Nonepisodic Irritability Research Articles

Pediatric Bipolar Disorder Versus Severe Mood Dysregulation: Risk for Manic Episodes on Follow-Up

An important question in pediatric bipolar research is whether marked nonepisodic irritability is a manifestation of bipolar disorder in youth. This study tests the hypothesis that youth with severe mood dysregulation (SMD), a category created for the purpose of studying children presenting with severe nonepisodic irritability, will be significantly less likely to develop (hypo-)manic or mixed episodes over time than will youth with bipolar disorder (BD). Patients with SMD (N = 84) and narrowly defined BD (N = 93) at baseline were followed up in 6-monthly intervals using the relevant K-SADS modules to ascertain (hypo-)manic or mixed episodes. Only one of 84 SMD subjects (1/84 [1.2%]; 95% confidence interval CI = 0.0003 to 0.064) experienced a (hypo-)manic or mixed episode during the study (median follow-up = 28.7 months). The frequency of such episodes was more than 50 times higher in those with narrowly defined BD (58/93 [62.4%]; 95% CI 0.52 to 0.72). These data suggest that, over an approximately 2-year follow-up period, youth with SMD are unlikely to develop (hypo-)manic or mixed episodes.

Practitioner Review: The assessment of bipolar disorder in children and adolescents

An increasing number of youth are being diagnosed with, and treated for, bipolar disorder (BD). Controversy exists about whether youth with non-episodic irritability and symptoms of attention deficit hyperactivity disorder (ADHD) should be considered to have a developmental presentation of mania. A selective review of the literature related to this question, along with recommendations to guide clinical assessment. Data indicate differences between youth with episodic mania and those with non-episodic irritability in longitudinal diagnostic associations, family history, and pathophysiology. In youth with episodic mania, elation and irritability are both common during manic episodes. In diagnosing mania in youth, clinicians should focus on the presence of episodes that consist of a distinct change in mood accompanied by concurrent changes in cognition and behavior. BD should not be diagnosed in the absence of such episodes. In youth with ADHD, symptoms such as distractibility and agitation should be counted as manic symptoms only if they are markedly increased over the youth's baseline symptoms at the same time that there is a distinct change in mood and the occurrence of other associated symptoms of mania. Although different techniques for diagnosing comorbid illnesses have not been compared systematically, it appears most rational to diagnose co-occurring illnesses such as ADHD only if the symptoms of the co-occurring illness are present when the youth is euthymic.

Editorial: Mood irritability – do we need to refine the diagnostic validity of oppositional defiant disorder and paediatric bipolar disorder?

Since Robins and Guze set out criteria for the establishment of diagnostic validity in psychiatric disorders in 1970 – that psychiatric categories should be constructed as distinct and homogeneous entities associated with consistent clinical features, specific biomarkers, a uniform clinical course, a clear delineation from other disorders, and a consistent pattern of familial aggregation – a substantial amount of research has improved the classification of child psychiatric disorders and been incorporated in the two currently established classification systems of ICD-10 and DSM-IV-TR. However, recent advances in neurobiological research in areas such as neuroimaging, molecular genetics, neuropsychology, and neurophysiology have increasingly shown shared biological abnormalities across child psychiatric disorders and substantial heterogeneity within specific diagnostic categories, questioning the diagnostic validity of the current categorical classificatory systems (e.g., Banaschewski et al., 2005; Happé, Ronald, & Plomin, 2006). The first two papers in this issue examine the diagnostic validity of child mental health conditions that share the clinical symptom of mood irritability, paediatric bipolar disorder and oppositional defiant disorder, and will be the focus of my Editorial. Considerable debate regarding appropriate diagnostic criteria has been caused by the concept of paediatric bipolar disorder (PBD), particularly concerning the nosological status of children with nonepisodic, impairing irritability and hyperarousal, or severe mood dysregulation. In this issue, Baroni et al. review the current research on the diagnostic boundaries of bipolar disorder (BD) in youths, in particular the issues of episodicity and irritability, and provide recommendations to guide clinical assessment. Studies comparing children with severe, non-episodic irritability to those with narrow-phenotype bipolar disorder (i.e., discrete episodes of mania with elevated mood) suggest important differences between these phenotypes in clinical correlates, longitudinal course, family history, and psychophysiological mechanisms. The authors advise that, in diagnosing mania in youth, clinicians should stick to DSM criteria and focus on the presence of episodes that consist of a distinct change in mood accompanied by concurrent changes in cognition and behaviour. Thus, the diagnosis of BD should only be made in the presence of identifiable manic or hypomanic episodes. The diagnosis of BD-NOS (not otherwise specified) should be reserved for children with episodes too short to meet DSM-IV-TR duration criteria for mania or hypomania because these children may resemble BD-I and BD-II patients rather than those with nonepisodic, impairing irritability. Lumping both groups together in the BD-NOS category may obscure prominent differences between these two syndromes and constitute a clinically heterogeneous diagnostic category and create a barrier to research clinical practice. The developmental trajectories of oppositional defiant disorder (ODD), one of the most common psychiatric childhood disorders, are not well understood. Although conceptualised as a disruptive behaviour disorder, longitudinal studies indicate an association between childhood ODD and young adult major depressive disorder. Based on cross-sectional data from the epidemiological surveys including representative groups of 18,415 five–sixteen-year-old children, Stringaris and Goodman examine whether the distinction of three dimensions within youth oppositionality would clarify the pattern of associations between oppositionality and other psychopathology in early and adult life. These three dimensions have distinctive external correlates, with irritability being the only predictor of emotional disorders, the hurtful dimension being particularly strongly associated with callousness and aggressive symptoms of later conduct disorder, and the headstrong dimension being most strongly associated with attention deficit hyperactivity disorder and non-aggressive symptoms of conduct disorder. The differential pattern of external associations of the three symptom dimensions raises the possibility that oppositional defiant disorder should rather be understood as a multidimensional category. Further research is needed to investigate the unique and/or common causative factors of each symptom dimension, their underlying (and interacting) neural mechanisms and the related neuropsychological processes, as well as their long-term developmental trajectories to adulthood. Possibly, differential interventions could be developed and delivered to children and adolescents who have oppositional defiant disorder, with corresponding implications for service planning. Further molecular genetic and neurobiological research improving our understanding of the developmental trajectories of functional brain networks underlying symptoms is necessary to refine the diagnostic validity of PBD, ODD and other categorical diagnoses, to clarify the unique and shared pathways of child psychiatric disorders, and to guide the development of new treatment strategies. In that context, prospective longitudinal studies on epidemiological samples are clearly needed, because studies using clinical samples may be biased by referral patterns.

