Child & Adolescent Psychiatrist Childhood Rage Diagnosis and Treatment Strategies for Severe Mood Dysregulation E. John Kuhnley, MD Child & Adolescent Psychiatrist Lynchburg, Virginia

OBJECTIVES Disclosures: None 1) Understand and differentiate the various presentations of rage in children and adolescents. 2) Review/learn the interplay of genetics, neurobiology, development, environment, psychological factors, social interaction factors, spiritual factors, and other factors influencing presentation of rage in children and adolescents. 3) Identify an integrative treatment approach (medication and non-medication strategies) for conditions presenting with rage (including Oppositional Defiant Disorder, Explosive behavior, Severe Mood Dysregulation, ADHD, Anxiety Disorders, Bipolar Disorder and other mood disorders). 1) Understand and differentiate the various presentations of rage in children and adolescents. 2) Review/learn the interplay of genetics, neurobiology, development, environment, psychological factors, social interaction factors, spiritual factors, and other factors influencing presentation of rage in children and adolescents. 3) Identify an integrative treatment approach (medication and non-medication strategies) for conditions presenting with rage (including Oppositional Defiant Disorder, Explosive behavior, Severe Mood Dysregulation, ADHD, Anxiety Disorders, Bipolar Disorder and other mood disorders). Disclosures: None

The Demon Child In her own words. Picture from website of Clear View Counseling, 4140 W. Charleston Blvd., Las Vegas, Nevada 89102, (702)254-4883 http://www.clearviewcounseling.com/Anger.php

30 Years Later She was happily married and they have a healthy grown child whom she made certain has NEVER had to experience abuse, despite the predictions that abused children like herself often grow up to become abusive themselves She was a beloved and successful professional counselor who dedicated herself to helping children, so many of whom have experienced abuse She died of cancer in 2013 and is missed by family, friends, and clients

Clinical Take-Home Messages Parents don’t tell us everything Patients don’t tell us everything Collateral sources don’t tell us everything We must obtain information from multiple sources, put it together and figure it out Rage and mood swings seldom equate to Bipolar Disorder and may indicate many underlying possibilities

ANGER RAGE FURY FRUSTRATION IRRITATION AGITATION DISAPPOINTMENT ANNOYANCE DISTRACTION DISAPPOINTMENT FRUSTRATION IRRITATION AGITATION ANGER RAGE FURY Continuum: Annoyance / Disappointment / Distraction Frustration / Irritation / Agitation Anger / Rage

ANGER A normal emotion in reaction to perceived: Threat of harm to self, others, property Incitement of the fight/fight/freeze response Being wronged, offended, challenged, shamed, or unfairly treated or witnessing such Types of anger include: Situational / episodic Dispositional / characterological Purposeful / manipulative A normal emotion in reaction to perceived: Threat of harm to self, others, property Incitement of the fight/fight/freeze response Being wronged, offended, challenged, shamed, or unfairly treated or witnessing such Types of anger: Situational / episodic Dispositional / characterological Anger causes a loss in self-monitoring capacity and objective observability

ANGER Anger may cause a loss in self-monitoring capacity and objective observability Anger may be internalized or externalized Anger may have physical correlates such as increases in heart rate, blood pressure, and levels of adrenaline and noradrenaline. The Incredible Hulk cartoon

The Limbic System Structures including: Functions including: Anterior thalamic nuclei Hippocampus, Amygdala Septum Limbic cortex and fornix, Functions including: Emotion (anger, fear, etc.) Behavior Long term memory, and Olfaction (sense of smell)

In neuroimaging studies of anger, the most consistently activated region of the brain was the lateral orbitofrontal cortex. International Handbook of Anger. Chapt 4: Constructing a Neurology of Anger. Michael Potegal and Gerhard Stemmler. 2010 In neuroimaging studies of anger, the most consistently activated region of the brain was the lateral orbitofrontal cortex.[45] This region is associated with approach motivation and positive affective processes. http://bungelab.berkeley.edu/kidscorner/kidscorner/glossary.html International Handbook of Anger. Chapt 4: Constructing a Neurology of Anger. Michael Potegal and Gerhard Stemmler. 2010

Impulsive and explosive, Occurring in discrete episodes Both the popular and the scientific literature describe "RAGE BEHAVIOR" as Impulsive and explosive, Occurring in discrete episodes Showing a highly emotional, agitated state with little thinking and no planning. Both the popular and the scientific literature describe "RAGE BEHAVIOR" as Impulsive and explosive, Occurring in discrete episodes Showing a highly emotional, agitated state with little thinking and no planning. RAGE BEHAVIOR - UHS Neurobehavioral Systems RAGE BEHAVIOR - UHS Neurobehavioral Systems

Dynamic Interplay Genetics (Mutable) Environment Experiences Illnesses Presentation of anger and/or rage in / by an individual results from a dynamic interplay of factors, many of which are depicted here. Genetics (Mutable) Social Interactions, Attachment Spirituality Psychological Factors: Temperament, perceptions, coping mechanisms, and attitudes Individual’s Development “Learning” Environment Experiences Illnesses Dynamic Interplay Presentation of anger and/or rage in by an individual results from a dynamic interplay of factors, many of which are depicted here. Genetics (Mutable) Social Interactions, Attachment Spirituality Psychological Factors: Temperament, perceptions, coping mechanisms, and attitudes Individual’s Development “Learning” Environment Experiences Illnesses Examples: A child may suppress expression of rage when father is present but let loose when he is not present. A child may suppress expression of rage at home but not at school OR vice versa. A child may learn that expressing rage gets him what he wants and reinforces the behavior. A child may experience guilt and shame from expression of rage, even if beyond the child’s control, resulting in feeling of unworthiness in the eyes of God. Parents may use guilt and shame as an attempt to get the child to control expression of anger and gare, even if beyond the child’s control, and this may backfire with result of low self-esteem and feelings of unworthiness by the child. A father may train a child that he does not have to listen to mother and other children and encourage displays of anger and rage. Genes code for neurotransmitters, receptors and other biological processes involved in overall function and there are many genetic variations that may influence slowing or malfunction of various processes. Life experiences may produce genetic variations that may have impact on function. Counseling may assist a child in developing behavior habits, thinking, and internal scripts that assist in executive function control. Psychological factors including the child’s perceptions, coping mechanisms, and attitudes influence how he experiences the world and reacts or responds to the world.

Examples: A child may suppress expression of rage when father is present but let loose when he is not present. A child may suppress expression of rage at home but not at school OR vice versa. A child may learn that expressing rage gets him what he wants and this reinforces the behavior. A child may experience guilt and shame from expression of rage, even if beyond the child’s control, resulting in feeling of unworthiness in the eyes of God. Parents may use guilt and shame as an attempt to get the child to control expression of anger and rage, even if beyond the child’s control, and this may backfire with result of low self-esteem and feelings of unworthiness by the child.

Examples: A father may train a child that he does not have to listen to mother and other children and encourage displays of anger and rage. Genes code for neurotransmitters, receptors and other biological processes involved in overall function and there are many genetic variations that may influence slowing or malfunction of various processes. Life experiences may produce genetic variations that may have impact on function. Counseling may assist a child in developing behavior habits, thinking, and internal scripts that assist in executive function control. Psychological factors including the child’s perceptions, coping mechanisms, and attitudes influence how he experiences the world and reacts or responds to the world.

RAGE - Psychological Primitive emotion conceptualized as a preverbal, precognition psychological defense mechanism stemming from perceived failure of need fulfillment Rage is construed as an attempt to summon help by an infant who experiences terror and whose very survival feels under threat. Parker Hall, 2008, Anger, Rage and Relationship: An Empathic Approach to Anger Management, Routledge

John Bowlby – Attachment Theory Attachment theory is an ideal lens to understand anger. John Bowlby first witnessed the effects of infants separated from their mothers in a hospital setting, when intense displays of anger were followed by despair and detachment (1988). He proposed that the function of the anger was meant to be a signal to the parent to become available to provide comfort and support, soothing the fear and anxiety associated with separation, at a time when self-soothing capacities are not yet developed. And depending on the response of the caregiver(s), the healthy expression of anger can become dysfunctional due to insensitive or fear-inducing responses by the parents. Anger - Attachment and Neurobiological Perspectives Daniel Sonkin, Ph.D. Licensed Marriage and Family Therapist Daniel Sonkin, Ph.D.

