Novel insights into irritability: the relationship between subjective experience, age and mood

Background The relationship between irritability as a subjective experience and the behavioural indicators typically used to measure the construct are not known. Its links to mood, and contextual relationships, vary with age and are yet to be thoroughly examined. Aims First, to interrogate the relationship between the subjective experience of irritability and mood, and that with its behavioural indicators. Second, to determine how these relationships vary with age and over time. Method This study examined data from a previous clinical trial of adolescents and young adults (N = 82) with bipolar disorder, who received a psychological intervention over 18 months. Participants completed a battery of questionnaires, which included assessments of irritability. Analyses of covariance were conducted to examine the interaction between mood symptoms, subjective measures of irritability, behavioural measures of irritability and age over time. Results Subjective irritability scores differed significantly over time when controlling for manic, but not depressive, symptom scores. Further, subjective irritability significantly differed when controlling for behavioural measures of irritability (temper outbursts and argumentativeness). There were significant interactions between scores of depressive symptoms, temper outbursts and subjective irritability with age, wherein younger participants showed no correlation between depressive symptoms and temper outbursts. In addition, younger participants showed lower correlations between subjective irritability and both depressive and temper outburst scores, than older participants. Conclusions Subjective irritability is linked to mood morbidity and behavioural outbursts, and these relationships are contingent on age. Our novel findings suggest that subjective irritability should be assessed in greater detail in patients with mood disorders.

Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. However, a limiting factor for treatment studies in PWS is the lack of consensus in the field regarding how to best define and measure the complex and interrelated behavioral features of this syndrome. The International PWS Clinical Trials Consortium (PWS-CTC, www.pwsctc.org) includes expert PWS scientists, clinicians, and patient advocacy organization representatives focused on facilitating clinical trials in this rare disease. To address the above gap in the field, members of the PWS-CTC “Behavior Outcomes Working Group” sought to develop a unified understanding of the key behavioral features in PWS and build a consensus regarding their definition and description. The primary focus of this paper is to present consensus definitions and descriptions of key phenotypic PWS behaviors including hyperphagia, temper outbursts, anxiety, obsessive–compulsive behaviors, rigidity, and social cognition deficits. Patient vignettes are provided to illustrate the interrelatedness and impact of these behaviors. We also review some available assessment tools as well as new instruments in development which may be useful in measuring these behavioral features in PWS.

Chronically irritable mood with frequent temper outbursts

Disruptive mood dysregulation disorder (DMDD) is a new diagnostic addition to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The core feature of the disorder is chronic, severe, and persistent irritability that manifests as frequent temper outbursts that are inconsistent with the patient’s developmental level. The temper outbursts can be verbal or behavioral including physical aggression or property destruction. Between outbursts, the child remains persistently irritable or angry for most of the day, nearly every day. These symptoms persist across time and settings and are easily observable by others. Psychotherapeutic interventions including parent training and individual psychotherapy are critical components of a comprehensive treatment plan. Since DMDD is a new diagnosis, there are no published randomized controlled medication trials. The use of selective serotonin reuptake inhibitors (SSRIs) or second-generation antipsychotics may be considered for decreasing irritability.

Hypomethylation of Monoamine Oxidase A promoter/exon 1 region is associated with temper outbursts in Prader-Willi syndrome

Background: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by the absence of paternally expressed and maternally imprinted genes on chromosome 15q 11.2-13. It is associated with a certain behavioural phenotype with repetitive and ritualistic behaviours, skin-picking and temper outbursts. Temper outbursts are characterized by verbal and physical aggression with screaming, destroying property, and/or physical aggression towards others. They drastically effect the quality of life of the individuals as well as the relatives and caregivers. Recent studies show a promising therapeutic effect of serotonin reuptake inhibitors like sertraline on frequency and intensity of outbursts. Monoamine oxidase A (MAOA) (X p11.23) plays a crucial role in the metabolism of monoamines such as serotonin, norepinephrine, and dopamine. Dysregulation in methylation of the CpG island spanning the promoter region and exon 1 of MAOA is implicated in impulsive and aggressive behaviour. Methods: In the present study, methylation rates of CpG dinucleotides in the MAOA promoter and exon 1 region were determined from DNA derived from whole blood samples of PWS patients (n=32) and controls (n=14) matched for age, sex and BMI via bisulfite sequencing. PWS patients were grouped into those showing temper outbursts, and those who do not. Results: Overall, PWS patients show a significant lower methylation rate at the promoter/exon 1 region than healthy controls in both sexes. Furthermore, PWS patients, male as well female with temper outbursts show a significant lower methylation rate than those without temper outbursts (p<0.001 and p=0.006) Conclusion: The MAOA promoter/exon 1 region methylation seems to be dysregulated in PWS patients in sense of a hypomethylation, especially in those suffering from temper outbursts. As MAOA is involved in the metabolism of serotonin, we conclude that this dysregulation plays a crucial role in the pathophysiology of temper outbursts in PWS. Furthermore, our findings suggest, that dysregulation of certain genes outside the PWS locus contribute to the behavioural phenotype of PWS.