SNPMiner Trials by Shray Alag


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Report for SNP rs25531

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 5 clinical trials

Clinical Trials


1 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

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 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)

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 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

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 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

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 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)

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: ] 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"

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: 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)

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: 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

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: 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

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: 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

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: 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

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: 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).

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 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

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 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

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: 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

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: 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)

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: 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

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: 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

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: 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"

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: 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"

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: 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"

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: 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"

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: 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"

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: 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"

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: 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.

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: 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

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: 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

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: 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

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: 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)

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: 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.

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); Pre/Post TSST

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"

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)

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)".

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: 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".

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: 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)".

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: 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)".

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: 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).

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: 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)".

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: 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)".

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: 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)".

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: 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)".

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: 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)".

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: 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)".

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 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)".

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: 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)".

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 range of experience emotions, and differentiation of experienced emotions.

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

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: 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.

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: 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)".

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 compassionate and self-image goals.

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

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: 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".

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: 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 )".

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: 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".

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: 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.

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: 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)".

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: 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".

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: 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)".

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

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

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: 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)".

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: 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)".

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: 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)".

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: 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)".

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

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

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: 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)".

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: 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)".

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: 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)".

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: 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)".

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

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

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: 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)".

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 lonliness.

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

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: 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)".

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: 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)"

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: 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)".

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 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

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 degrees to which respondent agrees with partner, do activities together, or satisfaction with partner.

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

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 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)"

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 the feelings of closeness to others

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

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: 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"

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: 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"

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: 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)"

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: 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)"

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: 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)"

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: 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)"

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: 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)".

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)

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.

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. It was used of matching participants into cohorts.

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.

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. It was used of matching participants into cohorts.

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

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

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

2 Improving Learning and School Functioning in Latino Children With Cancer

This randomized clinical trial studies how well a high-intensity intervention parenting program works in improving learning and school functioning in Latino children with acute leukemia or lymphoblastic lymphoma. A high-intensity intervention program may help doctors to see whether training parents or caregivers in specific parenting skills and "pro-learning" behaviors will result in better learning and school outcomes for Latino children with acute leukemia or lymphoblastic lymphoma. It is not yet known if a high-intensity intervention program is more beneficial than a standard of care lower intensity parenting intervention.

NCT03178617 Caregiver Childhood Acute Lymphoblastic Leukemia Childhood Acute Myeloid Leukemia Childhood Lymphoblastic Lymphoma Acute Leukemia Parent Other: Educational Intervention Other: Educational Intervention Other: Quality-of-Life Assessment Other: Questionnaire Administration
MeSH: Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Lymphoma, Non-Hodgkin
HPO: Leukemia Lymphoma Non-Hodgkin lymphoma

SECONDARY OBJECTIVES: I. Explore the associations between neurocognitive performance and polymorphisms in candidate genes previously reported to explain cognitive variability in childhood cancer survivors (e.g., the catechol-O-methyltransferase Val158Met polymorphism and the nitric oxide synthase [NOS3] 894T allele) or involved in the stress response (e.g., the Serotonin transporter rs25531 and the Glucocorticoid receptor rs6190).

Primary Outcomes

Description: Measured by the parent-reported Pediatric Quality of Life Inventory school domain.

Measure: Change in child's health-related quality of life school functioning

Time: Baseline up to 12 months

Description: Measured by the Efficacy scale from the Parent Knowledge, Beliefs and Behaviors Questionnaire-3rd Revision (PBQ-R3).

Measure: Change in parental efficacy

Time: Baseline up to 12 months

Measure: Children's neurocognitive functioning as measured by performance scores on Conner's Computerized Test

Time: Up to 12 months

Secondary Outcomes

Description: Measured by WIAT: reading and math scores and classroom grades from school report cards.

Measure: Objective academic performance (Child)

Time: Up to 12 months

Description: Measured by the Conners Parent Report Attention subscale.

Measure: Attention performance (Child)

Time: Up to 12 months

Description: Measured by PBQ-R3 Behaviors Scale.

Measure: Frequency of pro-learning behaviors (Parent)

Time: Up to 12 months

Description: Measured by the Parents' weekly time spent with child in pro-learning behaviors and activities.

Measure: Frequency of pro-learning behaviors (Parent)

Time: Up to 12 months

Description: Measured by PBQ-R3 Knowledge scale.

Measure: Knowledge of pro-learning parenting (Parent)

Time: Up to 12 months

Measure: Children's scores on other neurocognitive tests as assessed by learning, memory, and processing speed

Time: Up to 12 months

Measure: Parental reports of their children's HRQOL as measured by the PedsQL parent proxy questionnaire

Time: Up to 12 months

3 Efficacy of Transcranial Direct Current Stimulation for Severe Refractory Primary Dysmenorrhea: Translational and Genetic Neuroimaging Studies

