Identifying Novel Types of Irritability Using a Developmental Genetic Approach.

OBJECTIVE: Irritability, which is strongly associated with impairment and negative outcomes, is a common reason for referral to mental health services but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. The authors used a developmental approach to test the hypothesis that there are several forms of irritability, including a "neurodevelopmental/ADHD-like" type, with onset in childhood, and a "depression/mood" type, with onset in adolescence. METHODS: Data were analyzed from the Avon Longitudinal Study of Parents and Children, a prospective U.K. population-based cohort. Irritability trajectory classes were estimated for 7,924 individuals with data at multiple time points across childhood and adolescence (four possible time points from approximately ages 7 to 15). Psychiatric diagnoses were assessed at approximately ages 7 and 15. Psychiatric genetic risk was indexed by polygenic risk scores (PRSs) for attention deficit hyperactivity disorder (ADHD) and depression, derived using large genome-wide association study results. RESULTS: Five irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), late-childhood limited (5.2%), and high-persistent (2.4%). The early-onset high-persistent trajectory was associated with male preponderance, childhood ADHD (odds ratio=108.64, 95% CI=57.45-204.41), and ADHD PRS (odds ratio=1.31, 95% CI=1.09-1.58). The adolescent-onset increasing trajectory was associated with female preponderance, adolescent depression (odds ratio=5.14, 95% CI=2.47-10.73), and depression PRS (odds ratio=1.20, 95% CI=1.05-1.38). Both the early-onset high-persistent and adolescent-onset increasing trajectory classes were associated with adolescent depression diagnosis and ADHD PRS. CONCLUSIONS: The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability may be more neurodevelopmental/ADHD-like and later-onset irritability more depression/mood-like. These findings have implications for treatment as well as nosology.

The association between mixed symptoms, irritability and functioning measured using smartphones in bipolar disorder.

OBJECTIVE: To (i) validate patient-evaluated mixed symptoms and irritability measured using smartphones against clinical evaluations; (ii) investigate associations between mixed symptoms and irritability with stress, quality of life and functioning, respectively, in patients with bipolar disorder. METHODS: A total of 84 patients with bipolar disorder used a smartphone-based system for daily evaluation of mixed symptoms and irritability for nine months. Clinically evaluated symptoms, stress, quality of life and clinically rated functioning were collected multiple times during follow-up. RESULTS: Patients presented mild affective symptoms. Patient-reported mixed symptoms and irritability correlated with clinical evaluations. In analyses including confounding factors there was a statistically significant association between both mixed symptoms and irritability and stress (P < 0.0001) and between irritability and both quality of life and functioning (P < 0.0001) respectively. There was no association between mixed mood and both quality of life and functioning. CONCLUSION: Mixed symptoms and irritability can be validly self-reported using smartphones in patients with bipolar disorder. Mixed symptoms and irritability are associated with increased stress even during full or partial remission. Irritability is associated with decreased quality of life and functioning. The findings emphasize the clinical importance of identifying inter-episodic symptoms including irritability pointing towards smartphones as a valid tool.

Pathways of Association Between Childhood Irritability and Adolescent Suicidality.

OBJECTIVE: Childhood irritability predicts suicidal ideation/attempt (suicidality), but it is unclear whether irritability is an independent and direct risk factor for suicidality or a marker of intermediate mental health symptoms associated with suicidality. This study aimed to identify developmental patterns of childhood irritability and to test whether childhood irritability is directly associated with suicidality or indirectly associated with intermediate mental health symptoms. METHOD: One thousand three hundred ninety-three participants from the Québec Longitudinal Study of Child Development were followed from birth to 17 years. Teachers assessed irritability yearly (at 6-12 years) and children self-reported intermediate mental health symptoms (depression, anxiety, disruptiveness, and hyperactivity-impulsivity; at 13 years) and suicidality (at 15 and 17 years). RESULTS: Four irritability trajectories were identified: low (74.7%), rising (13.0%), declining (7.4%), and persistent (5.0%). Children following a rising irritability trajectory (versus a low trajectory) were at higher suicidality risk. A large proportion of this association was direct (odds ratio 2.11, 95% CI 1.30-3.43) and a small proportion was indirect by depressive symptoms (accounting for 23% of the association; odds ratio 1.17, 95% CI 1.03-1.34). Children on a persistent irritability trajectory (versus a low trajectory) were at higher risk of suicidality and this association was uniquely indirect by depressive symptoms (accounting for 73% of the association; odds ratio 1.51, 95% CI 1.16-1.97). The declining trajectory was not related to suicidality; no association with anxiety, disruptiveness, and hyperactivity-impulsivity was found. CONCLUSION: Rising irritability across childhood represents a direct risk for suicidality. Persistent irritability appears to be a distal marker of suicidality acting through more proximal depressive symptoms.