Mary Ainsworth - Attachment Mary Ainsworth identified three infant attachment strategies, on a continuum of deactivation to hyperactivation of the attachment behavioral system (Ainsworth, et. al., 1978). On one end of the continuum, “A-babies”, also labeled “anxious-avoidant”, deactivated visual demonstrations of distress during separations and reunions with attachment figures in the Strange Situation (the method she developed to assess attachment behaviors). Avoidant babies sacrificed proximity to a caretaker for chronic exploration. Through many interactions with their caregiver, they learned that seeking proximity to a consistently insensitive parent did not lead to alleviation of distress. They developed a mental representation that others are not likely to alleviate distress; therefore, rigid self-sufficiency is the only option, even though the natural instinct is to seek proximity to others for soothing. A fourth category, termed “Can Not Classify”, seemed to show both deactivating and hyperactivating strategies. This category was not more fully understood until Mary Main and Carol Solomon (1986) reexamined this group. The reason for this disorganized strategy (approaching and avoiding proximity at the same time), was because the vast majority of these infants were experiencing abuse by their caregiver. The person to whom they looked to for soothing, was also the source of their fear. They were experiencing fear without solution. Daniel Sonkin, Ph.D.

Mary Ainsworth - Attachment At the other end of the continuum, “C-babies”, also labeled “anxious-resistant”, hyperactivated attachment distress during time of separations and reunions with attachment figures. These infants sacrificed exploration for the sake of chronic proximity seeking. Through many interactions with their caregiver(s), they learned that they had to keep a hypervigilant watch over their inconsistently insensitive parent, in hope that the parent would respond in a sensitive manner. They developed a mental representation that they were unable to self-sooth and therefore need others for that purpose. A fourth category, termed “Can Not Classify”, seemed to show both deactivating and hyperactivating strategies. This category was not more fully understood until Mary Main and Carol Solomon (1986) reexamined this group. The reason for this disorganized strategy (approaching and avoiding proximity at the same time), was because the vast majority of these infants were experiencing abuse by their caregiver. The person to whom they looked to for soothing, was also the source of their fear. They were experiencing fear without solution. Daniel Sonkin, Ph.D.

Mary Ainsworth - Attachment In the middle are “B-babies”, also labeled “secure”, who are more flexible in their response to separation distress. They curtail exploration when their attachment behavioral system is activated, and can seek and respond to soothing offered from caregivers, which in turn deactivates the distress system so that they can return to exploration and play. A fourth category, termed “Can Not Classify”, seemed to show both deactivating and hyperactivating strategies. They were experiencing fear without solution. A fourth category, termed “Can Not Classify”, seemed to show both deactivating and hyperactivating strategies. This category was not more fully understood until Mary Main and Carol Solomon (1986) reexamined this group. The reason for this disorganized strategy (approaching and avoiding proximity at the same time), was because the vast majority of these infants were experiencing abuse by their caregiver. The person to whom they looked to for soothing, was also the source of their fear. They were experiencing fear without solution. Daniel Sonkin, Ph.D.

Children in all four attachment categories experience anger and frustration, but it is how their caregiver(s) respond(s) to their distress, that in part determines how the child ultimately copes with these emotions. Daniel Sonkin, Ph.D.

Avoidant children deactivate distress and therefore anger is more likely to be expressed in more indirect ways. Resistant children are more likely to be chronically angry, and to express other emotions through their anger. Disorganized children may get so overwhelmed with emotional flooding, that they could dissociate or become aggressive toward self or others. Secure children do become angry too, but they are more likely to express it directly to others. When the source of anger is not available they can rely on mental representations that allow for self-soothing and returning toward a state of emotional well-being. Insecure children lack a positive mental representation of soothing, so their mental representations are likely to contribute to more anger, rather than less (Mikulincer and Shaver, 2007). Daniel Sonkin, Ph.D.

The American psychologist Albert Ellis has suggested that anger, rage, and fury partly have roots in the philosophical meanings and assumptions through which human beings interpret transgression. The American psychologist Albert Ellis has suggested that anger, rage, and fury partly have roots in the philosophical meanings and assumptions through which human beings interpret transgression.[55] Ellis, Albert (2001). Overcoming Destructive Beliefs, Feelings, and Behaviors: New Directions for Rational Emotive Behavior Therapy. Promotheus Books.

Genesis 3: The Fall Expulsion from Paradise; marble bas-relief by Lorenzo Maitani on the left pier of the façade of the cathedral; Orvieto, Italy Note one reference regarding expulsion from the garden: www.gotquestions.org - Bible Questions Answered Question: "What is the meaning of the tree of life?" Answer: The tree of life, referred to in Genesis, is the symbol of God’s provision for immortality in the Garden of Eden. Of all the trees that were in the Garden of Eden, two were named for their great importance, but just as one—the tree of life—was a blessing to Adam and Eve, the other was to become a curse for all of their posterity. “And the Lord God made all kinds of trees grow out of the ground – trees that were pleasing to the eye and good for food. In the middle of the garden were the tree of life and the tree of the knowledge of good and evil” (Genesis 2:9). The Lord told Adam that he was free to eat the fruit of any tree in the Garden, except for the tree of the knowledge of good and evil for by doing so he would surely die (Genesis 3:16-17). The tree of life was provided to be continuous reminder that immortality was a consequence of obedience. As long as Adam and Eve were obedient and did not eat of the tree of the knowledge of good and evil, they had access to the tree of life. Once they sinned, they were driven from the Garden, and God placed an angel with a flaming sword to guard the tree of life so they would no longer have access to it. Eternal life was now no longer theirs. Just as God had warned, they died, and through Adam all men after him would die (Romans 5:12). By barring access to the tree of life, God showed compassion in His omniscience. Knowing that because of sin, life would be filled with sorrow and toil, He graciously limited the number of years men would live. To live eternally in a sinful state with its results—pain, disease, heartache, toil, and grief—would mean endless agony for humanity, with no hope of the relief that comes with death. By limiting our lifespan, God gives us enough time to come to know Him and His provision for eternal life through Christ, but spares us the misery of an endless existence in a sinful condition. Because God knew that Adam would fail the conditions of his immortality, He provided for One who would redeem fallen mankind. Through one man, Adam, sin entered the world, but through another Man, Jesus Christ, redemption through the forgiveness of sin is available to all (Romans 5:17). Those who avail themselves of the sacrifice of Christ on the cross will see the tree of life again, for it stands in the middle of the Holy City, the New Jerusalem (Revelation 21:2, 22:1-2). Its water is the constant flow of everlasting life from God’s throne to God’s people.

(The verses refer to God’s anger but also his resultant mercy.) Artist Meister der Bibel des Patrice Léon Title Deutsch: Bibel des Patrice Léon, Szene: Moses empfängt die Gesetzestafeln auf dem Berge Sinaii, BAV Reg. gr. 1, Fol. 155v Deuteronomy 9 [18] And I fell down before the LORD, as at the first, forty days and forty nights: I did neither eat bread, nor drink water, because of all your sins which ye sinned, in doing wickedly in the sight of the LORD, to provoke him to anger. [19] For I was afraid of the anger and hot displeasure, wherewith the LORD was wroth against you to destroy you. But the LORD hearkened unto me at that time also. (The verses refer to God’s anger but also his resultant mercy.) Deuteronomy 9 [18] And I fell down before the LORD, as at the first, forty days and forty nights: I did neither eat bread, nor drink water, because of all your sins which ye sinned, in doing wickedly in the sight of the LORD, to provoke him to anger. [19] For I was afraid of the anger and hot displeasure, wherewith the LORD was wroth against you to destroy you. But the LORD hearkened unto me at that time also. The verses refer to God’s anger but also his resultant mercy.

Christians believe in God's anger in the sight of evil Christians believe in God's anger in the sight of evil. This anger is not inconsistent with God's love, as demonstrated in the Gospel where the righteous indignation of Christ is shown when he drives the moneychangers from the temple. Christians believe that those who reject His revealed Word, Jesus, condemn themselves, and are not condemned by the wrath of God.[71] Shailer Mathews, Gerald Birney Smith, A Dictionary of Religion and Ethics, Kessinger Publishing, p.17

Matthew 21:12 And Jesus went into the temple of God, and cast out all of them that sold and bought in the temple, and overthrew the tables of the moneychangers, and the seats of them that sold doves, Giotto di Bondone (1267-1337), Cappella Scrovegni a Padova, Life of Christ, Expulsion of the Money-changers from the Temple

Gene variations produce vulnerabilities for various conditions including anxiety, irritability, inflammation, etc. Genes affect neurotransmitter and receptor functions, etc. Most psychiatric disorders are highly heritable Genetics

Protective Factors VS. Risk Factors HEALTH IMPAIRMENT

Causes of Irritability Normal Development Adjustments Preschoolers and Adolescents Nutritional Deprivation/Inadequacy Psychosocial Circumstances/Interactions Traumatic Experiences/Abuse Sleep Deprivation Allergic Conditions Psychiatric Conditions Substance Use/withdrawal Medical Conditions Inflammation Medications Toxins Irritability may fluctuate during normal developmental transitions: Pre-school and Adolescence.

Childhood Chronic Irritability and the Pathophysiology of Mental Illness – NIMH 2014 Irritability can be classified as a mood state, clinical symptom, or temperamental trait. Irritability is variably defined and measured in terms of anger, response to frustration, and reactive aggression. One formulation suggests that irritability is a trait presentation of chronic anger, and that irritability is characterized by a decreased threshold for, and aberrant responses to frustration, where frustration is the emotional response to blocked goal attainment. In addition, irritability can also be conceptualized in terms of aberrant approach responses to threat; by definition, then, reactive aggression (i.e., aggressive responses to threat) is characteristic of irritable people. NIMH: Childhood Chronic Irritability and the Pathophysiology of Mental Illness; http://www.nimh.nih.gov/research-priorities/scientific-meetings/2014/childhood-chronic-irritability/childhood-chronic-irritability-and-the-pathophysiology-of-mental-illness.shtml

SCHOOL HOME The World Of the Child CHILD PERCEPTION © Kuhnley, 1996 Teacher- Child Relationship Academic Performance Cognitive Development Behavioral Physical Sibling Parent- Extended Family, Community, Spirituality Self Concept Self Esteem Attitude & Temperament Expectations Of Outcome Peer Interactions The World Of the Child SCHOOL PERCEPTION DEVELOPMENT We must remember we are dealing with a child. I have a poster from the 1970s that shows a child with a slingshot behind his back and the caption, “Please be patient, God isn’t finished with me yet.” In our zeal to make children better than we are all too often we expect more from them than we might expect from ourselves or other adults who have had years to develop skills. HOME © Kuhnley, 1996

Diagnosis in Clinical Practice Start by allowing the patient to express concerns; ask questions to facilitate expression Obtain the patients’ (and collateral sources) accounts “In Their Own Words” rather than asking criteria they can endorse The clinical interview must elicit and elucidate the patient’s experience and symptoms and thus lead us to diagnostic criteria; then the diagnostic criteria guide us to clarification/confirmation, rather than the diagnostic criteria guiding the interview Example: Rather than ask if they have decreased need for sleep, ask if they are experiencing any problems with sleep and then ask questions that elaborate or elucidate the problem.

MOOD SWINGS Bipolar Disorder is all the rage but all rage is not bipolar disorder. Contrary to current popular belief, Mood Swings do not equate with Bipolar Disorder and are more likely to be something else, such as comorbid ADHD + ODD. Accurate diagnosis is essential for effective treatment. ADHD = Attention-Deficit/Hyperactivity Disorder ODD = Oppositional Defiant Disorder

“Mood swings are analogous to a fever in pediatrics—they indicate something potentially is wrong with the patient, but are not diagnostic as an isolated symptom.” The differential diagnosis of “mood swings” is important because they are a common presenting symptom of many children and adolescents with mood and behavioral disorders. Mood swings often occur in children and adolescents with ADHD, oppositional defiant disorder (ODD), developmental disorders, depressive disorders, BD, anxiety disorders, and conduct disorders. Mood swings are analogous to a fever in pediatrics—they indicate something potentially is wrong with the patient, but are not diagnostic as an isolated symptom. Mood swings in children are common, nonspecific symptoms that more often are a sign of anxiety or behavioral disorders than BD. This article discusses the differential diagnosis of mood swings in children and adolescents and how to best screen and diagnose these patients. Mood swings is a popular term that is nonspecific and not part of DSM-IV-TR diagnostic criteria for BD. The complaint of “mood swings” may reflect severe mood lability of pediatric patients with BD. This mood lability is best described by the Kiddie-Mania Rating Scale (K-MRS) developed by Axelson and colleagues as “rapid mood variation with several mood states within a brief period of time which appears internally driven without regard to the circumstance.”1 Robert A. Kowatch, MD, PhD  Professor of Psychiatry and Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH Current Psychiatry Vol. 10, No. 02 / February 2011 Not all mood swings are bipolar disorder Robert A. Kowatch, MD, PhD  Professor of Psychiatry and Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH

MOOD SWINGS “Mood swings” is a popular term that is nonspecific and not part of DSM-IV-TR diagnostic criteria for Bipolar Disorder (BD). The complaint of “mood swings” may reflect severe mood lability of pediatric patients with BD. The mood lability of BD is best described by the Kiddie-Mania Rating Scale (K-MRS) developed by Axelson and colleagues as: “Rapid mood variation with several mood states within a brief period of time which appears internally driven without regard to the circumstance.”1 [Kowatch] Source?

Differential Diagnosis and Comorbidity Attention-Deficit/Hyperactivity Disorder (ADHD) Oppositional Defiant Disorder (ODD) Bipolar Disorder (BD) DMDD: Disruptive Mood Dysregulation Disorder Major Depressive Disorder (MDD) Anxiety Disorders Autism Spectrum Disorders (ASD) Differential Diagnosis and Comorbidity Differential Diagnosis & Comorbidity BD = Bipolar Disorder DMDD = DSM-5 = Disruptive Mood Dysregulation Disorder * SMD, Severe Mood Disorder, is not a diagnosis. TDD = Temper Dysregulation Disorder was proposed for DSM-V.

The most common diagnoses among patients with mood swings FREQUENCY DIAGNOSIS 39% ADHD 15% ODD with ADHD ANXIETY D/O (GAD) 12% BIPOLAR DISORDER 10% SECONDARY MOOD DISORDER (eg. Fetal Alcohol Spectrum Disorder) 3% PDD, ASPERGER’S (> now ASD or Autism Spectrum Disorder) The most common diagnoses among patients with the chief complaint of mood swings were ADHD (39%); ODD with ADHD (15%); an anxiety disorder, usually generalized anxiety disorder (GAD) (15%); BD (12%); and a secondary mood disorder, usually fetal alcohol spectrum disorder (10%). Current Psychiatry Vol. 10, No. 02 / February 2011 Not all mood swings are bipolar disorder How to evaluate children with mood lability Robert A. Kowatch, MD, PhD  Kowatch, et al, Current Psychiatry Vol. 10, No. 02 / February 2011

Aggression in Various Conditions ODD = common; purposeful, not impulsive; fail to take responsibility ADHD = less common; impulsive, less purposeful; remorseful ANX = not common; fight or flight reaction to fear; impulsive or reactive during episodes of anxiety; remorseful; more directed inward than outward MDD = not common; reactive during episodes of depression; remorseful; more directed inward than outward BD = episodic and may be sustained during episode DMDD = non-episodic rages, i.e. not a change from baseline chronic irritability

Attention-Deficit/Hyperactivity Disorder (ADHD) Key Features: Inattention Impulsivity Hyperactivity (in 60%) Low Frustration Tolerance (important but not a diagnostic criterion)

Oppositional Defiant Disorder (ODD) (DSM5) A recurrent pattern of angry/irritable mood, argumentative/defiant behavior, or vindictiveness lasting at least 6 months. To fulfill the diagnosis, an individual must have at least 4 symptoms from the following categories: 1) Angry/Irritable Mood • Often loses temper • Often touchy or easily annoyed • Often angry and resentful 2) Argumentative/Defiant Behavior • Often argues with authority figures or with adults (if a child or adolescent) • Often actively defies or refuses to comply with requests from authority figures • Often deliberately annoys others • Often blames others for his or her mistakes or poor behavior 3) Vindictiveness • Has been spiteful or vindictive at least twice within the past 6 months Symptoms are almost always present at home and may or may not be present in the community and at school. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5).