Primary Dysmenorrhea (PDM), defined as menstrual pain without discernable organic causes, is inexorably common in adolescent women, about 40-90% of women may suffer from it, and 20% of them can be severe in the context of being refractory to medication, daily function impairment, and having pain of severe degree. Novel therapeutic method is in need for pain alleviation for this particular phenotype. We have previously reported that PDM females may engage motor-cortex based descending pain modulation system in our resting-state functional Magnetic Resonance Imaging (rs-fMRI) and thermal pain-activation fMRI studies. Based on the reported analgesic efficacy of transcranial Direct Current Stimulation (tDCS) on the motor cortex for various experimental painful conditions and clinical pain disorders, we reason that tDCS can be effective for the severe and medication-refractory PDM patients. This study aim to investigate the analgesic efficacy of tDCS in severe PDMs and to elucidate the dynamic brain neuroplasticity in the context of functional connectivity (FC) of pain matrix after tDCS intervention. We will recruit 30 severe PDMs and randomly allocate them to either real or sham group in a triple-blind manner. rs-fMRI for functional connectivity analysis will be performed before and after the tDCS intervention. The imaging data will be correlated with behavioral and psychological measurements. This is the first study in the literature investigating the tDCS efficacy for severe PDM. The result can promise a new possibility for clinical application.

NCT03594916 Primary Dysmenorrhea Device: Active tDCS Device: Sham tDCS
MeSH: Dysmenorrhea
HPO: Dysmenorrhea

To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen.

Primary Outcomes

Description: pain scale; from 0 to 10; score 0: no pain, score 10: unbearable pain

Measure: Visual Analog Scale (VAS)

Time: change from baseline (1st menstrual phase, before tDCS) at one month (2nd menstrual phase, with tDCS), change from baseline (1st menstrual phase, before tDCS) at two months (3rd menstrual phase)

Description: Resting-state functional magnetic resonance imaging (rs-fMRI) is a well established method of functional magnetic resonance imaging (fMRI) that is used to evaluate regional interactions in the brain that occur in a resting (task-negative) state, when a subject is not performing an explicit task. Functional connectivity is the connectivity between brain regions that share functional properties, it can be defined as the correlation between spatially remote neurophysiological events, expressed as the neural networks of brain.

Measure: Functional connectivity of rs-fMRI Imaging

Time: change from baseline (before tDCS, before 2nd menstrual phase) at one week (after tDCS completion), change from baseline (before tDCS, before 2nd menstrual phase) at four weeks (before the 3rd menstrual phase)

Secondary Outcomes

Description: To assess the threshold of thermal sensation (cold, cold-pain, heat, heat-pain; from 0 to 50 centigrade temperature), according to the established protocol of an ascending limit approach for heat pain and a descending limit approach for cold pain.

Measure: Quantitative sensory testing (QST)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 20 to 80; score 20: not anxious, score 80: extremely anxious

Measure: Spielberger State-Trait Anxiety Inventory (STAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 0 to 63; score 0: not anxious, score 63: extremely anxious

Measure: Beck Anxiety Inventory (BAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess depressive symptoms; from 0 to 63; score 0: not depressed, score 63: extremely depressed

Measure: Beck Depression Inventory (BDI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain-maladaptive psychological status; from 0 to 52; score 0: not pain Catastrophizing , score 52: extremely pain Catastrophizing

Measure: Pain Catastrophizing Scale (PCS)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain status; from 0 to 78; score 0: not painful, score 78: extremely painful

Measure: Long-form McGill Pain Questionnaire (MPQ)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess quality of life; he SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. From 0 to 100; score 0: equivalent to maximum disability, score 100: no disability.

Measure: Short-Form Health Survey (SF-36)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess testosterone, progesterone, estrogen

Measure: Blood Hormones Measurement

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase)

Description: To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen

Measure: Genotyping

Time: baseline

Description: To assure blinding efficacy; Patients do self-assessment about whether they receive real tDCS or sham tDCS. Assessment questionnaire:1 or 0. 1: real tDCS; 0: sham tDCS.

Measure: Efficacy of tDCS blinding

Time: At 1 months after tDCS intervention

4 Neuromodulation Effect of Transcranial Direct Current Stimulation in Severe Refractory Primary Dysmenorrhea: BDNF and MEG Study

Primary Dysmenorrhea (PDM), defined as menstrual pain without discernable organic causes, is inexorably common in adolescent women, about 40-90% of women may suffer from it, and 20% of them can be severe in the context of being refractory to medication, daily function impairment, and having pain of severe degree. Novel therapeutic method is in need for pain alleviation for this particular phenotype. It has been reported that PDM females may engage motor-cortex based descending pain modulation system in our resting-state functional Magnetic Resonance Imaging (rs-fMRI) and thermal pain-activation fMRI studies. Based on the reported analgesic efficacy of transcranial Direct Current Stimulation (tDCS) on the motor cortex for various experimental painful conditions and clinical pain disorders, it is plausible that tDCS can be effective for the severe and medication-refractory PDM patients. This study aim to investigate the analgesic efficacy of tDCS in severe PDMs and to elucidate the dynamic brain neuroplasticity in the context of experimental pain after tDCS intervention. Thirty severe PDMs will be recruited and randomly allocated to either real or sham group in a triple-blind manner. Experimental pain electrical stimulation will be performed before and after the tDCS intervention. The experimental pain-evoked magnetoencephamographic (MEG) data will be correlated with behavioral and psychological measurements. This is the first study in the literature investigating the tDCS efficacy for acute pain in severe PDM. The result can promise a new possibility for clinical application.