Randomized Double-Blind Placebo-Controlled Trial of Lithium in Youths with Severe Mood Dysregulation

The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal, a syndrome defined as severe mood dysregulation (SMD) by Leibenluft, has been the focus of increasing concern. We conducted the first randomized double-blind, placebo-controlled trial in SMD youth, choosing lithium on the basis of its potential in treating irritability and aggression and neuro-metabolic effects. SMD youths 7-17 years were tapered off their medications. Those who continued to meet SMD criteria after a 2-week, single-blind, placebo run-in were randomized to a 6-week double-blind trial of either lithium (n = 14) or placebo (n = 11). Clinical outcome measures were: (1) Clinical Global Impressions-Improvement (CGI-I) score less than 4 at trial's end and (2) the Positive and Negative Syndrome Scale (PANSS) factor 4 score. Magnetic resonance spectroscopy (MRS) outcome measures were myoinositol (mI), N-acetyl-aspartate (NAA), and combined glutamate/glutamine (GLX), all referenced to creatine (Cr). In all, 45% (n = 20/45) of SMD youths were not randomized due to significant clinical improvement during the placebo run-in. Among randomized patients, there were no significant between-group differences in either clinical or MRS outcome measures. Our study suggests that although lithium may not result in significant clinical or neurometabolic alterations in SMD youths, further SMD treatment trials are warranted given its prevalence.

Autism Spectrum Disorder Scale Scores in Pediatric Mood and Anxiety Disorders

To compare scores on autism spectrum disorder (ASD) symptom scales in healthy youths and youths with mood or anxiety disorders. A total of 352 youths were recruited (107 healthy participants, 88 with an anxiety disorder, 32 with major depressive disorder, 62 with bipolar disorder, and 63 with a mood disorder characterized by severe nonepisodic irritability). Participants received structured psychiatric interviews and parent ratings on at least one of three ASD symptom scales: Children's Communication Checklist, Social Communication Questionnaire, and Social Responsiveness Scale. Relative to healthy youths, youths with mood or anxiety disorders exhibited higher scores on each ASD symptom scale. ASD symptom scale scores also showed an association with impairment severity and attention-deficit/hyperactivity disorder. Among patients with mood disorders but not those with anxiety disorders, consistent, statistically significant associations between diagnosis and ASD symptom scale scores remained even after controlling for potential confounders. Patients with mood disorders exhibit higher scores on ASD symptom scales than healthy youths or youths with anxiety disorders. These data should alert clinicians to the importance of assessing ASD symptoms to identify social reciprocity and communication deficits as possible treatment targets in pediatric mood and anxiety disorders.

