Clinical trial NCT02797873: Emotional and Non-emotional Regulation in Patients With Emotional Instability and ADHD
Official title: Emotional and Non-emotional Regulation in Patients With Emotional Instability Personality Disorder (EIP) and Attention Deficit Hyperactivity Disorder (ADHD) Symptoms
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Emotional Instability Personality Disorder (Borderline Personality Disorder)
Attention Deficit Hyperactivity Disorder
Healthy Controls
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2016-06-14
Enrollment: 60
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to investigate how emotional and non-emotional regulation processes differ in EIP patients (with different levels of ADHD symptoms/ADHD-comorbidity) compared to controls. The investigators will test these participants' abilities to regulate emotional and non-emotional processes, reward anticipation and reward receipt while they undergo functional magnetic resonance imaging (fMRI). The participants' motor inhibition capacity on a behavioral level will also be investigated.

The hypothesis is that EIP patients will present with more deficits in emotion regulation processes compared to controls, even when controlling for ADHD symptoms. It is also hypothesized that higher levels of ADHD symptoms will correlate with dysfunctional non-emotional regulation processes, on a behavioral as well as brain mechanistic level.

Detailed description: Background: Comorbidity of Emotional Instability Personality Disorder (EIP) and Attention Deficit Hyperactivity Disorder (ADHD) is common, and the two patient groups partially exhibit similar problems. The main hypothesis is that the two disorders are mechanistically related. The investigators believe that the mechanisms underlying the problems are linked to two parallel regulating systems in the brain. Here, prefrontal and anterior cingulate systems are in focus. The first system - including the dorsolateral prefrontal cortex (dlPFC) and the caudal anterior cingulate cortex (cACC) - regulates non-emotional (and exteroceptive) information. The other system - including the lateral orbitofrontal prefrontal cortex (lObfc) and rostral anterior cingulate cortex (rACC) - regulates emotional (and interoceptive) information. The hypothesis is that the non-emotional/exteroceptive regulatory system is more affected in ADHD, while the emotional/interoceptive regulatory system is more affected in EIP.

Aims: The aim of this study is to differentiate between dysfunctional emotional regulation processes related to emotional instability symptoms (when controlling for non-emotional ADHD-like symptoms), and dysfunctional non-emotional regulation processes related to ADHD symptoms (when controlling for emotional instability symptoms).

Procedure:

* Participants: 30 young women from the Emotional Instability Unit at Child and Adolescent Psychiatry in Stockholm (Dialectic Behavioral Therapy unit ("DBT-teamet")), with traits of emotional instability and with varying levels of ADHD symptoms. 30 matched healthy controls.
* Tests:

Behavioral task: Stop Signal Task: measures participant's ability to inhibit a motor response. Outcome measures are Stop Signal Reaction Time (SSRT) and Go Reaction Time (GoRT)

fMRI task 1: Stroop task. Divided into 2 sessions of 10 minutes with 2 blocks in each. There are two types of blocks: Emotional Stroop task blocks (happy or fearful faces, with the word "HAPPY" or "FEAR" written across them) and Neutral Stroop task blocks (neutral faces of men and women with the word "MAN" or "WOMAN" written across them). Every other block is Emotional and every other is Neutral (balanced order between participants) so that each participant performs two emotional blocks and two neutral blocks. The task is to decide what emotion or gender is shown in the picture and ignore the word. Responses are made using a button box and reaction time is recorded for all the trials. Blood Oxygen Level Dependent (BOLD) signal is recorded in the brain during the task. Outcome measures are reaction times for the different trial types (incongruent(I) and congruent(C), also order dependent) as well as BOLD signal during these different types of trial.

fMRI task 2: Monetary Incentive Delay task (MID). Divided into 2 session of 10 minutes. Reward task in which the participant may win money (0 Swedish kronor (SEK), 10 SEK or 50 SEK in each trial). There is an anticipation phase in each trial, a response cue during which the participant needs to press a button as fast as she can, and an outcome phase in which feedback is presented of whether the participant has won the anticipated money or not. Outcome measures are BOLD activation during the anticipation phases of different levels of reward, and BOLD activation during the receipt/outcome phase of the different levels of reward. Reaction times for the different reward levels are also recorded.