NCT03608215 Primary Dysmenorrhea Device: Active tDCS Device: Sham tDCS
MeSH: Dysmenorrhea
HPO: Dysmenorrhea

To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen.

Primary Outcomes

Description: pain scale; from 0 to 10; score 0: no pain, score 10: unbearable pain

Measure: Visual Analog Scale (VAS)

Time: change from baseline (1st menstrual phase, before tDCS) at one month (2nd menstrual phase, with tDCS), change from baseline (1st menstrual phase, before tDCS) at two months (3rd menstrual phase)

Description: Somatosensory evoked magnetic fields (SEFs) is a well established magnetoencephalographic (MEG) cortical response evoked by electric stimulation. SEFs to experimental pain stimulation using electrical stimulator applied on the skin over the trajectory of median nerve will be used to evaluate pain-evoked cortical response.

Measure: Somatosensory evoked magnetic fields to experimental pain

Time: change from baseline (before tDCS, before 2nd menstrual phase) at one week (after tDCS completion), change from baseline (before tDCS, before 2nd menstrual phase) at four weeks (before the 3rd menstrual phase)

Secondary Outcomes

Description: To assess the threshold of thermal sensation (cold, cold-pain, heat, heat-pain; from 0 to 50 centigrade temperature), according to the established protocol of an ascending limit approach for heat pain and a descending limit approach for cold pain.

Measure: Quantitative sensory testing (QST)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 20 to 80; score 20: not anxious, score 80: extremely anxious

Measure: Spielberger State-Trait Anxiety Inventory (STAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 0 to 63; score 0: not anxious, score 63: extremely anxious

Measure: Beck Anxiety Inventory (BAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess depressive symptoms; from 0 to 63; score 0: not depressed, score 63: extremely depressed

Measure: Beck Depression Inventory (BDI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain-maladaptive psychological status; from 0 to 52; score 0: not pain Catastrophizing , score 52: extremely pain Catastrophizing

Measure: Pain Catastrophizing Scale (PCS)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain status; from 0 to 78; score 0: not painful, score 78: extremely painful

Measure: Long-form McGill Pain Questionnaire (MPQ)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess quality of life; he SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. From 0 to 100; score 0: equivalent to maximum disability, score 100: no disability.

Measure: Short-Form Health Survey (SF-36)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess testosterone, progesterone, estrogen

Measure: Blood Hormones Measurement

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase)

Description: To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen

Measure: Genotyping

Time: baseline

Description: To assure blinding efficacy; Patients do self-assessment about whether they receive real tDCS or sham tDCS. Assessment questionnaire:1 or 0. 1: real tDCS; 0: sham tDCS.

Measure: Efficacy of tDCS blinding

Time: At 1 months after tDCS intervention

5 The Role of Sex Steroids and Serotonin Brain Dynamics in Perinatal Mental Health

Hormonal transitions such as across pregnancy and postpartum may trigger depressive episodes in some women. It is not known why, but estrogen sensitivity may play a critical role. A preclinical human risk model showed that depressive symptoms induced by pharmacological sex-hormone manipulation is linked to increases in serotonin transporter (SERT) brain binding, which lowers serotonergic brain tone. It is currently unknown if these findings translates to women across pre- to postpartum transitions. This longitudinal project studies a group of women who will deliver by planned caesarian, thus permitting the collection of cerebrospinal fluid (csf) containing central markers of serotonergic signaling, at the latest point in pregnancy. The women are followed across late pregnancy, delivery and 6 months postpartum to illuminate relations between sex-hormones, stress-regulation, estradiol sensitivity, csf markers of neurotransmission, serotonin transporter genotype variance, and potential development of subclinical or manifest depressive symptoms. Further, markers of relevance for the infant brain development and stress-regulation will be obtained from placenta tissue and umbilical cord blood. A subgroup of 70 women will participate in a brain imaging program early postpartum (week 3-5), which includes an evaluation of brain activity and structure and in vivo molecular brain imaging serotonergic markers. Thus, serotonergic markers in csf can be combined with postpartum molecular brain imaging of key features of serotonin signaling. Women in the imaging program are selected based on variation in their level of mental distress immediately postpartum (day 2-5). The study's main hypothesis is that women with high-expressing SERT genotypes are more sensitive to peripartum hormonal transition in terms of changes in serotonergic tone and emergence of depressive symptoms and that such an association will be stronger in the presence of candidate gene transcript biomarkers of oestrogen sensitivity. A further hypothesis is that in vivo molecular brain imaging and csf based serotonergic markers will be associated with depressive symptoms both early and later postpartum. Ideally, this project will provide a rationale for future targeted prevention and/or treatment of perinatal depression in women at high risk, which holds grand potential to protect not only mother but also infant brain health long-term.

NCT03795688 Major Depressive Disorder Perinatal Depression Other: Pregnancy
MeSH: Depressive Disorder Depressive Disorder, Major
HPO: Depressivity

L or S variants, and further subtyping on rs25531 haplotype L(A)L(A) vs LGLA, LGLG or variants containing as S as specified above..