Characteristics of depressive and bipolar disorder patients with mixed features.

OBJECTIVE: To assess differences between subjects with vs. without mixed features in major affective disorders. METHODS: In 3099 out-patient subjects with DSM-5 major depressive disorder (MDD, n = 1921) or bipolar disorders (BD, n = 1178), we compared those with (Mx) vs. without (Non-Mx) mixed features (agitated-irritable depression or dysphoric [hypo]mania) in an index episode. RESULTS: Prevalence of Mx averaged 21.9% [CI: 20.5-23.4] overall, ranking: BD-II > BD-I > MDD, and in BD depression ≥ [hypo]mania > MDD. Mx subjects were significantly more likely than Non-Mx cases to (i) have other mixed episodes, (ii) have higher irritable and agitated ratings, (iii) have more substance abuse, (iv) switch into mixed episodes, (v) have more suicide attempts and higher suicidal ratings, (vi) change diagnosis from depression to BD, (vii) have higher hypomania scores when depressed or depression scores when [hypo]manic, (viii) be unmarried or separated with fewer children and siblings, (ix) be diagnosed more with BD than MDD, (x) be unemployed, (xi) have BD, suicide and divorce among first-degree relatives, (xii) be female, (xiii) be younger at illness-onset. Both BD and MDD Mx subjects also received antidepressants less, but antipsychotics and mood-stabilizers more, alone and in combination with antidepressants. CONCLUSIONS: Mood disorder subjects with agitated-irritable depression or dysphoric [hypo]mania differed from those without such mixed features, including having a less favorable clinical course and repeated mixed episodes. They may represent a distinct and prevalent, syndromal clinical subtype with prognostic and therapeutic significance.

Affective temperaments in anorexia nervosa: The relevance of depressive and anxious traits.

BACKGROUND: Affective temperaments have been so far understudied in anorexia nervosa (AN) despite the relevance of personality and both affective and anxious comorbidity with regard to vulnerability, course, and outcome of this deadly disorder. METHODS: Ninety-eight female inpatients diagnosed with AN and 131 healthy controls (HCs) were enrolled in this study and completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) in addition to assessments of eating psychopathology, depression, and anxiety. RESULTS: AN patients and HCs differed in all affective temperaments. The diagnostic subtypes of AN differed as well with binge-purging individuals being more cyclothymic and anxious than those with restricting-type AN. TEMPS-A scores correlated with body mass index and eating psychopathology but not with duration of illness. Concerning comorbidity, grater scores on the depressive and lower scores on the hyperthymic temperaments were found in depressed patients. Those who had either an anxious or irritable temperament were significantly more diagnosed with an anxious disorder than those who did not show this temperament. When logistic regression was performed, high depressive/low hyperthymic and high irritable/anxious traits resulted to be associated with depressive and anxious comorbidity, respectively, independently of confounding factors. LIMITATIONS: Cross-sectional design, some patients on medications, few baseline clinical differences between diagnostic subtypes, no other personality assessments. CONCLUSIONS: An affective continuum strongly associated with mood and anxious comorbidity emerged in AN. Such an evaluation could have several research and clinical implications given the need of improving treatment individualization and early interventions for such a complex disorder.

Irritability in child and adolescent psychopathology: An integrative review for ICD-11.

