e. rounds which either have the same task as the round before ("no-shift") or rounds, which consist of a new task ("shift"). All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the Task Emotional Switching Paradigm

Description: Participants are asked to judge the similarity of a number of adjectives which describe emotional states. Using network analysis and multi-dimensional scaling, the data regarding the proximity of the adjectives are transformed in a depiction of the emotional-concept networks of the participant. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the Emotional Granularity task

Description: Participants watch a number of short clips (max. 15 sec) of news programs or documentaries. These clips have either neutral or have emotional (negative) content. After watching a clip participants report on their emotional state and on how much compassion they feel. Additionally, we will use physiological data assessment of the following parameters during the task: respiration frequency (belt in the chest / abdominal area) heart rate (3-point ECG in the chest area) EDA

Measure: Changes in autonomic nervous system functions and computer experiment: Changes in the Socio-affective Video Task (SoVT)

Description: In this computer-based task, participants see a person standing in a room, in which oval-shaped objects can be seen on the walls. The participants are asked to report on how many of these objects can be seen from their own perspective and how many objects the person in the room is able to see. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Visual Spatial Perspective Taking Task" by Samson

Description: In this task, a number of visual stimuli are presented consecutively for short periods of time (about 100ms). The relevant stimuli are embedded in a number of distractor-stimuli. The participants are asked to report on the number of perceived relevant stimuli. They are also supposed to identify them. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Emotional Attentional Blink" paradigm

Description: In this computer-based game, participants have to find their way through a labyrinth and solve little tasks on their way. They are under the impression, that there is another participant playing with them. The participant's readiness to share resources, necessary to complete the game, is measured. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Trust Game"

Description: There are two parts to this game: 2nd person punishing and 3rd person punishing. In the 2nd person punishing game, there are two players. One Player (player A) has a larger amount of money at her disposal, than the other player (player B). The player with the larger amount of money can decide how she wants to split the money between herself and the other player. Then player B can decide whether he wants to punish player A by taking money from player A while using his own money (for each unit of money she spends three three units are taken from the other player). After two rounds, the tasks of the players are reversed. In the 3rd person punishing game, the participants watch the interaction of anonymous players A and B. After each round, the participant can decide whether or not to punish the player, who split the money. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Punishing Game"

Description: In this game, participants can decide how they split a set amount of money between themselves and an anonymous player. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Dictator Game"

Description: In a first step, participants are asked to cluster 30 positive or negative personality traits around their depicted self in such a way, that the spatial closeness or distance reflects, how much they identify with the trait. In a second step, they are asked to choose selected items and pile them. The height of the stack then is thought to reflect the complexity of the self. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Self-complexity Task"

Description: In the first part of this task, participants are asked to judge adjectives regarding a) whether they apply to themselves, b) whether they apply to a famous person (e.g., Angela Merkel), or c) whether they meet linguistic criteria (e.g., whether they are written in capital letters). In the second part, participants are asked to identify the adjectives, which had been presented in the first part. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: "Self-reference Task"

Description: Aim of this measure is to access the amount and content of spontaneously generated cognition. Main focus is "day dreaming" or "mind wandering" that occurs, when our minds drift off, while working on a task. In this measure, subjects are asked to work on two little, rather boring PC-based exercises (1. choice reaction time task (CRT); 2. working memory (WM) task). During selective queries, they are then asked for the content and valence of their thoughts ("thought probe"). All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Mind-wandering task"

Description: This economic game assesses the participant's willingness to donate to selected charity groups. In this game, they receive a certain amount of money and can decide, if and how much they would like to contribute. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in "Donation Task"; willingness to make donations in the economic computer experiment.

Description: Participants divide money between themselves and close friends, strangers, or enemies. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: "Social Discounting" Task

Description: Subjects are asked to silently count their heart beats in five intervals [15, 25, 35, 45, 55], presented in a random order, and note the counted number.

Measure: Changes in interoception: Heart Beat Perception Task

Description: Local Power (LP), as short term estimate of high frequency heart rate variability is reported to the subjects. They observe a ball on a computer screen, which ascends in accordance with their LP. Goal is to make the ball rise. We will use the "Biopac MP150 Bionomadix" for measurement of respiration frequency (belt in the chest / abdominal area) as well as ECG and electrodermal activity.

Measure: Changes in autonomic nervous system functions: Local Power Biofeedback and Heart Rate Biofeedback

Description: TSST: a standardized stress test, that induces stress in the laboratory. Here, cortisol and alpha-amylase are analyzed from saliva (Department of Biological and Clinical Psychology, Trier University), oxytocin (Max-Planck-Institute for Psychiatry, Munich) as well as the inflammatory markers Interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and C-reactive protein (CRP) are analysed from blood (Aghia Sophia Children's Hospital, Department of Clinical Biochemistry) and heart rate and heart rate variability (HRV) are assessed as adjunct measurement. Stress-related questionnaires will be filled out during the TSST as well.