Parental Diagnoses in Youth With Narrow Phenotype Bipolar Disorder or Severe Mood Dysregulation

Controversy exists regarding whether nonepisodic irritability and hyperarousal (severe mood dysregulation) is a phenotype of pediatric bipolar disorder. The authors compared axis I diagnoses in parents of children with narrow phenotype bipolar disorder and parents of youth with severe mood dysregulation. Parents of youth with narrow phenotype bipolar disorder (proband N=33, parent N=42) and youth with severe mood dysregulation (proband N=30, parent N=37) were interviewed by clinicians who were blind to the child's diagnostic status using the Diagnostic Interview for Genetic Studies. Compared to parents of youth with severe mood dysregulation, parents of youth with narrow phenotype bipolar disorder were significantly more likely to be diagnosed with bipolar disorder. There were no other diagnostic differences between the two groups. These data suggest that narrow phenotype bipolar disorder may be distinct from severe mood dysregulation in terms of familial aggregation. Additionally, the familiality of narrow phenotype bipolar disorder and adult DSM-IV bipolar disorder is high.

Cognitive Flexibility in Phenotypes of Pediatric Bipolar Disorder

Clinicians and researchers debate whether children with chronic, nonepisodic irritability should receive the diagnosis of bipolar disorder (BD). To address this debate, we evaluated cognitive flexibility, or the ability to adapt to changing contingencies, in three groups of children: narrow-phenotype BD (NP-BD; full-duration manic episodes of elevated/expansive mood; N = 50; 13.1 +/- 2.9 years), severe mood dysregulation (SMD; chronic, nonepisodic irritability; N = 44; 12.2 +/- 2.1 years), and healthy controls (N = 43; 13.6 +/- 2.4 years). Cognitive flexibility is relevant to symptoms of BD involving dysfunctional reward systems (e.g., excessive goal-directed activity and pleasure-seeking in mania; anhedonia in depression). We studied simple and compound reversal stages of the intra-/extradimensional shift task and change task that involves inhibiting a prepotent response and substituting a novel response. On the simple reversal, NP-BD youths were significantly more impaired than both the SMD group and controls. On the compound reversal, NP-BD and SMD youths performed worse than controls. On the change task, NP-BD youths were slower to adapt than SMD subjects. Phenotypic differences in cognitive flexibility may reflect different brain/behavior mechanisms in these two patient populations.

Different Psychophysiological and Behavioral Responses Elicited by Frustration in Pediatric Bipolar Disorder and Severe Mood Dysregulation

Researchers disagree as to whether irritability is a diagnostic indicator for pediatric mania in bipolar disorder. The authors compared the behavioral and psychophysiological correlates of irritability among children with severe mood dysregulation (i.e., nonepisodic irritability and hyperarousal without episodes of euphoric mood) and narrow-phenotype bipolar disorder (i.e., a history of at least one manic or hypomanic episode with euphoric mood) as well as those with no diagnosis (i.e., healthy comparison children). Subjects with severe mood dysregulation (N=21) or narrow-phenotype bipolar disorder (N=35) and comparison subjects (N=26) completed the affective Posner task, an attentional task that manipulated emotional demands and induced frustration. Mood response, behavior (reaction time and accuracy), and brain activity (event-related potentials) were measured. The severe mood dysregulation and narrow-phenotype bipolar disorder groups both reported significantly more arousal than comparison subjects during frustration, but behavioral and psychophysiological performance differed between the patient groups. In the frustration condition, children with narrow-phenotype bipolar disorder had lower P3 amplitude than children with severe mood dysregulation or comparison subjects, reflecting impairments in executive attention. Regardless of emotional context, children with severe mood dysregulation had lower N1 event-related potential amplitude than comparison subjects or children with narrow-phenotype bipolar disorder, reflecting impairments in the initial stages of attention. Post hoc analyses demonstrated that the N1 deficit in children with severe mood dysregulation is associated with oppositional defiant disorder symptom severity. Results indicate that while irritability is an important feature of severe mood dysregulation and narrow-phenotype bipolar disorder, the pathophysiology of irritability may differ among the groups and is influenced by oppositional defiant disorder severity.