The overall step-by-step procedure for each participant:

* Telephone screening (both participant and guardian): information about the study, MRI safety screening, check initial inclusion/exclusion criteria are met.
* Informed consent: sent by post to all legal guardians and the participant. Returned by post to test leader.
* The Strengths and Difficulties Questionnaire (SDQ) and socio-economic status questionnaires sent to one legal guardian and returned to test leader upon completion.
* Visit/Day 1: Assessment with questionnaires, interviews and behavioral testing (For selection of participants: Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV (SCID)-II interview Borderline and Antisocial parts, SDQ, Adult Self-Report Scale (ASRS), Autism Spectrum Quotient (AQ), Toronto Alexithymia Scale (TAS)-20, Ravens SPM, reading test, color vision test, questionnaire with additional questions. For characterization of participants: Brown-Attention Deficit Disorder (ADD), Mood and Feelings Questionnaire (MFQ), State and Trait Anxiety Inventory-Trait (STAI-T), Barratt's Impulsivity Scale (BIS)). Frankfurter Test und Training des Erkennens von fazialem Affekt (FEFA) 2 test (face recognition) and Stop signal test (SST). Approximately 3 hours.
* DAWBA computerized interview at home. Both participant and one legal guardian complete this.
* Additional information from patient records gathered, to verify current and previous diagnoses.
* Visit/Day 2: Assessments with questionnaires (STAI-S, last menstruation, sleepiness rating, motivation rating). MRI-scan: session 1: T1, Stroop session 1, Stroop session 2, T2. Break. Session 2: MID session 1, MID session 2. Break. Session 3: resting state, DTI. Assessments after scan: debriefing questionnaire, "After MID task" questionnaire. Approximately 3 hours.

Eligibility criteria: Inclusion Criteria:

* Undergone puberty
* Right-handed
* Monophasic contraceptives
* Speak Swedish fluently

Additional inclusion criteria EIP patients:

≥4/9 criteria of DSM-IV, measured by SCID-II interview

Exclusion Criteria:

* Impaired vision \> +/- 5 D or other vision problem (squinting or severe astigmatism)
* BMI \<17, BMI \>35 due to possible hormonal disturbance
* Some medical drugs: benzodiazepines, neuroleptics, mood stabilisers, central stimulants, other neuro pharmaceuticals. (SSRIs are ok)
* Not suitable for MRI scan (metal implants or severe claustrophobia)
* AQ-score \>26
* Alexithymia (≥52 in TAS20 questionnaire or poor score in facial recognition test (FEFA2));
* Mental retardation (IQ \<70 according to Ravens SPM)
* Reading difficulties (reading speed \>2 standard deviations slower than normal population of same age
* Established addiction problems (nicotine ok)
* Color blindness (\>10 points on Ishihara-test)
* Psychotic disorder (according to medical history, DAWBA, medical records)
* Anorexia nervosa that has required hospital care
* Bipolar disorder (according to DAWBA and medical records)
* Neurological disease (according to medical history and medical records)
* Endocrinological disease
* Other disease, condition or treatment that may substantially affect cognition

Primary outcomes:
measure: fMRI BOLD signal differences between groups - in Stroop task
timeFrame: Acquired during fMRI scan
measure: fMRI signal variations within patient group during Stroop task, depending on level of ADHD symptoms - in Stroop task
timeFrame: Acquired during fMRI scan
measure: Reaction times in Stroop task
timeFrame: Acquired during fMRI scan
measure: fMRI BOLD signal differences between groups - in Monetary Incentive Delay task (MID)
timeFrame: Acquired during fMRI scan
measure: fMRI BOLD signal differences within patient group during MID task, depending on level of ADHD symptoms - in MID task
timeFrame: Acquired during fMRI scan
measure: Reaction times in MID task
timeFrame: Acquired during fMRI scan
measure: Stop Signal reaction times (SSRT) from Stop Signal Task (SST)
timeFrame: Data necessary for estimation of SSRT acquired during fMRI scan
Secondary outcomes:
measure: Brown-ADD score
timeFrame: Acquired from questionnaire at first visit
measure: Mood and Feelings questionnaire
timeFrame: Acquired from questionnaire at first visit
measure: STAI-T score
timeFrame: Acquired from questionnaire at first visit
measure: Barratt's impulsivity scale (BIS)
timeFrame: Acquired from questionnaire at first visit
measure: STAI-S score
timeFrame: Baseline, acquired from questionnaire Day 2
measure: Sleepiness score
timeFrame: Acquired during MRI scan, on Day 2
measure: Motivation score
timeFrame: Acquired during MRI scan, on Day 2
measure: Structural MRI data - volume
timeFrame: Acquired during MRI scan
measure: Structural MRI data - surface area
timeFrame: Acquired during MRI scan
measure: Structural MRI data - thickness
timeFrame: Acquired during MRI scan
measure: Functional Connectivity (FC)
timeFrame: Acquired during resting state MRI scan
measure: Fractional Anisotropy (FA) of white matter
timeFrame: Acquired during Diffusion Tensor Imaging (DTI) scan
Other outcomes:
Locations:
Study officials:
References: