Please select the eligibility criteria that correspond to the clinical trial below.
Title: Psychological Treatments for Youth With Severe Irritability
Brief Summary: Background:

When children have severe irritability and temper outbursts, they can be so cranky or angry that it leads to problems at home, in school, and with friends. This is called Disruptive Mood Dysregulation Disorder (DMDD) and there have been no psychological treatments developed specifically for children with this problem. Researchers think two forms of therapy, Cognitive Behavioral Therapy (CBT) and Interpretation Bias Training (IBT), might help children with DMDD.

Objective:

To test two whether IBT and CBT can decrease severe irritability in children and youth.

Eligibility:

Children 8-17 years old with DMDD. Their symptoms must have started before age 10.

Design:

Participants will be screened with a review of their symptoms. Parents and participants will answer questions.

Participants can do only one or both of these treatments if they wish. Those who wish to do both will start with IBT.

Participants who do CBT will have 12-16 weekly meetings of research talk therapy. A parent will participate in part of the sessions.

Participants will talk about what makes them irritable and how it affects them. They may be put in situations that might make them annoyed or irritable.

Participants will rate how intense their irritability is. Parents and participants will complete rating scales, questionnaires, and interviews.

Participants will do practice activities at home.

Participants doing IBT will have up to 14 sessions over 10 weeks.

Participants will view 15 faces, one at a time, on a computer. They will choose if the face looks happy or angry on a computer. Sometimes the computer gives feedback. Participants will complete some sessions at the NIH and some at home.

Participants and parents answer questions about their progress.

...


Options:
A: Inclusion Criteria:

* Age: Parents 18 years or over; Child aged 30-59 months at identification;
* Child has moderate to severe intellectual disability (parent reported Adaptive Behaviour Assessment System (ABAS) General Adaptive Functioning 20-69);
* Written informed consent by parent/caregiver;
* Reports of challenging behaviour over a 6-month period but no less than 2 months.

Exclusion Criteria:

* Child has mild, profound or no LD on parent reported ABAS;
* Parent/carer has insufficient English language to complete study questionnaires;
* Another sibling is taking part in the study.
B: * INCLUSION AND EXCLUSION CRITERIA:

Inclusion and exclusion criteria for each group are outlined below. The total accrual ceiling is 2050, including subjects of both sexes, made up of the following 11 populations:

Pediatric patients with bipolar disorder or SMIBRD:

INCLUSION CRITERIA:

* Age 6-17
* Meet DSM criteria for BD
* Have a primary caregiver who can accompany him or her on trips to NIMH and provide reliable history and information.
* Have a psychiatrist who provides clinical care for their BSD.
* Be able to complete self-rating forms and to cooperate with other study procedures.

EXCLUSION CRITERIA:

* I.Q. \< 70
* Autistic disorder or more than mild autism spectrum disorder;
* Psychosis that interferes with the child s capacity to understand and comply with study procedures
* Unstable medical illness (e.g. severe asthma)
* Medical illness that could cause the symptoms of BSD (e.g. multiple sclerosis, thyroid disease)
* Pregnancy
* Substance abuse within two months of the initial evaluation, since alcohol and abused substances interfere with interpretation of fMRI and cognitive task data.
* NIMH IRP Employee family member

Adults with BD participating as individuals or as parents of at- risk children:

INCLUSION CRITERIA:

* DSM Bipolar Disorder
* Age 18-58
* Be able to complete self-rating forms and to cooperate with other study procedures.
* Medically safe to perform MRI

EXCLUSION CRITERIA:

* Diagnosis of schizophrenia or other current psychosis.
* Claustrophobia or anxiety that prevents participation in MRI
* Any serious medical illness, such as heart, liver, or kidney disease.
* A history of drug or alcohol abuse in the past 90 days.
* Current or past seizure disorder
* Currently unstable hyperthyroidism or hypothyroidism
* Currently receiving medical treatment that would affect mood, such as steroids
* Pregnant or breast-feeding.
* Active suicidal or homicidal thoughts or plans
* NIMH IRP Employee/family member

Healthy volunteer children and adolescents:

INCLUSION CRITERIA:

* Age- and sex- matched to the bipolar patients.
* Have an identified primary care physician.
* Speaks English

EXCLUSION CRITERIA

* I.Q. \< 70
* Any serious medical condition or condition that interferes with fMRI scanning
* Pregnancy
* Past or current diagnosis of any anxiety disorder (panic disorder, GAD, Separation Anxiety Disorder, Social Phobia), mood disorder (manic or hypomanic episode, major depression), OCD, PTSD, Conduct Disorder, psychosis, current suicidal ideation, Tourette
* Disorder, Autism Spectrum Disorder or ADHD.
* Substance abuse within two months prior to study participation or present substance abuse
* History of sexual abuse.
* Parent or sibling with Bipolar Disorder, recurrent MDD, or any disorder with psychosis.
* NIMH IRP Employee family member

Parents of healthy volunteer children (Amish and Non-Amish) and Healthy Adults (not parents):

INCLUSION CRITERIA:

* For healthy adults (not parents): Healthy adults age 25-58
* For parents of healthy volunteers: Parents of control subjects as outlined in B above
* Age 25-58
* Speaks English

EXCLUSION CRITERIA:

* IQ\< 70
* Any current psychiatric diagnosis
* NIMH IRP Employee/family member

Control subjects with ADHD but not BD:

INCLUSION CRITERIA:

* Age 8-17
* Currently meets DSM-IV criteria for ADHD
* t score \>65 on the Connors Parent scales
* Subjects with other psychiatric disorders including anxiety disorders, dysthymic disorder, past major depression, oppositional defiant disorder, tic disorders, and the learning, communication, and elimination disorders may be accepted

EXCLUSION CRITERIA

* IQ\<70
* Pregnancy
* Ongoing medical illness or neurological disorder other than ADHD
* Any condition that would interfere with the participants ability to perform fMRI or other research tasks
* Current Major Depression
* Any past or present manic or hypomanic episode.
* NIMH IRP Employee family member

First- and Second-degree relatives of patients with BD:

INCLUSION CRITERIA:

* First degree relatives (parent or sibling) or second-degree relative (grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling) of patients with BD
* Age 3-58

EXCLUSION CRITERIA:

* Active psychosis
* Dementia
* IQ \< 70
* Any clinical condition in need of immediate care
* Any chronic medical illness resulting in impaired CNS function
* Any condition that interferes with the participants ability to perform research tasks
* NIMH IRP Employee/family member

Amish Community children with BD:

INCLUSION CRITERIA:

* Age 8-17
* Meet DSM-IV criteria for BD
* Have a primary caregiver who can provide a reliable history
* Be able to complete self-rating forms and to cooperate with other study procedures.

EXCLUSION CRITERIA:

* IQ\<70
* Active psychosis
* Any clinical condition in need of immediate care
* Any chronic medical illness resulting in impaired CNS function
* Any condition that would interfere with the participants ability to perform behavioral research tasks
* Limitations with English that would interfere with understanding consent/assent, interview, or task instructions.
* NIMH IRP Employee family member

Amish Community Adults with BD:

INCLUSION CRITERIA:

* DSM-IV Bipolar Disorder
* Age 18-58
* Be able to complete self-rating forms and to cooperate with other study procedures.

EXCLUSION CRITERIA:

* Diagnosis of schizophrenia or other current psychosis.
* Any serious medical illness, such as heart, liver, or kidney disease.
* A history of drug or alcohol abuse in the past 90 days.
* Current or past seizure disorder
* Currently unstable hyperthyroidism or hypothyroidism
* Currently receiving medical treatment that would affect mood, such as steroids
* Active suicidal or homicidal thoughts or plans
* Limitations with English that would interfere with understanding consent/assent, interview, or task instructions.
* NIMH IRP Employee/family member

Amish Community at-risk subjects:

INCLUSION CRITERIA:

* Age 8-17
* Parent or sibling (first-degree relative) diagnosed with BD

EXCLUSION CRITERIA:

* IQ\<70
* Active psychosis
* Any clinical condition in need of immediate care
* Any chronic medical illness resulting in impaired CNS function
* Any condition that would interfere with the participants ability to perform behavioral research tasks
* Limitations with English that would interfere with understanding consent/assent, interview, or task instructions.
* NIMH IRP Employee family member

Amish Community healthy volunteer children \& adolescents:

INCLUSION CRITERIA:

* Age 8-17
* No serious physical or neurological symptoms or disorder by history

EXCLUSION CRITERIA:

* I.Q. \< 70
* Ongoing medical illness
* Neurological disorder (including seizures)
* Past or present substance abuse
* History of sexual abuse
* Limitations with English that would interfere with understanding consent/assent, interview or task instructions
* Past or present psychopathology in control subject or their first-degree relative
* NIMH IRP Employee family member

Amish Community adults who are parents of healthy volunteer children \& adolescents, healthy spouses of Amish adults with BD, or parents of adolescents with BD:

INCLUSION CRITERIA:

* Age 18-58
* No serious physical or neurological symptoms or disorder by history
* For Parents of child with BD or spouses of patient with BD: Spouse or offspring with BD

EXCLUSION CRITERIA:

* I.Q. \< 70
* Ongoing medical illness
* Neurological disorder (including seizures)
* Past or present substance abuse
* History of sexual abuse
* Limitations with English that would interfere with understanding consent/assent, interview or task instructions
* NIMH IRP Employee/family member
* For Healthy volunteers: Past or present psychopathology in participant or their first-degree relative
* For Parents of healthy volunteer children: Past or present psychopathology as in (4) above.

In addition, children with BD (Section B.1.) who wish to receive treatment, including discontinuation of medication while inpatients on the pediatric behavioral health unit at NIH, may be eligible for treatment if they meet the following additional criteria:

All inclusion criteria for B.1 (above)

Treatment failure as defined by current CGAS score \<60

The child s psychiatrist/treating physician agrees that a change in medication regimen is appropriate

EXCLUSION CRITERIA:

All exclusion criteria for B.1 (above)

Any contraindications for MRI scanning, plus claustrophobia or extreme separation anxiety

EXCLUSIONS for MRI Scanning:

* Pregnancy
* Substance abuse within two months of the initial evaluation, since alcohol and abused substances interfere with interpretation of fMRI and cognitive task data.
* Claustrophobia or anxiety that prevents participation in MRI
* Any serious medical condition or condition that interferes with fMRI scanning
* Metal in body which would make having an MRI scan unsafe, such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants or shrapnel fragments, or if you were a welder or metal worker, since there may be

small metal fragments in the eye

- Unable to lie comfortably on back for up to 90 minutes
C: * INCLUSION CRITERIA:

Inclusion criteria for both Interpretation Bias Training and Cognitive Behavioral Therapy Studies:

1. Age 8-17 years
2. Must be enrolled into NIMH DIRP protocol 02-M-0021, Characterization and Pathophysiology of Severe Mood and Behavioral Dysregulation in children and youth.
3. Must meet DSM 5 diagnostic criteria for DMDD which are (for CBT, must meet lifetime history of either DMDD or one of two core DMDD criteria \[b or c\]):

   * Must meet all of the following:

     1. Diagnosis must first be made between ages 6-18 years
     2. Abnormal mood (specifically, anger and/or irritability), present at least half of the day most days, and of sufficient severity to be noticeable by people in the child s environment (e.g. parents, teachers, peers).
     3. Compared to his/her peers, the child exhibits markedly increased reactivity to negative emotional stimuli that is manifest verbally or behaviorally. For example, the child responds to frustration with extended temper tantrums (inappropriate for age and/or precipitating event), verbal rages, and/or aggression toward people or property. Such events occur, on average, at least three times a week.
   * The symptoms in b and c above are currently present and have been present for at least 12 months without any symptom-free periods exceeding two months.
   * The onset of symptoms must be prior to age 10 years.
   * The symptoms are severe in at least one setting (e.g. violent outbursts, assaultiveness at home, school, or with peers). In addition, there are at least mild symptoms (verbal aggression) in a second setting.
4. Patients must be fluent in English

   1. All instruments have not been validated in other languages.
   2. Psychotherapy will be designed and conducted in English.
5. On the basis of record review and interviews with child and parent, the research team agrees that the child s response to his/her current treatment is no more than minimal (i.e. CGI-S of 3 or more).
6. Must have no planned changes in outpatient psychiatric treatment regimen, which can include psychotropic medications and/or psychotherapeutic interventions, two weeks prior to enrollment and throughout the three weeks of training and post-training assessment.

EXCLUSION CRITERIA:

Exclusion criteria both Interpretation Bias Training and Cognitive Behavioral Therapy Studies:

1. The individual exhibits any of these cardinal bipolar symptoms:

   1. Elevated or expansive mood.
   2. Grandiosity or inflated self-esteem.
   3. Decreased need for sleep.
   4. Increase in goal-directed activity (this can result in the excessive involvement in pleasurable activities that have a high potential for painful consequences).
   5. A history of hypomanic or manic symptoms that occurred in distinct episodes lasting more than 1 day.
2. Meets DSM 5 criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, Autism Spectrum Disorder, or posttraumatic stress disorder.
3. IQ\<70
4. The symptoms are due to the direct physiologic effects of a drug of abuse, or to a general medical or neurological condition.
5. Meets criteria for alcohol or substance abuse three months prior to enrollment.
6. Meets DSM 5 criteria for current major depressive disorder. The rationale for the exclusion of youth with MDD is because the two novel interventions being tested are contraindicated for those with major depressive disorder. However, there is no contraindication to participation for those with treated/resolved or remitted major depressive disorder; only those with a current diagnosis need to be excluded.
D: Inclusion Criteria:

1. Child has a confirmed diagnosis of FXS (\>200 CGG repeats on the FMR1 gene with evidence of aberrant methylation)
2. Child is male, between the ages of 3-10 years old
3. Child is reported to show self-injury, property destruction and/or aggression on at least a daily basis
4. The caregiver agrees to keep any therapies that the child receives (i.e., medications or other treatments) as stable as possible throughout involvement in the study
5. The family has a high-speed internet connection at home or lives in an area with 4G network coverage
6. Availability for one-hour daily telemedicine treatment sessions
7. Availability for in-home assessment totaling 8 hours across two consecutive days

Exclusion Criteria:

1. The child or caregiver has significant sensory impairments (e.g., blindness or deafness)
2. Non-English speaking
3. The child receives Applied Behavior Analysis services in excess of five hours per week
4. The child has a significant neurological condition (e.g., frequent seizures, brain injury, Tourette's syndrome) that would preclude participation
5. The child or caregiver has significant mobility issues
6. The child is currently participating in another research study that would preclude participation in the study

Answer: C