Primary Outcomes

Description: Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Total group

Measure: Depressive symptoms

Time: Week 3-6 postpartum

Description: Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

Measure: Depressive symptoms

Time: Week 3-6 postpartum

Description: 116 a priori defined gene transcripts, which where differentially expressed in third trimester of women who later developed perinatal depression with postpartum onset relative to pregnant women who did not and to other depressed (reference Mehta et al, 2014, Psychological Medicine) and confirmed to be coupled to estrogen fluctuations (Mehtaet al. 2018 British Journal of Psychiatry) will be evaluated in the total group. Also DNA methylation of the genes of these transcripts will be determined and analysed in terms of their predictive value (above chance) for perinatal depression.

Measure: Gene transcript and DNA methylation markers of estrogen sensitivity

Time: Prior to caesarean section

Description: Latent variable construct of brain 5-HT4R level based on quantification of 5-HT4R binding from 11C-SB207145 positron emission tomography in primary volumes of interest; neocortex, nucleus caudatus, putamen and hippocampus. Assessed in imaging group.

Measure: Cerebral serotonin 4 receptor binding postpartum

Time: Week 3-6 postpartum

Description: Assessed in total group

Measure: CSF levels of GABA

Time: On day of caesarean section

Description: Assessed in total group

Measure: CSF levels of serotonin metabolite (5-HIAA)

Time: On day of caesarean section

Description: Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

Measure: Cortisol awakening response

Time: Week 3-6 postpartum

Description: Provides an estimate of cortisol exposure up to 6 months prior to delivery, total group

Measure: Hair cortisol level mothers

Time: On day of caesarean section.

Description: Provides an estimate of fetal cortisol exposure, infants from total group

Measure: Hair cortisol level newborns

Time: Day 0-5 postpartum.

Description: Hippocampal brain volume (including hippocampus) from structural MRI, imaging group.

Measure: Hippocampal volumes

Time: Week 3-6 postpartum.

Description: fMRI (BOLD response) based assessment of brain activity in response to reward, relative to non-reward, stimuli. Assessed in imaging cohort

Measure: functional MRI response to reward

Time: Week 3-6 postpartum.

Description: rsfMRI based spontaneous co-fluctuations in low frequency BOLD signal, (functional connectivity). Assessed with rsfMRI scan in the resting state, i.e. non-goal oriented spontaneous thought and awake. Assessed in imaging group.

Measure: Resting state functional connectivity MRI

Time: Week 3-6 postpartum

Description: Change in epigenetic SERT status from late pregnancy to postpartum week 3-6.

Measure: Change in epigenetic SERT status

Time: From just before delivery to 3-6 weeks postpartum

Description: Composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

Measure: Concentration of inflammatory markers, i.e hsCRP and immunoactive cytokines, in peripheral blood

Time: At week 3-6

Description: fMRI (BOLD response) based assessment of brain activity to emotionally salient, relative to neutral, stimuli. Assessed in imaging cohort.

Measure: functional MRI response to emotional faces

Time: Week 3-6 postpartum.

Secondary Outcomes

Description: Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

Measure: Depressive symptoms

Time: Day 3-5 postpartum

Description: Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

Measure: Depressive symptoms

Time: Week 12 postpartum

Description: Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Assessed in total group

Measure: Depressive symptoms

Time: Day 3-5 postpartum

Description: Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Assessed in all

Measure: Depressive symptoms

Time: 6 months postpartum

Description: Assessed in total group

Measure: CSF levels of serotonin

Time: On day of caesarean section

Description: Assessed in total group

Measure: CSF levels of dopamine metabolites

Time: On day of caesarean section

Description: Assessed in total group

Measure: CSF levels of noradrenaline metabolites

Time: On day of caesarean section

Description: Composite measure of IFN-c, IFN-alfa TNF-alfa og IL-6, in total group

Measure: CSF levels of inflammatory markers

Time: On day of caesarean section

Description: Estradiol level in peripheral blood, total group

Measure: Estradiol level

Time: Prior to caesarean section.

Description: Estradiol level peripheral blood, total group

Measure: Estradiol level

Time: At week 3-6 postpartum.

Description: Estradiol change pre- to postpartum, peripheral blood total group

Measure: Change in estradiol level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Progesterone level in peripheral blood

Measure: Progesterone level

Time: Prior to caesarean section.

Description: Progesterone level in peripheral blood

Measure: Progesterone level

Time: At week 3-6 postpartum.

Description: Progesterone change pre- to postpartum, peripheral blood total group

Measure: Change in progesterone level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Allopregnanolone level in peripheral blood

Measure: Allopregnanolone level

Time: Prior to caesarean section.

Description: Allopregnanolone level in peripheral blood

Measure: Allopregnanolone level

Time: At week 3-6 postpartum.

Description: Change in allopregnanolone level in peripheral blood

Measure: Change in allopregnanolone level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Cortisol change pre- to postpartum, peripheral blood total group

Measure: Change in cortisol level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

Measure: Cortisol awakening response

Time: Week 12 postpartum

Description: Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

Measure: Cortisol awakening response

Time: Prior to caesarean section

Description: Change in cortisol awakening response, from caesarean section to 3-6 weeks postpartum.

Measure: Change in cortisol awakening response

Time: ´From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the SERT gene, total group

Measure: DNA methylation of the SERT gene

Time: Prior to caesarean section

Description: DNA Methylation status for the SERT gene, total group

Measure: DNA methylation of the SERT gene

Time: Week 3-6 postpartum

Description: Methylation status for the FK506-binding protein 51 (FKBP5) gene, total group

Measure: DNA methylation of the FK506-binding protein 51 (FKBP5) gene

Time: Prior to caesarean section.

Description: Methylation status for the FK506-binding protein 51 (FKBP5) gene, total group

Measure: DNA methylation of the FK506-binding protein 51 (FKBP5) gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the FK506-binding protein 51 (FKBP5) gene from late pregnancy to postpartum week 3-6.

Measure: Change in DNA methylation of the FK506-binding protein 51 (FKBP5) gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the glucocorticoid receptor gene, total group

Measure: DNA methylation of the glucocorticoid receptor gene

Time: Prior to caesarean section.

Description: Methylation status for the glucocorticoid receptor gene, total group

Measure: DNA methylation of the glucocorticoid receptor gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the glucocorticoid receptor gene from late pregnancy to postpartum week 3-6.

Measure: Change in DNA methylation of the glucocorticoid receptor gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the COMT gene, total group

Measure: DNA methylation of the COMT gene

Time: Prior to caesarean section.

Description: Methylation status for the COMT gene, total group

Measure: DNA methylation of the COMT gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the COMT gene from just before delivery to 3-6 weeks postpartum

Measure: Change in DNA methylation of the COMT gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the MAO-A gene, total group

Measure: DNA methylation of the MAO-A gene

Time: Prior to caesarean section.

Description: Change in methylation status for the MAO-A gene, total group

Measure: Change in DNA methylation of the MAO-A gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the MAO-A gene, total group

Measure: DNA methylation of the MAO-A gene

Time: Week 3-6 postpartum

Description: Methylation status for the oxytocin receptor gene, total group

Measure: DNA methylation of the oxytocin receptor gene

Time: Prior to caesarean section.

Description: Methylation status for the oxytocin receptor gene, total group

Measure: DNA methylation of the oxytocin receptor gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the oxytocin receptor gene, total group

Measure: Change in DNA methylation of the oxytocin receptor gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the oxytocin gene, total group

Measure: DNA methylation of the oxytocin gene

Time: Prior to caesarean section.

Description: Methylation status for the oxytocin gene, total group

Measure: DNA methylation of the oxytocin gene

Time: Week 3-6 postpartum

Description: Change methylation status for the oxytocin gene, total group

Measure: Change in DNA methylation of the oxytocin gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

Measure: Systemic inflammation peripheral blood hsCRP and immunoactive cytokines

Time: Prior to caesarean section.

Description: Change in composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

Measure: Change in systemic inflammation peripheral blood hsCRP and immunoactive cytokines

Time: From baseline (caesarean section to week 3-6 postpartum

Description: Family History Assessment Module (OS-FHAM). Number of first degree relatives with a history of depressive episodes or bipolar disorder. Total group.

Measure: Self reported family history of mood disorders

Time: Day 3-5 postpartum or before

Description: Barratt Impulsiveness Scale (BIS-11), self-reported. Range: 30-120. Total group.

Measure: Self reported impulsiveness score

Time: Day 3-5 postpartum or before

Description: NEO-PI-R - Revised NEO Personality Inventory, self-reported. Participants may score 20-80 for each of the personality traits: openness, conscientiousness, extraversion, agreeableness, and neuroticism. The higher the score, the more prominent is the personality trait. Total group.

Measure: Self reported Neuroticism score from NEO personality questionnaire

Time: Day 3-5 postpartum or before

Description: Parental bonding instrument (PBI), both parents, self-reported. Total group.

Measure: Self reported parental bonding quality

Time: Day 3-5 postpartum or before

Description: Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

Measure: Self-reported perceived stress

Time: Day 3-5 postpartum

Description: Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

Measure: Self-reported perceived stress

Time: Week 3-6 postpartum

Description: Change in Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

Measure: Change in self-reported perceived stress

Time: Change from day 3-5 to week 3-6 postpartum

Description: Snaith-Hamilton Pleasure Scale (SHAPS), range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

Measure: Self-reported anhedonia

Time: Day 3-5 postpartum

Description: Snaith-Hamilton Pleasure Scale (SHAPS), range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

Measure: Self-reported anhedonia

Time: Week 3-6 postpartum

Description: Change in Snaith-Hamilton Pleasure Scale (SHAPS) score, range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

Measure: Change in self-reported anhedonia

Time: Change from day 3-5 to week 3-6 postpartum

Description: Rumination Response Scale (RRS), range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

Measure: Self-reported rumination

Time: Day 3-5 postpartum

Description: Rumination Response Scale (RRS), range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

Measure: Self-reported rumination

Time: Week 3-6 postpartum

Description: Change in Rumination Response Scale (RRS) score, range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

Measure: Change in elf-reported rumination

Time: Change from day 3-5 to week 3-6 postpartum

Description: Profile of Mood States (POMS), range 0-260, a score of 0 indicates no mood disturbance. Total group.

