Irritability

Background: Irritability is defined as proneness to anger that may impair a person s ability to function. It is a common reason for why some children need mental health care. Yet no therapies have been developed just to target irritability. Researchers want to compare different types of therapy for irritability. Objective: To test different types of therapy for children and teens with severe irritability. Eligibility: People aged 8 to 16.5 years with severe irritability. Their parents are also needed. Design: Participants will have 28 study visits in 18 months. They will have a baseline visit. They will answer questions about their mood, behavior, and daily life. All parents and children will have 12 therapy sessions. Sessions will be once a week; they will last 30 to 60 minutes. Some of the child sessions may be done by telehealth. Each parent and child will have 1 of 3 therapy types: Exposure therapy (child). Participants will face things that make them angry. A therapist will help them practice managing their anger. Management therapy (parent). Therapists will coach parents on ways to manage their child s behaviors. Psychoeducation/supportive psychotherapy (child and/or parent). Participants will talk with therapists about their or their child s feelings and behaviors. They will list their problems and goals; build coping skills; learn to relax; improve communication; and work on managing stress. Sessions may be videotaped. Participants may opt out of being recorded. Participants will have phone calls every 2 weeks during therapy. They will answer questions about how they are doing. Follow-up calls will continue for 1 year after therapy.

Background: Irritability is defined as proneness to anger that may impair a person s ability to function. It is a common reason for why some children need mental health care. Yet no therapies have been developed just to target irritability. Researchers want to compare different types of therapy for irritability. Objective: To test different types of therapy for children and teens with severe irritability. Eligibility: People aged 8 to 16.5 years with severe irritability. Their parents are also needed. Design: Participants will have 28 study visits in 18 months. They will have a baseline visit. They will answer questions about their mood, behavior, and daily life. All parents and children will have 12 therapy sessions. Sessions will be once a week; they will last 30 to 60 minutes. Some of the child sessions may be done by telehealth. Each parent and child will have 1 of 3 therapy types: Exposure therapy (child). Participants will face things that make them angry. A therapist will help them practice managing their anger. Management therapy (parent). Therapists will coach parents on ways to manage their child s behaviors. Psychoeducation/supportive psychotherapy (child and/or parent). Participants will talk with therapists about their or their child s feelings and behaviors. They will list their problems and goals; build coping skills; learn to relax; improve communication; and work on managing stress. Sessions may be videotaped. Participants may opt out of being recorded. Participants will have phone calls every 2 weeks during therapy. They will answer questions about how they are doing. Follow-up calls will continue for 1 year after therapy.

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.

The purpose of this study is to determine if drinking a hot cup of coffee immediately before taking a 20-minute nap (the "Caffeine Nap") reduces the standard "grumpiness index" upon waking compared to drinking decaffeinated bean-water.

Background: Irritability can be defined as an unusually strong response to frustration; these responses may include severe temper outbursts and a constant grumpy mood. Irritability is a common symptom of many mental health disorders. Little is known about how the brain responds to frustration, and few treatments are available for this problem. Researchers want to know more about how the brain responds to frustration. Objective: To learn how the brain responds to frustration. Eligibility: Healthy adults aged 18 to 55 years. They must have been screened through studies 01-M-0254 or 17-M-0181. Design: Participants will have up to 3 study visits in 2 months. Each visit will last up to 4 hours. Visit 1: Participants will be screened. They will have a physical exam. They will complete questionnaires about how often and how easily they get angry or grumpy. They will be trained to use a device that measures hand grip. Visit 2: Participants will have a magnetic resonance imaging (MRI) scan. They will lie on a table that slides into a tube. Padding will hold their head still. Visit 3: Participants will undergo magnetoencephalography (MEG). A cone with detectors will be lowered over their head while they are seated. The MEG will measure the magnetic fields in the participant s brain both while they are resting and while they are doing the frustration task. For the task, they will hold a grip device in each hand. They will use the devices to pick 1 of 2 doors on a computer screen. The task has 3 parts. The participant s face will be filmed during this task.