Normal Anxiety versus Anxiety Disorder Normal ANXIETY & WORRY The apprehensive anticipation of future danger or misfortune Anxiety suggests feelings of fear and apprehension Worry implies persistent doubt or fear; to torment oneself with or suffer from disturbing thoughts; fret. Do not cause significant distress or interference with day-to-day activity Anxiety Disorder: EXCESSIVE FEAR OR WORRY THAT IS RECURRENT AND LONG-LASTING THE SYMPTOMS CAUSE DISTRESS AND / OR INTERFERE WITH DAY-TO-DAY ACTIVITY

Physiology of fear—when a threat is perceived, the senses dispatch signals to the cerebral cortex (the thinking part of the brain) and the amygdala (which sets off a very rapid, automatic response that mobilizes the brain and body to deal with the danger at hand). The amygdala swings into action before the cortex is aware of what’s happening. The amygdala is activated not only by danger, but also by the unexpected. The amygdala’s rapid response system causes release of stress hormones in to the blood—the heart beats faster, and blood is diverted from internal organs to the muscles, where it may be needed for quick action. Meanwhile, glucose pours into the bloodstream, where it supplies the energy necessary for fighting or fleeing. To protect the person in future confrontations with the same threat, a blueprint of the learned fear response is etched onto the amygdala. In the face of real danger, the fear response serves a protective function, and in a dire emergency, it can be a literal life-saver. The problem arises when frightening or unexpected events prime a person’s brain to overreact to relatively harmless situations—serving as a hindrance rather than a help. Some research indicates that different anxiety disorders may be associated with activation in different parts of the amygdala. After activation of the amygdala, sensory information about the threat soon reaches the cerebral cortex and the person is able to rationally appraise the situation. The goal of CBT is to improve the accuracy of such appraisals. Ultimately, the aim is to increase cognitive control over the person’s fear response. Preston, JD et al, Handbook of Clinical Psychopharmacology for Therapists, 4th Ed. 2006

Difficulty with focusing of attention Dizziness and light-headedness In all anxiety disorders, physical symptoms are a central feature of the "flight or fight" response: Rapid heart rate Need to over-breathe Tremor and shaking Nausea Sweating Difficulty with focusing of attention Dizziness and light-headedness Tingling and numbness

Disruptive Mood Dysregulation Disorder 296. 99 (F34 Disruptive Mood Dysregulation Disorder 296.99 (F34.8) Diagnostic Features The core feature of disruptive mood dysregulation disorder is chronic, severe persistent irritability. This severe irritability has two prominent clinical manifestations, the first of which is frequent temper outbursts. These outbursts typically occur in response to frustration and can be verbal or behavioral (the latter in the form of aggression against property, self, or others). They must occur frequently (i.e., on average, three or more times per week) (Criterion C) over at least 1 year in at least two settings (Criteria E and F), such as in the home and at school, and they must be developmentally inappropriate (Criterion B). The second manifestation of severe irritability consists of chronic, persistently irritable or angry mood that is present between the severe temper outbursts. This irritable or angry mood must be characteristic of the child, being present most of the day, nearly every day, and noticeable by others in the child's environment (Criterion D). DSM-5, APA

Psychological Processes and Neural Circuits Hypothesized to Contribute to Pathologic Irritability ACC=anterior cingulate cortex; PFC=prefrontal cortex; NAcc=nucleus accumbens Severe Mood Dysregulation, Irritability, and the Diagnostic Boundaries of Bipolar Disorder in Youths, Ellen Leibenluft, M.D. , Am J Psychiatry 2011; 168:129-142 By “context-sensitive”, we mean that the scripts were developed and used in the classroom settings where the participants were expected to participate. Context = 1. The circumstances that form the setting for an event, statement, or idea, and in terms of which it can be fully understood and assessed. Leibenluft, 2011

Amplification of Frustration Dysregulated Attention- Emotion Interactions Decreased threshold Increases Propensity To Frustration Goal Attainment Blocked Misinterpretation of Emotional Stimuli Increased Irritability/ Behavioral Dyscontrol Frustration Decreased Context- Sensitive Regulation Increased Probability

The anterior cingulate cortex and medial frontal gyrus—both Ellen Leibenluft, M.D. The anterior cingulate cortex and medial frontal gyrus—both hyperactivated in children with SMD (Severe Mood Dysregulation) following negative feedback—were the same areas activated in healthy control children following positive feedback. “It makes you think about cognitive training or therapies that could perhaps train children with SMD to pay greater attention to positive feedback and less attention to negative feedback,” Leibenluft said. Psychiatric News September 16, 2011, Volume 46 Number 18 Page 17, © American Psychiatric Association Clinical & Research News Severe Irritability May Signal Syndrome Apart From Bipolar, Mark Moran

Functional brain imaging studies Functional brain imaging studies are turning up circuitry differences between such seemingly overlapping disorders during emotional processing. In one recent fMRI study, while children rated their subjective fearfulness of neutral faces, the amygdala, the brain’s fear hub, Over-activated in ADHD, Under-activated in Severe Mood Dysregulation and Activated normally in Bipolar Disorder. These results suggest that we may be able to use the tools of clinical neuroscience to disentangle these various syndromes to help clinicians provide children with the best care. Amygdala activation during emotion processing of neutral faces in children with severe mood dysregulation versus ADHD or bipolar disorder. Brotman MA, Rich BA, Guyer AE, Lunsford JR, Horsey SE, Reising MM, Thomas LA, Fromm SJ, Towbin K, Pine DS, Leibenluft E. Am J Psychiatry. 2010 Jan;167(1):61-9. Epub 2009 Nov 16.PMID: 19917597 Amygdala activation during emotion processing of neutral faces in children with severe mood dysregulation versus ADHD or bipolar disorder. Brotman MA, Rich BA, Guyer AE, Lunsford JR, Horsey SE, Reising MM, Thomas LA, Fromm SJ, Towbin K, Pine DS, Leibenluft E. Am J Psychiatry. 2010 Jan;167(1):61-9. Epub 2009 Nov 16.PMID: 19917597

Rages--what are they and who has them? Conclusions: Psychiatrically hospitalized children with multiple rages have complex, chronic neuropsychiatric disorders and have failed prior conventional treatment. One third of children with rages had been given a bipolar diagnosis prior to admission. However, only 9% of children with rages were given that diagnosis after careful observation. Title: Rages--what are they and who has them?(Report) Pub: Journal of Child and Adolescent Psychopharmacology  Detail: Gabrielle A. Carlson, Michael Potegal, David Margulies, Zinoviy Gutkovich and Joann Basile. 19.3 (July 2009): p281(8). (6431 words)  Gabrielle A. Carlson, MD