Measure: Stress Physiology: "Trier Social Stress Test" (TSST)

Time: Because it includes elements of deception, the TSST is only done once: Participants will either do the TSST at T0, T1, or T2

Description: Heart rate, body movement,respiratory frequency and heart rate variability are being measured during two meditation sessions in each training block (week 3 and 13). We use the non-invasive "Zephyr BioHarness 3 multi-sensor-device", which comes with a chest belt. After the meditation session, subjects are asked to answer a 5-item questionnaire.

Measure: Changes in autonomic nervous system functions: "Physiological Signature of Meditation states"

Time: Only in TC1, TC2, TC3: Changes from T1, to T2, to T3; week 3 and 13 of each module.

Description: During each measurement time point, blood samples will be collected from each subject and stored at -80 degrees Celsius. The aim is to test if the training leads to reduced shortening of the telomeres, the probes are sent to the Blackburn lab of UCLA in San Francisco, USA. Additionally, a complete blood count is drawn. Not aiming in diagnostic directions, the goal is to assess the status of neutrophils, lymphocytes, and monocytes in the probes. These are thought to be general markers of immune activity and are inspected in relation to telomere length. Blood counts will be assessed by a lab in Leipzig, Germany.

Measure: Changes telomere length (+ number of neutrophils, lymphocytes, and monocytes)

Description: Once during the training for each subject, before and directly after a 2h "Perspective" or "Affect" training session, a blood sample will be drawn and stored at -80 degrees celsius. To analyze blood levels of oxytocin, probes are sent to the Max-Planck-Institut für Psychiatrie, Munich, Germany (Department of Prof. Rainer Landgraf). The same procedure was done pre and post the TSST session.

Measure: Training induced short-term changes in oxytocin blood level (pre/post Meditation)

Time: Changes pre/post a "Perspective" or "Affect" training session during T1, T2, or T3; Week 12 of Training (i.e. for arm one: between 11/21/13 - 12/23/13 or 3/3/14 - 4/5/14; for arm two: between 1/20/14 - 2/20/14 or 5/2/14 - 5/24/14). Pre/Post TSST

Description: 10 ml blood samples will be drawn. Plasma levels of interleukin-6, brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP) will be assessed. They are sent to the "First Dept of Pediatrics, Director, Division of Endocrinology, Metabolism and Diabetes, University of Athens Medical School, Aghia Sophia Children's Hospital, Athens, Greece" for analysis.

Measure: Changes in amount of plasma levels (blood samples) of interleukin-6, brain-derived neurotrophic factor, C-reactive protein.

Description: All cohorts: • weekly questions via online platform, concerning: actual affective condition, actual activity, actual thoughts, social closeness, quality of sleep (administered once a week via short questions online, duration 2-4 min.). TC1, TC2, TC3: • questions via online platform before and after all core training exercise participants perform at home; duration is ca. 2-4 min, concerning: actual effects and experiences after daily mental training practice. All cohorts: • experience- sampling via smartphones, concerning: valance and arousal of current emotional state using "single item affect grid" method. Current activity and situation. Current thoughts. Amount of significant or stressful events since last sampling and how positive or negative or stressful was this event. How did you cope with this event. (7-10 times for 2 consecutive days for each cohort at T0-T4).

Measure: Changes in "subjective experience sampling by smartphones or by means of an internet platform"

Secondary Outcomes

Description: above: w=weeks, m=months. Administration of the questionnaire via an online platform. It assesses effortful control, extraversion, frustration, inhibitory control, negative affect, sadness, sociability, etc. TC1 and TC2 participants will not fill out the questionnaire at time point T2.

Measure: Questionnaire: Changes in "Adult temperament questionnaire (ATQ)"

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2 (T1 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 or 10 m).

Description: Administration of the German questionnaire via an online platform. It assesses symptoms of attentional deficits, attention deficit hyperactivity disorder (ADHD), hyperactivity.

Measure: Questionnaire: Change in "ADHS-Selbstbeurteilungsfragebogen (ADHS-SB)".

Description: Administration of the questionnaire via an online platform. It assesses non-judgmental acceptance of experience, awareness of experience, and mindfulness.

Measure: Questionnaire: Change in "FFA Freiburger Fragebogen zur Achtsamkeit".

Description: Administration of the questionnaire via an online platform. It assesses awareness, describing, non-judging of experiences, non-reactivity, observing, mindfulness. This questionnaire is also filled out by the observers of participants.

Measure: Questionnaire: Change in questionnaire "Five Facets Mindfulness Questionnaire (FFMQ)".

Description: Administration of the questionnaire via an online platform. It assesses different facets of interoceptive awareness.

Measure: Questionnaire: Change in "Multidimensional Assessment of Interoceptive Awareness (MAIA)".