The aim of this clinical trial is to evaluate whether AGENCIA, a brief psychological program supported by digital technology and artificial intelligence, can help reduce emotional and behavioral difficulties in adolescents aged 12 to 18. These difficulties may include irritability, impulsive behaviors, conflicts at home or at school, or difficulties in managing intense emotions. The study also aims to determine whether the effects are similar across adolescents with different symptom profiles or neurodevelopmental characteristics. Participants will be randomly assigned to one of three groups: AGENCIA Digital: a self-guided online version completed at home. AGENCIA in-person with a digital assistant: a clinician-delivered version supported by an interactive digital assistant to guide the exercises. Digital psychoeducation (control): a self-guided online program providing general information about adolescent well-being. The main research questions are: Does AGENCIA reduce overall emotional and behavioral difficulties? Does the program improve functioning, family accommodation, and personal agency (a young person's sense of being able to act and make changes)? Are the effects similar across adolescents with different profiles or neurodevelopmental characteristics? Participants will: * Complete three structured sessions depending on their assigned group. * Complete brief online questionnaires at baseline (T0), immediately after the sessions (T1), and at 1-month (T2) and 6-month (T3) follow-ups. * Receive brief phone calls during follow-ups to support questionnaire completion. A total of 465 adolescents will take part in the study. Participation is voluntary and does not replace usual clinical care. The study does not involve medication or invasive procedures, and all digital tools operate within secure institutional systems.

Purpose: Risk of severe psychopathology increases dramatically during adolescence, especially for females. Changes in ovarian steroids across the menstrual cycle produce windows of vulnerability to mood disturbances, particularly during the abrupt withdrawal of estradiol (E2) and progesterone (P4) prior to menses onset. Irrefutable evidence links stress with affective symptoms, potentially mediated by E2-related modifications of frontolimbic connectivity and prefrontal gamma-aminobutyric acid (GABA) inhibitory signaling. The primary objective of this project is to empirically test the impact of E2 and P4 change on vulnerable brain networks associated with irritability and other depressive symptoms in female adolescents at risk of suicide. Participants: The investigators will enroll 50 female adolescents ages 12-16 who are at risk of suicide (i.e., moderate depressive symptoms), and are eligible to receive oral contraceptives and undergo MRI imaging. Procedure: Using a randomized, placebo-controlled, cross-over design, participants will be studied under two conditions: 8 weeks of E2 and P4 stabilization (continuous combined oral contraceptive (COC) to prevent perimenstrual withdrawal) and 8 weeks of placebo, with a 1-month washout after each condition. Each condition will include: 1) daily samples of E2 and P4 urinary metabolites, 2) daily symptom ratings(e.g., irritability, negative affect and suicidal thoughts and behaviors (STBs)), and 3) a neuroimaging session with MRI and magnetic resonance spectroscopy (MRS).

Impulsive Aggression and chronic irritability (IACI) often occur together and are one of the most common reasons children present for behavioral health (BH) care. ADHD frequently associated with IACI as upwards of 50% of youth with ADHD manifest impairing IACI levels. IACI is the most common reason that children with ADHD are prescribed antipsychotics and admitted to inpatient BH units. Systematic dose optimization of CNS stimulants improves levels of IACI, reducing the need for these more intensive and burdensome treatments. However, response varies, with over half of children with ADHD showing meaningful improvement, upwards of 40% receiving minimal benefit and 3 to 10% exhibiting increased IACI levels. Symptom levels of ADHD or IACI and other demographic variables are of limited utility for predicting response, suggesting the need to move beyond symptoms in the search for treatment predictors. Youth with ADHD and IACI struggle with multiple aspects reinforcement learning (RL), defined as learning from interactions with the environment to reach a goal. Successful RL efforts tap multiple cognitive functions. In controlled laboratory tasks, youth with IACI and various BH disorders exhibit excessive behavioral and neural response to receiving reward (reward responsiveness), difficulty processing environmental cues to adapt behavior to meet a goal (set shifting/goal updating) and impaired ability to flexibly attend to relevant stimuli when blocked from a goal (frustrative nonreward). Event related potentials (ERP) are small electrical responses in the brain in response to specific events or stimuli measured by electroencephalogram (EEG) testing. ERPs exist that can serve as established neural measures of each of these cognitive functions offering a child friendly means to assess their contribution to observable levels of IACI. CNS stimulants improve functioning in these specific realms and impact associated ERPs to the degree that differences between ADHD and non-ADHD youth disappear. This study will examine the capacity of these ERPs to predict levels of IACI exhibited by children with ADHD when at home. Investigators will then assess if variability across children in the capacity of CNS stimulants to impact RL associated ERPs accounts for differences in the clinical effects of CNS stimulant medications to improve IACI at home using a multimethod battery integrating ERPs, parent report and task performance. Specifically, investigators will examine variance in the reward positivity (RewP) ERP when receiving reward feedback, the switch positivity (SwP) ERP measuring mental effort when cued to shift set and the change in P3b amplitude measuring attention allocation when transitioning from reward to nonreward on a go-no-go task. To achieve these aims, 136 children with ADHD and elevated IACI levels will have their CNS stimulant dose optimized over six weeks and then complete a two week within subjects crossover trial of placebo versus optimal dose. ERP collection will be completed within each blinded week. Parent ratings will be gathered 3 times per day including during peak and off-peak times of medication efficacy to capture the variance in IACI levels within the day and disentangle reports of worsening IACI related to loss of previously beneficial medication effects versus those most likely related to a direct adverse response to medication.