Bipolar Disorder Not a 'Quick and Dirty' Diagnosis Although some children are being misdiagnosed as having BD, the opposite is also true. There are many children, he said, who have BD but whose conditions are misdiagnosed and treated inappropriately. "This is something we need to be aware of because bipolar seriously affects the normal development of a child and increases their risk of suicide, substance abuse, and psychosocial problems. Early recognition and appropriate treatment are most important.” Deborah Brauser Bipolar Disorder Not a 'Quick and Dirty' Diagnosis June 22, 2011 (Pittsburgh, Pennsylvania) — A major issue facing the field of psychiatry today may not be that children in the United States are being overdiagnosed with bipolar disorder (BD) but that many clinicians do not truly understand the complexities of this type of diagnosis. Gabrielle A. Carlson, MD, professor of psychiatry and pediatrics and director of the Child and Adolescent Psychiatry Department at the Stony Brook University School of Medicine in New York, said that no formula currently exists for accurately diagnosing BD in children. "A certain amount of humility is needed, and it is extremely important to clarify symptoms. Remember: context matters," Dr. Carlson told delegates attending the Ninth International Conference on Bipolar Disorder. Boris Birmaher, MD, professor of psychiatry and endowed chair in early-onset bipolar disease at the University of Pittsburgh School of Medicine and Western Psychiatric Institute and Clinic in Pennsylvania, agreed. "As a field, we're also looking at the issues of periodicity vs chronicity in bipolar disorder (in our practice we require that a child has definite episodes), the definition of rapid cycling, and the differences between narrow vs broad bipolar disorders. During his presentation, he said a diagnosis of BD can be difficult because it is highly comorbid and overlaps with symptoms of other illnesses, including attention-deficit/hyperactivity disorder (ADHD). "The big questions today are: What is the prevalence of bipolar in children? Is it more prevalent in the US than in other countries?" said Dr. Birmaher. United States on Par With Other Countries He discussed a new analysis published online May 31 in the Journal of Clinical Psychiatry that assessed 12 epidemiologic studies conducted between 1985 and 2007. The investigators evaluated the prevalence of pediatric BD in children from 8 countries between the ages of 7 and 21 years and found diagnosis rates ranged from 0% (in Ireland) to 3%, the same range found in the United States. "Another study that included a very broad definition of manic symptoms found that that rate could go up to 5%. But still, all of this shows that we are not very different from other countries," said Dr. Birmaher. However, a previous study (Arch Gen Psychiatry. 2007;64:1032-1039) showed that the number of physician visits ending in a diagnosis of pediatric bipolar in the United States increased significantly during 10 years. "There was a 40-fold increase in the rate of visits for these children compared to adults, but we need to be careful to look at the absolute numbers. For example, if you go from 1 diagnosis to 2, that's an increase of 100%," Dr. Birmaher explained. A 2010 national trends study (Bipolar Disorders. 2010;12:155-162) showed rates of BD diagnoses increased from 1.13 to 1.91 per 100,000 inpatients in Germany from 2000 to 2007. "This was technically an increase of 68%, but really it was only up from 1 to 2 per 100,000 people," said Dr. Birmaher. Pendulum Can Swing Both Ways "It does not seem that the prevalence of bipolar 1 or 2 is higher in the US, but the diagnosis of subsyndromal forms is higher than in other countries." "Pediatric bipolar exists, but we need to be careful because its diagnosis can be difficult," he said. Dr. Birmaher added that it is especially challenging when trying to identify core symptoms, such as grandiosity and elation in young children. He noted that although some children are being misdiagnosed as having BD, the opposite is also true. There are many children, he said, who have BD but whose conditions are misdiagnosed and treated inappropriately. "This is something we need to be aware of because bipolar seriously affects the normal development of a child and increases their risk of suicide, substance abuse, and psychosocial problems. Early recognition and appropriate treatment are most important." Dr. Carlson also discussed the difficulties of diagnosing BD. "It takes me 3 hours to do an evaluation....This is not something that you just take 30 minutes and get the person in and out. Even when it looks like a kid meets the criteria for [BD], time and effort are necessary before you say, 'I unequivocally know this is bipolar,' "she said. 'Profound' Implications In a study that has recently been accepted for publication, Dr. Carlson and colleagues assessed the implications of parent and teacher concordance on the Child Mania Rating Scale in 911 children between the ages of 5 and 18 years. A total of 7.3% of the participating children were found to have a BD. Of these, 20 had BD type 1, 3 had BD type 2, and 43 had BD not otherwise specified. In addition, when the parent rating was high and the teacher rating low, the diagnosis was usually an anxiety disorder, she said. Although a high parent rating score of manic symptoms (>15) was more associated with a diagnosis of BD than a low score, the child usually ended up having ADHD or oppositional defiant disorder (ODD). "The implications are pretty profound. If you think a kid is having a rapidly cycling disorder and in fact they have an anxiety disorder, you're going to use very different treatments." In a 2010 study (Bipolar Disorders. 2010;12:205-212), Dr. Carlson and colleagues also assessed whether rages are actually manic episodes in 130 children between January 2003 and June 2004. Most were hospitalized for parent-reported rages. "Not surprisingly, community clinicians were more likely to give a diagnosis of bipolar to these kids. But rages are a fairly nonspecific manifestation of a lot of different conditions, such as ODD, autism, posttraumatic stress disorder, schizophrenia, and more." Although the parents often reported manic symptoms, the investigators found that BD usually did not explain the episodes because 84.8% of the children had 1 or fewer rages while in the hospital. She noted that although all of the structured assessments appear useful, "especially in the hands of someone who knows what mania and depression are," the tools are not easily translated "to people who don't understand phenomenology, development, and the breadth of child and adolescent assessment. 9th International Conference on Bipolar Disorder (ICBD): Concurrent Session 3, No. S1. Presented June 11, 2011. "It is not just saying, 'if your parent has bipolar, you must have it too.' It's not a simple, quick, and dirty diagnosis." Boris Birmaher, MD

BIPOLAR DISORDER Patients with Bipolar Disorder typically exhibit what is best described as a “mood cycle”—a pronounced shift in mood and energy from one extreme to another. An example of this would be a child who wakes up with extreme silliness, high energy, and intrusive behavior that persists for several hours and then later in the day becomes sad, depressed, and suicidal with no precipitant for either mood cycle. Bipolar Disorder patients also will exhibit other symptoms of mania during these mood cycling periods. Robert A. Kowatch, MD, PhD: Not all mood swings are bipolar disorder; Current Psychiatry Vol. 10, No. 02 / February 2011: Patients with BD typically exhibit what is best described as a “mood cycle”—a pronounced shift in mood and energy from 1 extreme to another.2 An example of this would be a child who wakes up with extreme silliness, high energy, and intrusive behavior that persists for several hours and then later in the day becomes sad, depressed, and suicidal with no precipitant for either mood cycle. BD patients also will exhibit other symptoms of mania during these mood cycling periods. Robert A. Kowatch, MD, PhD: Not all mood swings are bipolar disorder; Current Psychiatry Vol. 10, No. 02 / February 2011

BD vs. ADHD Sleep (Decreased need vs. DFA then crash) Outbursts (hurricane vs. hand grenade) Elated or expansive mood in BD, not ADHD Hypersexuality (BD>>ADHD) Racing Thoughts (BD>>ADHD) Note – when taking a family history determine how family members were diagnosed with their various conditions. In ADHD the experience is busy thoughts rather than racing thoughts

Attention Deficit/Hyperactivity Disorder Bipolar Mood Disorder Symptoms present at baseline, constant, but may vary briefly based on motivation Episodic with periods of somewhat normal mood Mood outbursts sudden and triggered by frustration & other situations and short-lived (lasting minutes to hours) Moods shift more gradually usually for no apparent reason for days or weeks & may last for weeks to months Strong family history of ADHD Often family history of mood disorder 5-9% of children, 60+% Lifelong, & symptoms appear by age 12 (but age criterion questionable) Rare in children; 1-3% of adults, and 1st episode usually after age 18 Note – when taking a family history determine how family members were diagnosed with their various conditions.

Mick E, Spencer T, Wozniak J, et al. 2005 Mick E, Spencer T, Wozniak J, et al. Heterogeneity of irritability in attention-deficit/hyperactivity disorder subjects with and without mood disorders. Biol Psychiatry. 2005;58(7):576–582 Mick E, Spencer T, Wozniak J, et al. 2005

Autism spectrum disorders (ASD) Autism spectrum disorders include the autistic disorder, Asperger syndrome, and pervasive developmental disorder-not otherwise specified (PDD-NOS). Children with these disorders exhibit impaired social interaction, communication difficulties, and repetitive behaviors or interests. Symptoms that may respond to medication treatment: • Severe irritability (aggression, tantrums, and self-injury) • Hyperactivity and impulsivity • Repetitive interests and behaviors Since the degree of dysfunction varies greatly from patient to patient, multidisplinary management must be individualized to the child’s unique needs.