Description: Administration of the questionnaire via an online platform. It assesses self-compassion, self-kindness, self-judgment, over-identification, mindfulness, isolation, and common humanity.

Measure: Questionnaire: Change in "Self-Compassion Scale" by Kristin Neff (SCS).

Description: Administration of the questionnaire via an online platform. It assesses serenity, i.e. low arousal positive affect. TC1 and TC2 participants will not fill out the questionnaire at time point T2 and T3.

Measure: Questionnaire: Change in "The Short Affect intensity scale (only serenity subscale) (SAIS)".

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w), to T4 (T3 + 4.5 or 10 m). RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2 (T1 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 or 10 m). w=weeks; m=months

Description: Administration of the questionnaire via an online platform. It assesses compassion for others, common humanity, disengagement, indifference towards others, kindness towards others, mindfulness, separation.

Measure: Questionnaire: Change in "Compassion scale - How I typically act towards others (COSN)".

Description: Administration of the questionnaire via an online platform. It assesses empathic concern, empathic distress and ability to take other's perspective. This questionnaire is also filled out by observers of the participants.

Measure: Questionnaire Participants and Observer: Change in "Interpersonal Reactivity Index (IRI)".

Description: Administration of the questionnaire via an online platform. It assesses active, reactive and safe/warm positive affect.

Measure: Questionnaire: Change in "Types of Positive Affect (TTPAS)".

Description: Administration of the questionnaire via an online platform. It assesses fear of compassion from others or for self.

Measure: Questionnaire: Change in "Fears of Compassion Scales (FOCS)".

Description: above: w=weeks, m=months Administration of the questionnaire via an online platform. It assesses impulsivity, affective instability, relationships, abandonment, quasi-psychotic states, self image, emptiness, anger, suicide, borderline personality traits. TC1 and TC2 participants will not fill out the questionnaire at time point T2.

Measure: Questionnaire: Change in "Borderline Personality Questionnaire (BPQ)".

Description: above: w=weeks, m=months Administration of the questionnaire via an online platform. It assesses narcissism, exhibitionism, entitlement, authority, superiority, exploitativeness, self-sufficiency, vanity. TC1 and TC2 participants will not fill out the questionnaire at time point T2.

Measure: Questionnaire: Change in "Narcissistic Personality Inventory (NPI)".

Description: Administration of the questionnaire via an online platform. It assesses regulation via catastrophizing, positive refocusing, or blaming others strategy (self-blame, acceptance, rumination, positive refocus, planning refocus, planning refocus, positive reappraisal, perspective, catastrophizing, other blame)

Measure: Questionnaire: Change in "Cognitive Emotion Regulation Questionnaire (CERQ)".

Description: above: w=weeks, m=months, T2 (T1+ 13 weeks), T3 (T2 + 13 weeks) Administration of the questionnaire via an online platform. It assesses several coping strategies. TC1 and TC2 participants will fill out a shorter version at time point T2 and T3. This questionnaires is also filled out by observers of participants.

Measure: Questionnaire Participants and Observers: Change in "Brief COPE" inventory.

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w) and at T4 (T3 + 4.5 or 10 m). Short version at T2 and T3; RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2, to T3, to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 o

Description: Administration of the questionnaire via an online platform. It assesses expressivity of negative and positive emotions, and strength of expression impulse. TC1 and TC2 participants will not fill out the questionnaire at time point T2 and T3.

Measure: Questionnaire: Change in "Berkeley Expressivity Questionnaire (BEQ)".

Description: Administration of the questionnaire via an online platform. It assesses range of experience emotions, and differentiation of experienced emotions.

Measure: Questionnaire: Change in "Range and Differentiation of Emotion Scale (RDEES)".

Description: Administration of the questionnaire via an online platform. It assesses tendency to choose decisions that maximize other's output.

Measure: Questionnaire: Change in "An Instrument to Measure Social Value Orientation (SVO) " by van Lange et al.

Description: Administration of the questionnaire via an online platform. It assesses internally focussed emotion regulation of positive and negative affect. TC1 and TC2 participants will not fill out the questionnaire at time point T2 and T3.

Measure: Questionnaire: Change in "Emotion Regulation of Others and Self (EROS)".

Description: Administration of the questionnaire via an online platform. It assesses compassionate and self-image goals.

Measure: Questionnaire: Change in "Friendship, Compassionate and Self-Image Goals Scale".

Description: Administration of the questionnaire via an online platform. It assesses the degree to which people's self-concepts center on moral traits.

Measure: Questionnaire: Change in "Self Importance of Moral Identity Scale".

Description: Administration of the questionnaire via an online platform. It assesses global awareness and understanding of others and attempts and endeavours to understand the perspective ot others.

Measure: Questionnaire: Change in "Self Dyadic Perspective-Taking Scale and Other Dyadic Perspective Taking Scale (SDPT /ODPT )".