The goal of this clinical trial is to learn if adding an artificial intelligence (AI) application called to standard Behavioral Parent Training (BPT) helps families with children who have disruptive behavior problems. It will also help researchers understand if the app is easy to use and helpful for parents. The main question it aims to answer is: \- Is it feasible and acceptable for parents to use the AI app alongside their therapy sessions? The secondary questions it aims to answer are: * Does the app help reduce children's disruptive behaviors and irritability more than therapy alone? * Does using the app help lower stress, anxiety, and depression levels for the parents? Researchers will compare: 1. Standard BPT: Parents receive 8 weekly group training sessions (online). 2. BPT plus ParenteAI: Parents receive the same 8 weekly sessions plus 24/7 access to an AI virtual assistant for personalized support. Participants will: * Attend 8 weekly group training sessions. * Complete surveys about their child's behavior and their own well-being at baseline, after group training sessions 4 and 8, and 3 and 6 months after finalizing the group training. * If in the experimental group, use the ParenteAI app to get real-time coaching and support for managing their child's behavior at home. * Provide feedback on their experience and satisfaction with the program.

The goal of this clinical medicine study is to investigate how does antidepressant fluoxetine modulate anger processing in healthy young people . The main questions it aims is to answer are: 1. How does fluoxetine affect responses to anger-related stimuli such as words, faces, and autobiographical recall? 2. How does fluoxetine influence responses during frustration induction in frustrative non-reward and threat paradigms? 3. Does the effect manifest in physiological markers, including heart rate variability and facial expressions? Researchers will compare fluoxetine to a placebo to see if drug fluoxetine affects anger processing. Participants will: Take 20mg fluoxetine or a placebo every day for 7 days. Visit the university site for questionnaire and tasks assessments. Heart rate variability and facial expressions will be recorded in some of the tasks.

The Pain and Irritability of Unknown Origin (PIUO) Pathway is a clinical pathway that was developed to evaluate and manage unexplained pain and irritability for children with severe neurological impairments (SNI) who cannot verbally communicate 'where it hurts'. The investigators studied the usefulness of the Pathway with families and expert clinicians in 4 centres across Canada. The aim of this Phase 2 study is to determine whether this tool can transfer from hospital research centres into the community. The Pathway will be used by community pediatricians across British Columbia (BC) when they see patients with PIUO. The investigators want to know how well these pediatricians can follow the Pathway. The goal is to create a systematic, cohesive approach to enhance the clinical care for all children with complex medical needs experiencing PIUO.

It is known from the literature that treatment with antipsychotic drugs (AP) induces, even before changes in blood chemistry parameters, changes in gene transcription that are evident at the level of peripheral blood mononuclear cells. In this pilot study we intend to evaluate the transcriptomic profile of children and adolescents who are undergoing treatment with antipsychotics and show metabolic disorders, in order to compare it to the profile of similar patients who do not use antipsychotics, but show metabolic disorders, or who use antipsychotics, but do not show metabolic disorders. The hypothesis is that a different transcriptomic profile can be identified between the three populations under study, such as to allow to hypothesize that a series of transcripts can be used as early biomarkers of whether treatment with antipsychotics can induce metabolic disorders in the individual patient or not. This information could be used to improve the management of antipsychotic therapies in the direction of personalized medicine, reducing metabolic risks.