Reactive Attachment Disorder (RAD) A. A consistent pattern of inhibited, emotionally withdrawn behavior toward adult caregivers, manifested by both of the following: • The child rarely or minimally seeks comfort when distressed. • The child rarely or minimally responds to comfort when distressed. B. A persistent social or emotional disturbance characterized by at least two of the following: • Minimal social and emotional responsiveness to others • Limited positive affect • Episodes of unexplained irritability, sadness, or fearfulness that are evident even during nonthreatening interactions with adult caregivers. DSM-5 Criteria for Reactive Attachment Disorder (RAD) The DSM-5 gives the following criteria for Reactive Attachment Disorder: A. A consistent pattern of inhibited, emotionally withdrawn behavior toward adult caregivers, manifested by both of the following: •The child rarely or minimally seeks comfort when distressed. •The child rarely or minimally responds to comfort when distressed. B. A persistent social or emotional disturbance characterized by at least two of the following: •Minimal social and emotional responsiveness to others •Limited positive affect •Episodes of unexplained irritability, sadness, or fearfulness that are evident even during nonthreatening interactions with adult caregivers. C. The child has experienced a pattern of extremes of insufficient care as evidenced by at least one of the following: •Social neglect or deprivation in the form of persistent lack of having basic emotional needs for comfort, stimulation, and affection met by caring adults •Repeated changes of primary caregivers that limit opportunities to form stable attachments (e.g., frequent changes in foster care) •Rearing in unusual settings that severely limit opportunities to form selective attachments (e.g., institutions with high child to caregiver ratios) D. The care in Criterion C is presumed to be responsible for the disturbed behavior in Criterion A (e.g., the disturbances in Criterion A began following the lack of adequate care in Criterion C). E. The criteria are not met for autism spectrum disorder. F. The disturbance is evident before age 5 years. G. The child has a developmental age of at least nine months. Specify if Persistent: The disorder has been present for more than 12 months. Specify current severity: Reactive Attachment Disorder is specified as severe when a child exhibits all symptoms of the disorder, with each symptom manifesting at relatively high levels.

Diagnosis by Criteria Must meet 3 out of 3 criteria: Possesses two hands Speaks Keeps track of time

(Integrative) Treatment Medication Family Therapy/ Parent Training Spiritual Counseling Environmental Accommodations Behavioral Modification Individual Therapy (CBT) Skill Development Multimodal (Integrative) Treatment

Treatment Strategies Individual Psychotherapy Family therapy Parenting intervention/training Attachment intervention/enhancement Spiritual counseling Psychosocial interventions Psychoeducational interventions Lifestyle interventions Medication

Refer to “The World of the Child” diagram as you address treatment: 1) IEF – Identification and expression of feelings; teach, model and invite child to IEF; make it fun; 2) Modeling following directions with one prompt 3) Addressing sensitivities 4) Address temperament issues 5) Identify and Address Learning Disabilities 6) Provide structure 7) Find points of agreement 8) Collaborative problem-solving as per Ross Greene, PhD 9) School accommodations 10) Acknowledging and enhancing areas of strength 11) Identifying and strengthening areas of weakness gradually and non-judgmentally 12) Addressing attachment issues 13) ETC…………………

Got Questions Ministries: Handling anger is an important life skill. Christian counselors report that 50 percent of people who come in for counseling have problems dealing with anger. Anger can shatter communication and tear apart relationships, and it ruins both the joy and health of many. People tend to justify their anger instead of accepting responsibility for it. Everyone struggles, to varying degrees, with anger. God’s Word contains principles regarding how to handle anger in a godly manner, and how to overcome sinful anger.

Anger must guide us Psalm 7:11 Ephesians 4:26 11 God judgeth the righteous, and God is angry with the wicked every day. (God pronounces a just judgment on behalf of the righteous; he vindicates their character. He continually calls the wicked to repentance by some sign of his judgments.) Ephesians 4:26 26 Be angry and do not sin; do not let the sun go down on your anger, (Biblically, anger is God-given energy intended to help us solve problems.) (This is in keeping with anger aiding survival and motivation).

Self-Control is the Goal James 2:19-20 19 My dear brothers and sisters, take note of this: Everyone should be quick to listen, slow to speak and slow to become angry, 20 because human anger does not produce the righteousness that God desires. Proverbs 19:11 The discretion of a man deferreth his anger; and it is his glory to pass over a transgression. (A person's wisdom yields patience; it is to one's glory to overlook an offense. Sensible people control their temper; they earn respect by overlooking wrongs.)

Being Spiritual Protects People from Depression Those who rated their religious or spiritual beliefs as having high personal importance had one tenth of the risk of other participants for recurrence or new incidence of major depression over 10 years. Supporting religious or spiritual engagement by individuals with such inclinations may offer some protective value. Miller L et al. Religiosity and major depression in adults at high risk: A ten-year prospective study. Am J Psychiatry 2011 Aug 24

Spirituality Shame, low self-esteem Conflict with authority Feeling inferior spiritually Negative interactions, transgressions May think self to not be good enough for God Lack skills for managing spirituality May develop toxic faith – sin management When parents try using shame to try to control child’s behavior it may backfire Cognitive spiritual approach to reframe thinking

How to intervene when the child is in the middle of a rage Maintain safety of child, others, property, self Remain as calm and objective as possible; try to avoid making it worse Think and try to understand why the behavior is happening Try to determine how much control the child has over the behavior Talk with the child after calm Address consequences based on circumstances

When the child is calm If we give a child but one thing, give the child a good self-esteem. Helping the child be able to identify and express feelings appropriately on an ongoing basis. Offer choices: okay to do and what is not okay Playing games (checkers) with the child promotes thinking and decision-making helps the child handle situations better. Control versus influence: I recommend that the parents seek to influence the child to engage good self-control rather than the parents trying to control the child. There are times when the parents must take control of the situation.

Key attitudes/strategies Safety is the top priority Communication: Listening, Understanding, Expressing “It’s not only what you say, it’s how you say it.” First, do no harm Everything must be to help Every thing is an opportunity Learn from everything Find points of agreement Model: whatever you want a child to do, you do it; whatever you don’t want a child to do, you don’t do it. The parent-child relationship is the foundation of the child’s development

The Incredible Years by Carolyn Webster-Stratton A Trouble Shooting Guide for Parents of Children Aged 3-8

Webster-Stratton’s Incredible Years Parent Training Parental intervention (based on Wesbter-Stratton techniques) seems to have a beneficial effect on children with oppositional defiant disorder and may be particularly suitable for children with irritability Webster-Stratton’s parent training series utilizes videotape modeling, role-playing, rehearsal, and weekly homework activities in small groups of 8-14 parents http://incredibleyears.com/ Parental intervention (based on Wesbter-Stratton techniques) seems to have a beneficial effect on children with oppositional defiant disorder and may be particularly suitable for children with irritability, although this needs to be tested further. 18. Scott S, O'Connor TG. An experimental test of differential susceptibility to parenting among emotionally-dysregulated children in a randomized controlled trial for oppositional behavior. J Child Psychol Psychiatry2012;53:1184–93. From Bipolar Disorder and Disruptive Mood Dysregulation in Children and Adolescents: Assessment, Diagnosis and Treatment; by Fernanda Valle Krieger, Argyris Stringaris; Evid Based Ment Health. 2013;16(4):93-94. [In 2014 Mood Disorder Articles]

Examples of Parent Behaviors Collected During Observed Parent-Child Interactions Inappropriate Play Behavior / Parent directed play Competitiveness / Quiz questions Insensitive to child’s signals/cues Intrusion on Child’s Independence Parent assists child with task when unnecessary Parent insists on completing a task his/her way Positive consequences for child’s Inappropriate Behavior Verbal and/or non-verbal attention after inappropriate behavior

Examples of Parent Behaviors Collected During Observed Parent-Child Interactions Commands that are Inappropriate, Ambiguous, Repeated, No-opportunity commands / Stop commands Don’t command without options / Threatening commands Lack of Follow Through / Withdrawing commands Ignoring compliance to commands Lack of praise after compliance Criticism / Negating child’s statements Expressing discontent with child’s performance Physical aggression and/or Verbal aggression

The treatment of a child with impulsive or affective aggression The treatment of a child with impulsive or affective aggression may be successful in one-on-one sessions or in group therapy. Principles include: anxiety management correction of cognitive distortions assertiveness training impulse control strategies stress reduction if applicable, therapy to address trauma. Bates 2006

CONDITIONS MEDICATIONS None Stimulants Antianxiety agents ODD ADHD Anxiety Disorder Depression Bipolar Disorder Disruptive Mood Dysregulation Disorder Psychosis Autism Spectrum Disorders None Stimulants Antianxiety agents Antidepressants Mood Stabilizer α-2A agonists Antipsychotics Any medication option, or combination of medications, may apply to many of the conditions, or combinations of conditions.

Clarification: FDA-Approval - Label FDA approval label dictates what pharmaceutical companies promote regarding a medication. The drug label presents important information about the safety and effective use of the drug Physicians may treat patients with an approved drug for unapproved purposes (“Off-Label” Use) and at doses higher than approved on the label IF based on clinical literature, clinical judgment and clinical experience deemed medically indicated for patients’ welfare Treatment-Emergent Adverse Effects refer to events occurring during treatment study with a medication whether or not medication thought to be responsible.