Description: Administration of the questionnaire via an online platform. It assesses the tendency to perceive oneself as interdependent with others or as an independent person.

Measure: Questionnaire: Change in "Self Construal Scale".

Description: Administration of the questionnaire via an online platform. It assesses the tendency to behave in a prosocial way (help and support others). This questionnaire is also filled out by observers of participants.

Measure: Questionnaire Participants and Observers: Change in "Prosocialness Scale" by Capara.

Description: Administration of the questionnaire via an online platform. It assesses self reported self attitudes using an open-ended response format beginning with: "Who am I...".

Measure: Questionnaire: Change in "Twenty Statement Test (TST)".

Description: Administration of the questionnaire via an online platform. It assesses tendency to value own advantage over moral principles.

Measure: Questionnaire: Change in "The Machiavellianism Scale".

Description: Administration of the questionnaire via an online platform. It assesses personality traits such as neuroticism, extraversion, openness, agreeableness, conscientiousness, aesthetic interests, negative affect, sociability, etc.

Measure: Questionnaire: Change in "NEO Fünf Faktoren Inventar (NEO FFI)".

Description: Administration of the questionnaire via an online platform. It assesses rumination, magnification and helplessness regarding pain.

Measure: Questionnaire: Change in "Pain Catastrophizing Questionnaire (PCS)".

Description: Administration of the questionnaire via an online platform. It assesses uncertainty intolerance, paralysis by uncertainty, negative affect by uncertainty and increased vigilance by uncertainty.

Measure: Questionnaire: Change in "Unsicherheitstoleranz-Skala (Uncertainty Intolerance, UI-18)".

Description: Administration of the questionnaire via an online platform. It assesses work dissatisfaction, excessive demands at work, lack of social recognition, social isolation, chronic concern, chronic stress, and social tensions etc.

Measure: Questionnaire: Change in "Trier Inventory for Chronic Stress (TICS)".

Description: Administration of the questionnaire via an online platform. It assesses the degree to which situations in one's life are appraised as stressful.

Measure: Questionnaire: Change in "Perceived Stress Scale (PSS-10)".

Description: Administration of the questionnaire via an online platform. It assesses paternal and maternal care and overprotection.

Measure: Questionnaire: Change in "Parental Bonding Inventory (PBI)".

Time: TC1, TC2, RCC1, RCC2, TC3: T0 only

Description: Administration of the German questionnaire via an online platform. It assesses general well-being, tiredness, emotional reactivity, sensory problems, gastrointestinal problems, nose/throat irritation, tension, pain, and cardiovascular problems.

Measure: Questionnaire: Change in "Freiburger Beschwerdeliste (FBL)".

Description: Administration of the questionnaire via an online platform. It assesses sleep habits and sleep quality.

Measure: Questionnaire: Change in "Pittsburgh Sleep Inventory (PSQI)".

Description: Administration of the questionnaire via an online platform. It assesses hope for success and control, fear of rejection and failure or losing control, and hope for affiliation.

Measure: Questionnaire: Change in "Multi Motive Grid (MMG)".

Description: Administration of the questionnaire via an online platform. It assesses overall psychological well-being, emotional and social well-being, etc.

Measure: Questionnaire: Change in "Mental Health Continuum short form (MHC-SF)".

Description: Administration of the questionnaire via an online platform. It assesses satisfaction with one's life. This questionnaire is also filled out by observers of participants.

Measure: Questionnaire Participants and Observers: Change in "Satisfaction with Life Scale (SWLS)".

Description: Administration of the questionnaire via an online platform. It assesses severity of depression, affective and somatic symptoms of depression.

Measure: Questionnaire: Change in "Becks Depression Inventory (BDI-2)".

Description: Administration of the questionnaire via an online platform. It assesses ego-resiliency.

Measure: Questionnaire: Change in "Ego Resiliency Scale (ER-89)".

Description: Administration of the questionnaire via an online platform. It assesses anxiety and avoidance. TC1 and TC2 will not fill out this questionnaire at time point T2 and T3.

Measure: Questionnaire: Change in "Experiences in Close Relationships - revised (ECR-RD)".

Description: Administration of the questionnaire via an online platform. It assesses lonliness.

Measure: Questionnaire: Change in "UCLA Lonliness Scale".

Description: Administration of the questionnaire via an online platform. It assesses positive and negative affect in the last weeks.

Measure: Questionnaire: Change in "Positive Affect Negative Affect Schedule (PANAS)".

Description: Administration of the questionnaire via an online platform. It assesses positive and negative emotions. This questionnaire was assessed on a weekly basis.

Measure: Questionnaire: Change in "modified Differential Emotions Scale (mDES)".

Time: Weekly; TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses difficulties in identifying and describing emotions, as well as an externally oriented thinking style.

Measure: Questionnaire: Change in "Toronto Alexithymia Scale (TAS-20)"

Description: Administration of a paper & pencil version of the POMS mood scale, for each subject on that day, when they do the TSST stress test. It assesses mood states.