Measure: Self-reported mood

Time: Day 3-5 postpartum

Description: Profile of Mood States (POMS), range 0-260, a score of 0 indicates no mood disturbance. Total group.

Measure: Self-reported mood

Time: Week 3-6 postpartum

Description: Change in Profile of Mood States (POMS) score, range 0-260, a score of 0 indicates no mood disturbance. Total group.

Measure: Change in self-reported mood

Time: Change from day 3-5 to week 3-6 postpartum

Description: Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

Measure: Self-reported sleep quality

Time: Day 3-5 postpartum

Description: Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

Measure: Self-reported sleep quality

Time: Week 3-6 postpartum

Description: Change in Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

Measure: Change in self-reported sleep quality

Time: Change from day 3-5 to week 3-6 postpartum

Description: Brief symptom Inventory-53 item (BSI-53), range 0-212, increasing score means worsening of symptoms.Total group.

Measure: Self-reported psychiatric symptoms

Time: Day 3-5 postpartum

Description: Brief symptom Inventory-53 item (BSI-53), range 0-212, increasing score means worsening of symptoms.Total group.

Measure: Self-reported psychiatric symptoms

Time: Week 3-6 postpartum

Description: Change in Brief symptom Inventory-53 item (BSI-53) score, range 0-212, increasing score means worsening of symptoms.Total group.

Measure: Change in self-reported psychiatric symptoms

Time: Change from day 3-5 to week 3-6 postpartum

Description: WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

Measure: Self-reported well-being

Time: Day 3-5 postpartum

Description: WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

Measure: Self-reported well-being

Time: Week 3-6 postpartum

Description: Change in WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

Measure: Change in self-reported well-being

Time: Change from day 3-5 to week 3-6 postpartum

Description: State Trait Anxiety Inventory (STAI-AD-D), state and trait subscales each have a range of 20-80, 20 means no anxiety. Total group.

Measure: Self-reported anxiety

Time: Day 3-5 postpartum

Description: State Trait Anxiety Inventory (STAI-AD-D), state subscale range 20-80, 20 means no anxiety. Total group.

Measure: Self-reported anxiety

Time: Week 3-6 postpartum

Description: Change in State Trait Anxiety Inventory (STAI-AD-D) score, state subscale range 20-80, 20 means no anxiety. Total group.

Measure: Change in self-reported anxiety

Time: Change from day 3-5 to week 3-6 postpartum

Description: Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

Measure: Self-reported obsessive and compulsive symptoms

Time: Day 3-5

Description: Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

Measure: Self-reported obsessive and compulsive symptoms

Time: Week 3-6 postpartum

Description: Change in Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

Measure: Change in self-reported obsessive and compulsive symptoms

Time: Change from day 3-5 to week 3-6 postpartum

Description: Performance on Simple Reaction Time, in imaging cohort.

Measure: Performance on Simple Reaction Time

Time: Week 3-6 postpartum

Description: Gray matter brain volume prefrontal cortex and anterior cingulate cortex

Measure: Gray matter brain volume prefrontal cortex and anterior cingulate cortex

Time: At week 3-6 postpartum

Description: Composite measure of serotonin, tryptophan og tryptofan hydroxylase levels relative to 5-HIAA, in placenta sample. Infants from total group

Measure: Serotonergic turnover in placenta

Time: At delivery.

Description: 11-beta-hydroxysteroid dehydrogenase type 2 activity in placenta. Infants from total group

Measure: 11-beta-hydroxysteroid dehydrogenase type 2 activity in placenta

Time: At delivery

Description: Composite measure of methylation status for the FKBP5, glucocorticoid receptor, 11-beta hydroxysteroid dehydrogenase type 2 genes. Infants from total group

Measure: Methylation status of genes relevant for stress-hormone regulation in placenta

Time: At delivery

Description: Composite measure of the methylation status for monoamine oxidase, serotonin receptor and serotonin transporter genes. Infants from total group

Measure: Methylation status of genes related to serotonergic signaling in placenta

Time: At delivery

Description: Composite measure of methylation status and gene transcript profiles of Glucocorticoid receptor, FKBP5, oxytocin and oxytocin receptors, Brain-derived neurotrophic factor (BDNF) genes. Assessed in blood from umbilical cord blood sample from infants, total group.

Measure: Methylation status and gene transcript profiles of relevance for early brain development and stress regulation in newborn infants

Time: At delivery.

Other Outcomes

Description: val158met (rs4680) status, binary variable, i.e. "val/val, val/met" vs "met/met" variants

Measure: COMT-genotype (rs4680) variant, i.e met/met vs other polymorphisms

Time: Prior to caesarean section.

Description: BDNF val66met (rs6265) status, binary variable, i.e. "val/val" versus "met-carrier" status

Measure: BDNF genotype (rs6265) status, i.e. val/val versus met-carrier variants

Time: Prior to caesarean section.

Description: 5-HTTLPR genotype status (binary), i.e. high-expressing LALA vs low-expressing (S or LG) variants, based on SLC6A4, i.e. L or S variants, and further subtyping on rs25531 haplotype L(A)L(A) vs LGLA, LGLG or variants containing as S as specified above.