The treatment of a child with impulsive or affective aggression The treatment of a child with impulsive or affective aggression may be successful in one-on-one sessions or in group therapy. Principles include: anxiety management correction of cognitive distortions assertiveness training impulse control strategies stress reduction if applicable, therapy to address trauma. Bates 2006

Child and Adolescent Bipolar Algorithm 2009 CA Bipolar Algorithm 2009 Current Psychiatry Vol. 8, No. 11 / November 2009 Clinical trials support new algorithm for treating pediatric bipolar mania 4 atypical antipsychotics are proposed as first-line therapy, based on current evidence Robert A. Kowatch, MD, PhD  Professor of psychiatry and pediatrics, Director of psychiatry research, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH  Jeffrey R. Strawn, MD  Clinical fellow, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH  Michael T. Sorter, MD  Associate professor of psychiatry and pediatrics, Director, division of psychiatry, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 

Medications The medication options to control aggression, tantrums and self-injury in children and adolescents with ASDs include atypical antipsychotics, typical antipsychotics, traditional mood stabilizers, and alpha agonists. FDA approval: Two atypical antipsychotics – risperidone and aripiprazole – have FDA approval for pediatric use in ASDs. Risperidone is approved for patients 5-16 years of age to treat irritability associated with ASDs, which typically manifests as tantrums, aggression and self-injurious behaviors. Aripiprazole is approved for the same indication in ages 6-17 years.

MOOD STABILIZERS Divalproate (Depakote, Depakote ER) Lamotrigine (Lamictal, Lamictal XR, Lamictal ODT) Lithium (Eskalith, Lithonate, Lithotabs, Eskalith CR, Lithobid) Oxcarbazepine (Trileptal)

Antipsychotics For Aggression, Psychosis, & Mood Stabilization Coventional Antipsychotics: Haloperidal (Haldol) Chlorpromazine (Thorazine) Atypical Antipsychotics: Aripiprazole (Abilify) Olanzapine (Zyprexa) Quetiapine (Seroquel) Risperidone (Risperdal) Ziprasidone (Geodon)

Antidepressant Medications Selective Serotonin Reuptake Inhibitors (SSRI) Paroxetine (Paxil) Fluoxetine (Prozac) Sertraline (Zoloft) Fluvoxamine (Luvox) Citalopram (Celexa) Escitalopram (Lexapro) Norepinephrine Dopamine Reuptake Inhibitor (NDRI) Bupropion (Wellbutrin, Zyban) Serotonin Antagonist and Reuptake Inhibitor (SARI) Trazodone (Desyrel)

Antidepressant Medications Serotonin Norepinephrine Reuptake Inhibitors (SNRI) Tricyclic Antidepressants Amitriptyline (Elavil) Nortriptyline (Pamelor) Imipramine (Tofranil) Other Venlafaxine (Effexor) Duloxetine (Cymbalta) Tetracyclic: Mirtazepine (Remeron) Monoamine Oxidase Inhibitor (MAO inhibitor) Isocarboxazid (Marplan) Phenelzine (Nardil) Tranylcypromine (Parnate) Emsam

Attention Deficit/Hyperactivity Disorder AD/HD Sympathomimetics & related drugs Methylphenidate (Ritalin, Concerta, Metadate, Daytrana) Amphetamine (Dexedrine, Adderall, Vyvanse) Atomoxetine (Strattera Alpha2-adrenergic receptor agonists Clonidine (Kapvay) Guanfacine (Intuniv) Tricyclics (Imipramine); Bupropion (Wellbutrin) ??? Buspirone (BusPar) and SSRIs

SLL-UP Stop, Look, Listen UP! S = STOP the NEGATIVE L = LOOK for the POSITIVE L = LISTEN (to self, others, environment, situation) U = UNDERSTAND, and then P = PROCEED © Kuhnley 1995

S-A-N-E-R S = SLEEP A = ATTITUDE N = NUTRITION E = EXERCISE R = RELATIONSHIP © Kuhnley 2007

Summary Obtain careful clinical information “in their own words” from multiple sources Mood swings and rage do not equate to Bipolar Disorder (BD) and more likely stem from ADHD, ODD, Anxiety, and/or psychosocial circumstances in the world of the child, BUT must consider BD Treat the patient, not the Diagnosis, though diagnosis guides the treatment, and A multimodal integrative treatment approach must target the causes/impairments and adjust over time as the clinical picture develops

Mark 8 years old

Mark, 8 years old Psychiatric evaluation revealed: Mom reported Mark followed her from room to room, refusing to let her out of his sight. Mark reported that when he was at school he feared his mother had been killed in an auto accident. Mom reported Mark cried every morning before school, often missing the school bus, and forcing mom to drive him to school. Once at school he was irritable and angry. He would go to the office complaining that he was going to vomit. Cheng K, et al. 2005

Mark, 8 years old Diagnosis? On some occasions Mark did vomit, and school personnel called mom to come to school and take him home. On weekends he was better but on Sunday night he complained of headaches and stomachaches. Work-up by pediatric gastroenterologist failed to identify a medical problem. Although Mark was a bright student, he was at risk for failing the third grade and his mom was in danger of losing her job Diagnosis? Cheng K, et al. 2005

Mark, 8 years old Diagnosis—Separation Anxiety Disorder Medication—Sertraline 12.5 mg/day for 2 weeks, then 25 mg/day At school, Mark could leave class if he was physically ill, but only to go to counselor’s office until he recovered Teachers & parents were educated to observe for sertraline’s potential activation Cheng K, et al. 2005

Mark, 8 years old Mark’s symptoms were explained as his body’s response to anxiety and that his worries, stomachaches, and headaches should gradually improve with treatment Parents used a behavioral system to encourage him to sleep in his own bed At 4-week follow-up, Mark and his family were markedly relieved over Mark’s improved anxiety, mood, and function Sertraline-induced behavioral activation - difficulty in falling asleep, hypermotoric behavior, and hypertalkativeness (in association with tremor and blurred vision) Cheng K, et al. 2005

Ashleigh 8 years old

Ashleigh, 8 years old DIAGNOSIS? Several year history of ADHD “mostly” responsive to stimulant medication. History of chronic worry about school, friends, family, safety of herself and her family, and world events. Bouts of decreased concentration and irritability despite stimulant medication. Complaints of headaches, stomachaches, and tiredness. DIAGNOSIS?

Ashleigh, 8 years old Diagnosis: Medications ADHD Generalized Anxiety Disorder Medications Concerta 36 mg q am Zoloft 50 mg q am Anxiety Management Strategies Response—Well-controlled

Ashleigh, 8 years old Follow-up Visit after a year of stable function Mom reports the medication is suddenly no longer working as Ashleigh is recently hyperactive, irritable, distractible, anxious, angry, & acting out behaviorally Review of psychosocial issues with mom fails to reveal any change in stressors or family situation Interview of Ashleigh fails to reveal any stressors Requesting Ashleigh to draw her feelings on the dry erase board revealed ANGER at mom and fear there would not be enough food or enough room when…. Mom had twins!—mom had just learned she was pregnant with twins.

Ashleigh, 8 years old Intervention—assisted mom and Ashleigh in communicating together: Ashleigh enumerated her worries and fears to Mom regarding birth of twins; Mom reaffirmed her love for Ashleigh and assurance of room arrangements and ample food supply; also opportunity to help with twins Outcome—Ashleigh calmed and returned to previous level of good function immediately after session without any adjustment to medication.