Measure: Questionnaire: Change in "Profile of Mood States - 2nd Edition (POMS-2)".

Time: Only once per participant during the TSST

Description: Administration of a paper & pencil version, for each subject on that day, when they do the TSST stress test. It assesses state anxiety.

Measure: Questionnaire: Change in "STAI -X1 State, State Trait Anxiety Inventory".

Time: Only once per participant during the TSST

Description: Administration of a paper & pencil version of a measure for the visualisation of body sensations following Fox et al. (2012). The measure will be administered at the start and the end of the first training block, the "presence block". The start of the presence block for arm one will be: Aug. 19th 2013 till Sept. 19th 2013. The start of the presence block for arm two will be: Okt. 7th 2013 till Okt. 30th 2013.

Measure: Questionnaire: Change in "Subjective Sensory Sensitivity questionnaire" following Fox et al. (2012)".

Time: Changes during the Presence Module (beginning and end of Module).

Description: above: w=weeks, m=months; Administration of the questionnaire via an online platform. It assesses the noticing of body sensations. TC1 and TC2 will not fill out this questionnaire at time point T2

Measure: Questionnaire: Change in "Private Body Consciousness subscale of the Body Consciousness Questionnaire (PBCS)".

Description: Administration of questionnaire via online platform. The scale is answered by observers of participants only. It assesses responsiveness to partner's disclosure of positive events.

Measure: Questionnaire - Observer only: Change in "Perceived Responsiveness Scale (12 items)" filled out by observers.

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months)

Description: Administration of questionnaire via online platform. The scale is answered by observers of participants only. It assesses positive reactions of partner by several subscales.

Measure: Questionnaire - Observer only: Change in "Capitalization" by Gable et al., 2004 filled out by observers

Description: Administration of questionnaire via online platform. The scale is answered by observers of participants only. It assesses degrees to which respondent agrees with partner, do activities together, or satisfaction with partner.

Measure: Questionnaire - Observer only: Change in "Dyadic Adjustment Scale (DAS)".

Description: Administration of questionnaire via online platform. The scale is answered by observers of participants only. It assesses personality traits such as emotional stability, openness, conscientiousness, agreeableness, extraversion. This questionnaire has also been used for matching the cohorts into their respective groups.

Measure: Questionnaire - Observer: Change in "Ten Item Personality Scale (TIPI-10)"

Description: Administration of questionnaire via online platform. The scale is answered by observers of participants only. It assesses the feelings of closeness to others

Measure: Questionnaire - Observer only: Change in "Inclusion of Other in the Self Scale (IOS)"

Description: During each measurement time point, the subjects are asked for small hair samples from the back of their head. It will be sent to a cooperating lab in Dresden to assess long-term stress by analyzing the the amount of cortisol in hair samples.

Measure: Stress physiology: Changes in "Long-term cortisol levels from hair samples"

Description: Analyze the connection between gene variants, personality traits, training effects, behavior, brain activation. Arginine-vasopressin-receptor gene; microsat. Polym., RS1 and RS3 oxytocin-receptor gene; rs53576 catechol-O-methyltransferase gene, rs4680 serotonin-transporter 5HTTPLR gene (SCL6A4, S/L Allele and rs25531) monoamine-oxidase A gene (rs6323) mu-opioid-receptor gene (rs6323) neuropeptide Y (NPY); rs5573, rs5574, rs16139, rs16147 tryptophan hydroxylase-2 gene (rs4570625) Gene for a-subunit of L-type calcium channel Cav1.2; CACNA1C gene (rs1006737) Gene for a-subunit of nico. acetylch. receptor channel, CHRNA4 gene (rs1044396) Deletion mutation of a-2-beta adrenoreceptor gene Cannabinoid-receptor 1 gene (CNR1); rs6454674, rs806380, rs806377, rs1049353 Dopamine D4 Receptor gene (DRD4); rs1800955, VNTR Exon 3 repeat allele Dicarboxylate/amino acid cation sodium transporter (DAT1); rs27072, VNTR repeat allele

Measure: Assessment of gene variants / polymorphisms

Time: Blood samples are taken once during T0

Description: Administration of the questionnaire via an online platform. It assesses affiliation tendency and rejection sensitivity.

Measure: Questionnaire: Change in "Affiliation Tendency and Rejection Sensitivity Scales"

Description: Administration of the questionnaire via an online platform. It assesses self-reported fidgeting and mind-wandering behavior.

Measure: Questionnaire: Change in "Spontaneous Activity Questionnaire (SAQ)"

Description: Administration of the questionnaire via an online platform. It assesses self-reported deliberate and spontaneous mind wandering behavior.

Measure: Questionnaire: Change in "Spontaneous and Deliberate Mind Wandering Scales (MDD, MDS)"

Description: Administration of the questionnaire via an online platform. It assesses subscales of personality traits such as warmth, gregariousness, assertiveness, activity, seeking excitement, positive emotions, and extraversion.

Measure: Questionnaire: Change in "Subscales from the NEO Persönlichkeitsinventar nach Costa and McCrae - revised version (NEO-PI-R)"

Description: Administration of the questionnaire via an online platform. It assesses the tendency to respond in a socially desirable way.

Measure: Questionnaire: Change in "Soziale Erwünschtheits-Skala-17 (SES-17)"

Description: Administration of the questionnaire via an online platform. It assesses trait anxiety. It was used of screening possible participants for the study.

Measure: Questionnaire: Change in "State-Trait Anxiety Inventory (STAI-X2; STAI-Trait)".

Other Outcomes

Description: German Paper/Pencil questionnaire that assesses psychopathological occurences in family members.

Measure: Questionnaire: "Psychopathologie der Familie / Psychopathology in family members".

Time: Only once per participants at time point T0

Description: The d2 Test is a timed test of selective attention/concentration. In response to the discrimination of similar visual stimuli, the test measures processing speed, rule compliance, and quality of performance, allowing estimation of individual attention and concentration performance. It was used of matching participants into cohorts.

Measure: Questionnaire - Matching: Score of "Test d2 - Revision (d2R)" attention task.

Time: 2 months before T0 and during initial proband screening phase of the project, each subject takes the d2 test in paper & pencil version..

Description: The TIPI is designed to assess the constellation of traits defined by the Five Factor Theory of Personality. It was used of matching participants into cohorts.

Measure: Questionnaire - Matching: Score of "Ten Item Personality Inventory (TIPI-10)" personality test.

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: Administration of the questionnaire via an online platform. It assesses overall psychological well-being, emotional and social well-being, etc. It was used of matching participants into cohorts.

Measure: Questionnaire - Matching: Score of "Mental Health Continuum short form (MHC-SF)".

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Measure: Questionnaire - Matching: Score of "Compassion scale - How I typically act towards others (COSN)".

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: Administration of the questionnaire via an online platform. It assesses the degree to which situations in one's life are appraised as stressful. It was used of matching participants into cohorts. This questionnaire is also filled out by observers of participants.

Measure: Questionnaire - Matching/Observers: Score of "Perceived Stress Scale (PSS-10)".

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Measure: Questionnaire - Matching/Observer: Score of "Five Facets of Mindfulness Questionnaire (FFMQ)".

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: German Paper/Pencil Questionnaire that assesses Non-verbal Intelligence.

Measure: Questionnaire: Score of "Grundlagenintelligenztest Skala 2- Revision without WS/ZF-R" (Intelligence Test)

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: On a voluntary basis and with written consent, conducted qualitative interviews with some of the participants, where they are able to describe the subjective experience of the whole training. The interviews will be video-taped with the consent of the participants. We will be using depth-interview techniques that assess not only what the subjects experience but also how they process it. Interviews will be done by a interview specialist with a degree in Psychology and Philosophy. The data will be treated in accordance with data protection laws. In further publications, all statements of the subjects will be anonymized, the tapes will be erased after transcription. In case they agreed to be video-taped, the material will potentially be used for a video documentation of the whole ReSource Project.

Measure: Qualitative Elicitation Interviews and Interviews about subjective Experience during the study (1-2 hours)

Time: only TC1, TC2, or TC3: Voluntarily, possible during each Training Module

Measure: Questionnaire - Matching: Score in "Self-Compassion Scale" by Kristin Neff (SCS).

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: Administration of the questionnaire via an online platform. It assesses mild to severe depression. It was used of screening possible participants for the study

Measure: Questionnaire - Screening/Matching: "Major Depression Inventory (ICD-10, MDI)"

Time: Screening procedure of each participant before matching into cohorts

Description: Administration of the questionnaire via an online platform. It assesses difficulties in describing emotions, tendency to focus attention externally, alexithymia, identification of emotions. It was used of screening possible participants for the study.

Measure: Questionnaire - Screening/Matching: "Toronto Alexithymia Scale (TAS-20)".

Time: Screening procedure of each participant before matching into cohorts

Description: Administration of the questionnaire via an online platform. It assesses trait anxiety. It was used of screening possible participants for the study.

Measure: Questionnaire - Screening/Matching: "State-Trait Anxiety Inventory (STAI-X2; STAI-Trait)"

Time: Screening procedure of each participant before matching into cohorts

Description: Administration of the questionnaire via an online platform. It assesses psychological health and drug abuse. It was used of screening possible participants for the study.

Measure: Questionnaire- Screening: "Patient Health Questionnaire - D (PHQ-D)

Time: Screening procedure of each participant before matching into cohorts

Description: Interview with possible participants. It assesses psychological disorders. It was used of screening possible participants for the study.

Measure: Screening - Interview: DIA-X for Axis II psychiatric disorders of DSM-IV and clinical interviews for personality disorders (SCID-II)

Time: Screening procedure of each participant before matching into cohorts

Description: Interview with possible participants. It assesses psychological disorders. It was used of screening possible participants for the study.

Measure: Screening - Interview: DIA-X for Axis I psychiatric disorders of DSM-IV

Time: Screening procedure of each participant before matching into cohorts

3 Dexamethasone for the Treatment of Established Postoperative Nausea and Vomiting - a Randomised, Placebo-controlled, Dose-finding Study

Postoperative nausea and vomiting (PONV) are frequent after surgery and anaesthesia. Dexamethasone is widely used as antiemetic for the prevention of PONV. Little is known about the efficacy of antiemetic drugs for the treatment of established PONV symptoms. No single randomised trial has been published so far that tests the efficacy of dexamethasone for the treatment of established PONV symptoms. In this trial the investigators want to test the antiemetic efficacy of three different doses of intravenous dexamethasone for the treatment of established PONV symptoms. In adjunct protocols of this study the investigators aim to establish a novel method to quantify the anti-nausea efficacy of an antiemetic drug, to study pharmacogenetics of PONV, and to further our understanding on the smoking status as a predictive factor of PONV.

NCT01975727 Postoperative Nausea and Vomiting Vomiting Drug: Placebo Drug: Dexamethasone 3 mg Drug: Dexamethasone 6 mg Drug: Dexamethasone 12 mg

MeSH:Nausea Vomiting Postoperative Nausea and Vomiting

HPO:Nausea Vomiting

The SNP rs4680 (c.472G > A) is a missense mutation leading to a four-fold reduction of the COMT enzyme.

The COMT Val158Met polymorphism (rs4680) will be genotyped using a commercially available TaqMan® SNP genotyping assay (C_25746809_50, Applied Biosystems, Warrington, UK).

Primary Outcomes

Description: Complete absence of any nausea and/or vomiting (including retching) in a previously nauseated or vomiting patient within 24 hours after administration of the study treatment.

Measure: Treatment efficacy of Dexamethasone for established PONV

Time: 24 hour follow up

Secondary Outcomes

Description: Free from PONV during the first 6 hours

Measure: Short term efficacity

Time: 6 hours

Description: Number of patients staying PONV free after rescue antiemetic during the first 24 postoperative hours

Measure: PONV free after rescue antiemtic

Time: 24 hour follow up

Description: quality of sleep during the first postoperative night (numerical rating scale ranging from 0 = no sleep at all to 10 = excellent sleep)

Measure: Quality of sleep

Time: 24 hour follow up

Description: any minor or major adverse effects during 24h.

Measure: Minor or major adverse effects

Time: 24 hour follow up

4 Effect of COMT (Catecholamine-O-methyltransferase) Genetic Polymorphisms on Response to Propranolol Therapy in Temporomandibular Disorder

Purpose: Primary: To evaluate the efficacy of extended-release (ER) propranolol compared to placebo in the reduction of a pain index in patients with temporomandibular disorder (TMD). Secondary: To determine if extended-release propranolol efficacy varies according to participants' catechol-O-methyltransferase (COMT) genetic polymorphisms and to investigate the efficacy of extended-release propranolol compared with placebo using secondary endpoints. Exploratory: To investigate whether the efficacy of extended-release propranolol in the reduction of the pain index varies according to participants' polymorphisms in 3 other genetic regions and according to various phenotypic characteristics. Participants: 200 patients with chronic TMD will be randomly assigned, in a 1:1 parallel, double-blind fashion, to receive either extended-release propranolol or placebo at one of three study sites: University of North Carolina-Chapel Hill School of Dentistry; University of Florida-Gainesville College of Dentistry; and the State University of New York at Buffalo School of Dental Medicine. Procedures (methods): Randomization will be to either propranolol or placebo. The 10-week study treatment period is divided into: 1 week of drug titration, 8 weeks of drug maintenance, and 1 week of drug tapering. The titration and tapering doses are 60 mg (capsules) once per day orally; the maintenance dose is 60 mg twice per day orally. Participants will attend 6 clinic visits over 12-15 weeks as follows: screening and baseline visit (Visit [V] 0, 7-21 days prior to V1); randomization and start of treatment (titration) (V1, study day 0); maintenance visit 2 (V2, 1 week post-randomization, study day 7+3); maintenance visit 3 (V3, 5 weeks post-randomization, study day 35 +/- 7); tapering visit (V4, 9 weeks post-randomization, study day 63 +/- 7); and tapering visit 5 (V5, 11 weeks post-randomization and 1 week after drug tapering ends, study day 77 +/- 7). Depending on the visit, procedures will include: reviews of medical history, weekly alcohol consumption, concomitant therapies and medications, adverse events, compliance, and eligibility; administration/review of questionnaires; blood draw; pregnancy test in women of childbearing potential; and dispensing of study drug.