Different Psychophysiological and Behavioral Responses Elicited by Frustration in Pediatric Bipolar Disorder and Severe Mood Dysregulation

Objective: Researchers disagree as to whether irritability is a diagnostic indicator for pediatric mania in bipolar disorder. The authors compared the behavioral and psychophysiological correlates of irritability among children with severe mood dysregulation (i.e., nonepisodic irritability and hyperarousal without episodes of euphoric mood) and narrow-phenotype bipolar disorder (i.e., a history of at least one manic or hypomanic episode with euphoric mood) as well as those with no diagnosis (i.e., healthy comparison children). Method: Subjects with severe mood dysregulation (N=21) or narrow-phenotype bipolar disorder (N=35) and comparison subjects (N=26) completed the affective Posner task, an attentional task that manipulated emotional demands and induced frustration. Mood response, behavior (reaction time and accuracy), and brain activity (event-related potentials) were measured. Results: The severe mood dysregulation and narrow-phenotype bipolar disorder groups both reported significantly more arousal than comparison subjects during frustration, but behavioral and psychophysiological performance differed between the patient groups. In the frustration condition, children with narrow-phenotype bipolar disorder had lower P3 amplitude than children with severe mood dysregulation or comparison subjects, reflecting impairments in executive attention. Regardless of emotional context, children with severe mood dysregulation had lower N1 event-related potential amplitude than comparison subjects or children with narrow-phenotype bipolar disorder, reflecting impairments in the initial stages of attention. Post hoc analyses demonstrated that the N1 deficit in children with severe mood dysregulation is associated with oppositional defiant disorder symptom severity. Conclusions: Results indicate that while irritability is an important feature of severe mood dysregulation and narrow-phenotype bipolar disorder, the pathophysiology of irritability may differ among the groups and is influenced by oppositional defiant disorder severity.

Comorbid Anxiety in Phenotypes of Pediatric Bipolar Disorder

There has been limited research on anxiety in pediatric bipolar disorder (BPD). Adult BPD studies suggest comorbid anxiety disorders are common and impact treatment outcome. We explored the association of comorbid anxiety with two phenotypes of pediatric BPD. We studied two groups of children. The first group (BPD; N = 31) represents the "narrow phenotype" of pediatric BPD, meeting stringent DSM-IV criteria for mania, including duration and elevated/expansive mood. The second group (ED; N = 32) exhibited chronic, non-episodic irritability without elation or grandiosity ("broad phenotype"). Both samples demonstrate high prevalence of anxiety (BPD 77.4%; ED 46.9%). In the BPD sample, anxiety predates BPD onset, and those with comorbid anxiety have earlier age of onset of BPD than those without. Children with BPD plus anxiety have more hospitalizations than those without anxiety. ED subjects with and without comorbid anxiety did not differ with respect to onset of ED symptoms or number of hospitalizations. Narrow and broad phenotype BPD children have high rates of comorbid anxiety, although only in the narrow phenotype group is comorbid anxiety associated with greater functional impairment BPD plus comorbid anxiety may represent a particularly severe phenotype of pediatric BPD.

A comparison of long term outcome in first episode schizophrenia patients treated with risperidone or typical antipsychotics

La notion clinique d’irritabilité connaît depuis une dizaine d’années un regain d’intérêt en psychopathologie infanto-juvénile. Et ceci au travers de plusieurs données récentes de la littérature, issues notamment d’études de suivi longitudinal, qui ont clairement souligné son caractère prédictif, à court, moyen et long termes, pour un vaste champ de troubles du comportement et de la régulation des émotions. Cette approche dimensionnelle et transnosographique de l’irritabilité, associée aux dernières données des neurosciences, pourrait faire de l’irritabilité l’équivalent d’un marqueur de type psychopathologique, recouvrant à la fois une composante neurobiologique, cognitive et émotionnelle, dont il importe aujourd’hui de mieux comprendre la séquence développementale et son influence prédictive sur l’étiopathogénie des troubles mentaux de l’enfance à l’âge adulte.For a decade, the concept of irritability has known a renewed interest in infant and child psychopathology. Indeed, longitudinal follow-up studies clearly highlighted their predictive value — in the short, medium and long terms — of a broad field of behavioral disorders and emotion dysregulation. This dimensional and transnosographic approach of irritability, coupled with the latest neuroscience data, points out that irritability could be the equivalent of a psychopathological marker, covering both a neurobiological, cognitive and emotional component. It is a major challenge today to better understand the developmental sequence of severe chronic irritability and its predictive influence on the etiology of mental disorders from childhood to adulthood.We briefly review here the latest current data on this topic.The important point is that chronic and non-episodic irritability in children, associated with strong emotional sensitivity to negative events and frequent access of anger, could have a predictive value for progression to anxiety disorder or severe mood disorder but not to bipolar disorder as it was believed until now. The risk of developing a bipolar disorder would be more frequently correlated with the notion of transient and episodic irritability in a context of previous family history of bipolar disorder.Further studies are expected to narrow the discriminative validity of this notion of severe irritability and confirm or not its relevance as a major clinical criterion of Severe Mood Disorders in children and adolescents introduced in the last version of DSM (DSM-5).