MOOD STABILIZERS Divalproate Lamotrigine Lithium Oxcarbazepine (Depakote, Depakote ER) Lamotrigine (Lamictal, Lamictal XR, Lamictal ODT) Lithium (Eskalith, Lithonate, Lithotabs, Eskalith CR, Lithobid) Oxcarbazepine (Trileptal)

References Who Are the Children With Severe Mood Dysregulation, a.k.a. "Rages“? Gabrielle A. Carlson, M.D. , Journal of Child and Adolescent Psychopharmacology, 19.3 (July 2009): p281(8).  Psychiatric Comorbidity, Family Dysfunction, and Social Impairment in Referred Youth With Oppositional Defiant Disorder, Ross W. Greene, Ph.D., Joseph Biederman, M.D., Stephanie Zerwas, B.A., Michael C. Monuteaux, B.A., Jennifer C. Goring, B.A., and Stephen V. Faraone, Ph.D., Am J Psychiatry 159:1214-1224, July 2002 Severe Mood Dysregulation, Irritability, and the Diagnostic Boundaries of Bipolar Disorder in Youths, Ellen Leibenluft, M.D. , Am J Psychiatry 2011; 168:129-142 Oppositional Defiant Disorder, W Douglas Tynan, PhD, emedicine.medscape.com, 2-2-2008 International Handbook of Anger. Chapt 4: Constructing a Neurology of Anger. Michael Potegal and Gerhard Stemmler. 2010

The Demon Child In her own words. Picture from website of Clear View Counseling, 4140 W. Charleston Blvd., Las Vegas, Nevada 89102, (702)254-4883 http://www.clearviewcounseling.com/Anger.php

I remember being on the bed thinking how peaceful it would be to just end it all. I didn’t want to hurt anyone, I just wanted to be happy and safe. I was tired of hiding and trying to find places of peacefulness without being hurt. I had saved $55. I purchased some pills from a guy at school. The confusion and pain were more than I could deal with at the age of 11. I was tired of being scared and tired. At times I was scared of my own self and my temper. I was not like my peers. I was smart and did well in school, but home was a different story.

My temper was a life of its own My temper was a life of its own. I would start out in control of the event knowing what I was doing and what I wanted to get, but then things would become too big and out of control. I would become so worked up that I would want to stop but couldn’t. The anger and the rage would grow and just take over, and soon it would control me. I could hear the adults talking to me but I could not respond.

I could just scream or hit whoever or whatever was in my way I could just scream or hit whoever or whatever was in my way. These fits would last for hours and there was no stopping me. I would feel like I was watching from a distance and it was not me. But it was me and I was one angry child. Then just as quickly my mood would change and I would be the opposite. I would completely withdraw from everyone and I would run and hide where no one was or even knew about. I had a blanket and a flashlight. I would stay there for hours.

But back to the temper. The first few times it was not so bad But back to the temper. The first few times it was not so bad. My mother would say I had that Irish temper but it was more. I would go off without warning or at least they (being my mother) did not see the common factor. My mood would change a great deal depending on who was around me or where I was staying.

I don’t remember getting mad around my grandmother but when I was home and my mother would leave for work (she worked 3rd shift) I would go off--hitting her, my brothers, the walls. Anything I could throw, I would. After the temper I would cycle down going into a fearful mood, I would hide at this point for hours not wanting anyone around me.

In June my oldest brother left for the Air force In June my oldest brother left for the Air force. My reaction was not that of my siblings. I reacted with anger and more destructive behaviors. I slashed the tires of the car, took a hammer to the door, and tore up everything I could find. I refused to talk with my brother on the phone or write him until October of that same year.

My other brother (second oldest) was killed in a car/hunting accident My other brother (second oldest) was killed in a car/hunting accident. Earlier that day I was with him talking about running away and not staying in the same State. We planned to leave, him first, then I was to come to him by December. This all changed. He was buried on my 13th birthday. This destroyed the rest of my world.

I plotted my own death. I was in counseling but I would lie to him daily about how I was feeling, and would put on a happy face. I also began to save my medications or cheeked them daily. By December I was ready. I overdosed once again. This time I took over 70 types of pills and medications ranging from BC to the Prozac. I washed them down with a 5th of Jack Daniels.

This time the State stepped in and took me 118 miles from my home This time the State stepped in and took me 118 miles from my home. This only made things worse. Now I was not manageable by anyone. I would fight with my foster mother physically so they changed my medications, but still I was labeled Bipolar.

My behaviors now affected my school-- the one place I did feel safe and happy. I was suspended six times within 4 months in school for fighting and verbal abuse towards the school staff. The fourth time I hit the teacher with a book. She was sent to the hospital. I was sent to the social services office and from there to a new hospital and a new foster home.

This time I was treated for Bipolar and PTSD (due to my brother’s death) and Anxieties. Medications were added and increased. Nothing changed. On the first day I assaulted the staff. It took five male staff to hold me down and give me a shot to calm me down. After the second shot I went to sleep. When I woke I was in a room with white walls and there was padding on the walls. I was strapped down to a bed in the middle on the room.

At one point I was hospitalized and the doctor was telling me about the rules of the ward and what I would need to do. I did not like him so I punched him. He looked a lot like my father. Anyway I was given a different doctor. Later that day I was in his office and I went off. I remember being in the corner of the room and looking at him. He was crying and I wasn’t. When I asked him why he told me because nobody had taken the time to stop and look at what was wrong with me, that I was tough but I was scared and someone had been hurting me.

For some strange reason I told him about everything--about the abuse and about why I was scared. I didn’t want to be alone with my father--it was really that simple. After that I was no longer Bipolar but a child of abuse and needed help with this. Within a day I was not taking any medications.

Protective Factors VS. Risk Factors HEALTH IMPAIRMENT © Kuhnley 2009

Brain Areas, Neurotransmitters, and Circuits Patients with generalised anxiety disorder (GAD) exhibit increased metabolic rates in several brain regions compared with healthy controls. Hyperactive neurotransmitter circuits between the cortex, thalamus, amygdala and hypothalamus have been implicated in the disorder. Hypofunction of serotonergic neurones arising from the dorsal raphe nucleus and GABAergic neurones that are widely distributed in the brain may result in a lack of inhibitory effect on the putative GAD pathway. Furthermore, overactivity of noradrenergic neurones arising from the locus coeruleus may produce excessive excitation in the brain areas implicated in GAD.

Disruptive Mood Dysregulation Disorder 296. 99 (F34 Disruptive Mood Dysregulation Disorder 296.99 (F34.8) Diagnostic Criteria A. Severe recurrent temper outbursts manifested verbally (e.q., verbal rages) and/or behaviorally (e.q., physical aggression toward people or property) that are grossly out of proportion in intensity or duration to the situation or provocation. B. The temper outbursts are inconsistent with developmental level. C. The temper outbursts occur, on average, three or more times per week. D. The mood between temper outbursts is persistently irritable or angry most of the day, nearly every day, and is observable by others (e.q., parents, teachers, peers). E. Criteria A-D have been present for 12 or more months. Throughout that time, the individual has not had a period lasting 3 or more consecutive months without all of the symptoms in Criteria A-D. F. Criteria A and D are present in at least two of three settings (i.e .. at home, at school, with peers) and are severe in at least one of these. G. The diagnosis should not be made for the first time before age 6 years or after age 18 years. H. By history or observation, the age at onset of Criteria A-E is before 10 years. I. There has never been a distinct period lasting more than 1 day during which the full symptom criteria, except duration, for a manic or hypomanic episode have been met. Note: Developmentally appropriate mood elevation, such as occurs in the context of a highly positive event or its anticipation, should not be considered as a symptom of mania or hypomania. J. The behaviors do not occur exclusively during an episode of major depressive disorder and are not better explained by another mental disorder (e.g., autism spectrum disorder, posttraumatic stress disorder, separation anxiety disorder, persistent depressive disorder [dysthymia]). Note: This diagnosis cannot coexist with oppositional defiant disorder, intermittent explosive disorder, or bipolar disorder, though it can coexist with others, including major depressive disorder, attention-deficit/hyperactivity disorder, conduct disorder, and substance use disorders. Individuals whose symptoms meet criteria for both disruptive mood dysregulation disorder and oppositional defiant disorder should only be given the diagnosis of disruptive mood dysregulation disorder. If an individual has ever experienced a manic or hypomanic episode, the diagnosis of disruptive mood dysregulation disorder should not be assigned. K. The symptoms are not attributable to the physiological effects of a substance or to another medical or neurological condition. DSM-5, APA

Symptom Overlap in GAD and Depression: Diagnostic Dilemma— Symptom Overlap in GAD and Depression: Depression Overlap GAD [Anhedonia] Interest Appetite Esteem Suicide Agitation Dysphoria Sleep problem Fatigue Concentration Restlessness Irritability Worry Urinary frequency Nausea/GI distress Sweating Muscle tension Cardiac symptoms Roy-Byrne P, et al. J Clin Psychiatry. 1997;58(Suppl 3):34.