NCT02437383 Temporomandibular Disorders Drug: Propranolol ER Drug: Placebo

MeSH:Temporomandibular Joint Disorders Temporomandibular Joint Dysfunction Syndrome

The pain index was stratified per number of catechol-O-methyltransferase (COMT) Low Pain Sensitive (LPS) haplotypes.. Change in the Weekly Mean Pain Index After 9 Weeks of Treatment Stratified Per Number of COMT Valine Alleles at rs4680.

The pain index was stratified per number of catechol-O-methyltransferase (COMT) valine alleles at single nucleotide polymorphism (SNP) rs4680.. Inclusion: - Diagnostic criteria for TMD: Group II, Masticatory Muscle Disorders, Myalgia - Facial pain for at least 3 months (and at least 10 of the last 30 days at Visit 0) - Average pain intensity rating ≥30 (0-100 numeric rating scale) over the past week or average daily pain intensity rating ≥30 on the same scale on at least 3 days over the past week - Agrees to terms for continuing/discontinuing certain prescription/over-the-counter pain medications throughout participation - Agrees to not commence new prescription medication, injection therapy, occlusal splint therapy or certain other pain management techniques throughout participation - Agrees to limit consumption of alcohol to no more than 7 drinks/week (females) and no more than 14 drinks/week (males) throughout participation - If a female of childbearing potential, agrees to use of contraception (licensed hormonal method, intrauterine device, condoms with contraceptive foam, abstinence, or partner vasectomy) throughout participation - Able to understand and comply with study procedures and provide written informed consent Exclusion: - History of congestive heart failure or certain cardiac conditions including coronary artery disease, uncontrolled hypertension, or hypotension - Bronchial asthma, nonallergic bronchospasm, renal failure or dialysis, diabetes mellitus, hyperthyroidism, fibromyalgia, or uncontrolled seizures - Currently taking a β-blocker or certain other medications including haloperidol, intravenous verapamil, or reserpine - Currently taking an opioid medication - Daily prescription medication, occlusal splint therapy, or an investigational drug or treatment for pain management within past 30 days - Injection therapy or certain other pain management techniques within last 2 weeks - Facial trauma or orofacial surgery within past 6 weeks - Active orthodontic treatment - History of major depression or other psychiatric disorder requiring hospitalization within past 6 months - Treatment for drug or alcohol abuse within the last year - Smokes 25 or more cigarettes/day - Currently receiving chemotherapy or radiation therapy - Pregnant or breastfeeding Inclusion: - Diagnostic criteria for TMD: Group II, Masticatory Muscle Disorders, Myalgia - Facial pain for at least 3 months (and at least 10 of the last 30 days at Visit 0) - Average pain intensity rating ≥30 (0-100 numeric rating scale) over the past week or average daily pain intensity rating ≥30 on the same scale on at least 3 days over the past week - Agrees to terms for continuing/discontinuing certain prescription/over-the-counter pain medications throughout participation - Agrees to not commence new prescription medication, injection therapy, occlusal splint therapy or certain other pain management techniques throughout participation - Agrees to limit consumption of alcohol to no more than 7 drinks/week (females) and no more than 14 drinks/week (males) throughout participation - If a female of childbearing potential, agrees to use of contraception (licensed hormonal method, intrauterine device, condoms with contraceptive foam, abstinence, or partner vasectomy) throughout participation - Able to understand and comply with study procedures and provide written informed consent Exclusion: - History of congestive heart failure or certain cardiac conditions including coronary artery disease, uncontrolled hypertension, or hypotension - Bronchial asthma, nonallergic bronchospasm, renal failure or dialysis, diabetes mellitus, hyperthyroidism, fibromyalgia, or uncontrolled seizures - Currently taking a β-blocker or certain other medications including haloperidol, intravenous verapamil, or reserpine - Currently taking an opioid medication - Daily prescription medication, occlusal splint therapy, or an investigational drug or treatment for pain management within past 30 days - Injection therapy or certain other pain management techniques within last 2 weeks - Facial trauma or orofacial surgery within past 6 weeks - Active orthodontic treatment - History of major depression or other psychiatric disorder requiring hospitalization within past 6 months - Treatment for drug or alcohol abuse within the last year - Smokes 25 or more cigarettes/day - Currently receiving chemotherapy or radiation therapy - Pregnant or breastfeeding Temporomandibular Disorders Temporomandibular Joint Disorders Temporomandibular Joint Dysfunction Syndrome "Temporomandibular disorder" (TMD) encompasses all musculoskeletal disorders of the masticatory system and includes myalgia, arthralgia, temporomandibular joint (TMJ) disc displacements, and TMJ degenerative joint diseases.

Primary Outcomes

Description: Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary and divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome.

Measure: Change in the Weekly Mean Pain Index After 9 Weeks of Treatment