Measure: 5-HTT genotype status, i.e LALA vs low-expressing (S or LG) variants

Time: Prior to caesarean section.

Description: In house interview based on Kennerley Maternity Blues Questionnaire, range: 0-28, higher score indicates more severe postpartum blues symptoms. High blues score is associated with greater risk for perinatal depression at week 3-6.

Measure: Postpartum blues symptoms

Time: Day 3-5 postpartum.

Description: In house interview based on Stein's Maternity Blues Scale, range 0-26. High blues score is associated with greater risk for perinatal depression at week 3-6.

Measure: Postpartum blues symptoms

Time: Day 3-5 postpartum.


HPO Nodes


Dysmenorrhea
Genes 16
PPARG LMNA FOS CYB5A CAVIN1 ANTXR1 INHBA CYP17A1 GPR101 PPARG CAV1 LMNA AGPAT2 CYP17A1 BSCL2 AIP
Leukemia
Genes 190
ATM KRAS KIT RPS15A NF1 MPL RPL35A RPL11 RPL18 DDX41 SBDS LPP ETV6 BUB1B F13A1 DNMT3A JAK2 NUP214 FANCD2 MSH6 FANCA PIGL NRAS TCIRG1 BUB1 TET2 FLT3 TAL1 ATRX TREX1 PDGFRA SRP54 RPS29 PTPN11 CALR FANCE WIPF1 SF3B1 GATA2 GLI1 STS SH3GL1 XRCC4 MPL SH2B3 EFL1 PIGA TREM2 CBL MPL RUNX1 MPL PIGL THPO FANCG NSD1 BRD4 NSUN2 SH2B3 RARA GATA2 NPM1 CBL CHIC2 ERBB3 GFI1 TERT KIT BCR ARHGAP26 DYNC2LI1 EVC SCN10A GATA1 ELANE RNASEH2B RPS14 SH2B3 JAK2 RPL15 SBDS NRAS RPL26 RPL27 ADA2 RPS7 TYROBP F13B MSH2 BCR WAS TERC TP53 TRIP13 MYD88 NUTM1 RPS24 GNB1 TP53 DNMT3A TERT NUMA1 NUP214 RPL5 SAMD9L TET2 CFTR POT1 FANCC RPS10 EP300 EVC2 BUB1B CEBPA BRCA2 DNAJC21 CALR SCN9A LIG4 ADAR BLM TET2 JAK2 SMPD1 RNASEH2C SCN11A GATA2 BUB3 PRSS1 KIF11 BCR RPL35 TAL2 SRP54 IFIH1 ABL1 PDGFRB KRAS RNASEH2A TET2 MLLT10 SRP54 DNAJC21 DKC1 RUNX1 APC LIG4 CBFB BLM THPO CALR NBN JAK2 MLH1 RPS19 ELANE SAMD9L RPL31 PMS2 ASXL1 TSR2 MLF1 PIK3CA DNAJC21 RUNX1 GFI1 SRSF2 SETBP1 HAX1 RPS26 RPS17 FLT3 RPS27 PIK3R1 KRAS CEP57 PICALM CREBBP GATA2 CTRC MYD88 TET2 RPS28 ABL1 RB1 SPINK1 GATA1 NBN JAK2 SAMHD1
Non-Hodgkin lymphoma
Genes 32
ATM FAS CASP10 CTLA4 FAS BCL10 CD28 BIRC3 FOXP1 TNFRSF1B MYC CCND1 ASXL1 ATM MALT1 CTLA4 CD28 SRSF2 KIT POLE IGH ADA TET2 FASLG PIK3R1 NTHL1 RASGRP1 TNFRSF1B PRKCD NBN RHOH IGH
Depressivity
Genes 377
AMACR BAZ1B PDCD1 PRKAR1A KCTD17 AFG3L2 DNAJC13 NSMF PRPH TBP DNA2 TOR1A UBQLN2 MED25 WFS1 TRNL1 ADH1C ND4 GNAS RFC2 FGF14 HMBS PLA2G6 SPAST PRKCG HTR2A SQSTM1 ATRX GABRA1 FGF8 FUS CLCN4 LMNB1 CLN6 TRNS2 GDAP2 PON2 GSN SNCA FAN1 XK TWNK PTS TRNQ RPS6KA3 TBX1 GLT8D1 OPTN PINK1 GTF2IRD1 NHLRC1 GBA TRNN PANK2 CRBN GNRH1 PSAP NDST1 GLUD2 SOD1 DNAJC6 LRRK2 DNMT1 PDE11A TAC3 DRD2 MAN1B1 HTT AP2S1 SPRY4 PGAP1 CBS SQSTM1 TOR1A AIMP1 TUSC3 PDGFB TWNK FMO3 SLC20A2 MECP2 CACNA1G CDH23 C9ORF72 FUS GPR35 TARDBP C9ORF72 HIRA IDUA HLA-DQB1 PRSS12 C9ORF72 CLIP2 PIGC HNMT JRK TRNF PAH CLRN1 ATXN2 CPOX CEP78 MSTO1 ELN CLCN4 CISD2 PROK2 PDGFB SGCE SLC6A4 KCNT1 PDGFRB UCHL1 MATR3 GABRG2 SMPD1 PRNP GNRHR KISS1R COQ2 HS6ST1 TNIK NEFH MAPT C9ORF72 ATP13A2 PARK7 NSUN2 SLC25A4 CCNF ANXA11 HLA-DQB1 TBL2 CPOX SNCAIP FIG4 TARDBP NOTCH3 LINS1 VAPB BMPR1A ARVCF SLC18A2 C19ORF12 MAPT ATXN10 POLG SLC45A1 KDM5B MST1 SEC24C B3GALNT2 MLH3 PPT1 FRRS1L JPH3 WDR11 PODXL ND6 ARMC5 HTRA2 AIP CRADD TTC19 MED23 ZC3H14 JMJD1C PRNP USH2A ATP1A3 TRNS1 ND5 EDC3 COASY UNC13A COMT UFD1 VCP POLG FMR1 PMS1 FMN2 PRNP PRNP CHD7 DCPS METTL23 DCTN1 TRNL2 GBA PPP2R2B ATP7B GTF2I USH1G PTPN22 SRPX2 TACR3 TWNK GNA11 TMEM106B SNCA CSF1R MLH1 TRNH PMS2 CLIP1 POLG2 ATXN8OS CASR VPS13C PON1 RSRC1 PPOX VCP HLA-DRB1 EZR DUSP6 BCS1L DCTN1 EHMT1 TRNL1 PRNP PDZD7 MSH6 MAPT EPHA4 POLG THOC2 CRKL CYP27A1 PLA2G6 ANG CC2D1A DCTN1 MYO7A CACNA1H HTT DNAJC5 COQ2 GRIN2A GP1BB DGUOK PRKN CHMP2B KRAS ARSA NR4A2 HNRNPA1 CHMP2B WASHC4 TRNS2 ATXN10 MSH2 CFAP410 PFN1 HMBS CACNA1G GNAS MYO7A SLC2A1 PINK1 POLG C9ORF72 PSEN1 ANOS1 PIK3CA ALMS1 TBC1D7 VCP TRNS1 PANK2 GBA TK2 LIMK1 CHCHD10 XPR1 PPARGC1A RPS20 USP8 ST3GAL3 ARMC5 HARS1 KCTD17 TAF15 AARS2 PER3 FGF14 CTSF TBP MECP2 MBOAT7 POLG PAH TREM2 USH1C TREM2 COX1 TBK1 C12ORF4 WARS2 STX16 ATXN8 SGCE ND1 ATXN8OS PRKACA TBK1 ARSG MAPK1 ATXN2 GRN ABCA7 OCRL KCNJ2 TRNW CHCHD10 COX3 RREB1 DAO GIGYF2 GPR101 TECR CDH23 ATP1A3 EPCAM ADGRV1 GNAS TCF4 GNAS GABRG2 PRNP KISS1 TGFBR2 SEMA4A TWNK GCH1 CIB2 COX2 FGFR1 PCDH15 WHRN LRRK2 TRAPPC9 RRM2B FMR1 RRM2B WFS1 FA2H FGF17 HBB PDGFRB SARS1 BCR EIF4G1 POLG ERBB4 GLA PER2 FBXO31 PON3 GLE1 PROKR2 VPS35 NEK1 MSTO1 LMAN2L GNAS DNMT1 GABRB3 CP TBX1 EPM2A PDGFRB GRIK2 SNCA VCP
Lymphoma
Genes 133
ATM KRAS CD19 IGH DDX41 BCL10 BIRC3 FOXP1 MS4A1 TP63 RAG1 LIG4 NFKB2 MSH6 TERC RECQL4 NTHL1 WIPF1 CTC1 LYST NOP10 RASGRP1 TNFRSF1B XRCC4 PRKCD NHP2 MAGT1 TNFRSF13B IGH RMRP RUNX1 CTLA4 DCLRE1C FAS ICOS RNF43 NSUN2 XIAP IL7R CASP10 BCL6 CDKN2A ATM IL2RG RTEL1 PARN NBN KIT TNFRSF13C TCF4 ICOS TNFSF12 CHEK2 USB1 CD19 CR2 NRAS MSH2 WAS BCL10 CASP10 MYD88 COL14A1 PRKCD TNFRSF13B MYC MDM2 SH2D1A CCND1 BCL10 CFTR CD27 PGM3 TCF4 CHD7 IGH LIG4 BLM BCL2 TET2 HLA-DRB1 PRSS1 NPM1 KIF11 ITK WRAP53 RAD54B TINF2 FAS DKC1 APC CD81 LIG4 BLM CD28 DKC1 AAGAB RAG2 TNFRSF1B MLH1 TNFRSF13C DNASE1L3 NFKB1 PMS2 ASXL1 IL2RG PRF1 PTEN MALT1 RAD54L CTLA4 CD28 PNP SRSF2 TNFSF12 STAT3 POLE ADA CR2 ADA FASLG PIK3R1 TP53 CTRC ZAP70 MYD88 RB1 RMRP SPINK1 TERT KLHDC8B NBN RHOH