In preparation for the World Health Organization's development of the Eleventh Revision of the International Classification of Diseases and Related Health Problems (ICD-11) chapter on Mental and Behavioral Disorders, this article reviews the literature pertaining to severe irritability in child and adolescent psychopathology. First, research on severe mood dysregulation suggests that youth with irritability and temper outbursts, among other features of hyperactivity and arousal, demonstrate cross-sectional correlates and developmental outcomes that distinguish them from youth with bipolar disorder. Second, other evidence points to an irritable dimension of Oppositional Defiant Disorder symptomatology, which is uniquely associated with concurrent and subsequent internalizing problems. In contrast to the Diagnostic and Statistical Manual of Mental Disorders' (5th ed.) Disruptive Mood Dysregulation Disorder, our review of the literature supports a different solution: a subtype, Oppositional Defiant Disorder with chronic irritability/anger (proposal included in Appendix). This solution is more consistent with the available evidence and is a better fit with global public health considerations such as harm/benefit potential, clinical utility, and cross-cultural applicability. Implications for assessment, treatment, and research are discussed.

Irritability in Childhood and Adolescence.

Irritability is common among children 5 and younger and is defined as a marked predisposition to anger. Irritability in childhood is associated with later psychopathology, suicide, and financial instability. Its persistence through later childhood may be associated with mood, anxiety, and substance use disorders. Assessment of irritability and psychiatric nursing implications are discussed. [Journal of Psychosocial Nursing and Mental Health Services, 54(12), 28-31.].

Separating the domains of oppositional behavior: comparing latent models of the conners' oppositional subscale.

OBJECTIVE: Although oppositional defiant disorder (ODD) is usually considered the mildest of the disruptive behavior disorders, it is a key factor in predicting young adult anxiety and depression and is distinguishable from normal childhood behavior. In an effort to understand possible subsets of oppositional defiant behavior (ODB) that may differentially predict outcome, we used latent class analysis of mother report on the Conners' Parent Rating Scales Revised Short Forms (CPRS-R:S). METHOD: Data were obtained from mother report for Dutch twins (7 years old, n = 7,597; 10 years old, n = 6,548; and 12 years old, n = 5,717) from the Netherlands Twin Registry. Samples partially overlapped at ages 7 and 10 years (19% overlapping) and at ages 10 and 12 years (30% overlapping), but not at ages 7 and 12 years. Oppositional defiant behavior was measured using the six-item Oppositional subscale of the CPRS-R:S. Multilevel LCA with robust standard error estimates was performed using the Latent Gold program to control for twin-twin dependence in the data. Class assignment across ages was determined and an estimate of heritability for each class was calculated. Comparisons with maternal report Child Behavior Checklist (CBCL) scores were examined using linear mixed models at each age, corrected for multiple comparisons. RESULTS: The LCA identified an optimal solution of four classes across age groups. Class 1 was associated with no or low symptom endorsement (69-75% of the children); class 2 was characterized by defiance (11-12%); class 3 was characterized by irritability (9-11%); and class 4 was associated with elevated scores on all symptoms (5-8%). Odds ratios for twins being in the same class at each successive age point were higher within classes across ages than between classes. Heritability within the two "intermediate" classes was nearly as high as for the class with all symptoms, except for boys at age 12. Children in the Irritable class were more likely to have mood symptoms on the CBCL scales than children in the Defiant class but demonstrated similar scores on aggression and externalizing scales. Children in the All Symptoms class were higher in both internalizing and externalizing scales and subscales. CONCLUSIONS: The LCA indicates four distinct latent classes of oppositional defiant behavior, in which the distinguishing feature between the two intermediate classes (classes 2 and 3) is the level of irritability and defiance. Implications for the longitudinal course of these symptoms, association with other disorders, and genetics are discussed.

A cluster analysis-derived classification of psychological distress and illness behavior in the medically ill.

BACKGROUND: The classification of psychological distress and illness behavior in the setting of medical disease is still controversial. Current psychiatric nosology does not seem to cover the spectrum of disturbances. The aim of this investigation was to assess whether the joint use of DSM-IV categories and the Diagnostic Criteria for Psychosomatic Research (DCPR), that provide identification of syndromes related to somatization, abnormal illness behavior, irritable mood, type A behavior, demoralization and alexithymia, could yield subtyping of psychosocial variables in the medically ill. METHOD: A cross-sectional assessment using both DSM-IV and the DCPR was conducted in eight medical centers in the Italian Health System. Data were submitted to cluster analysis. Participants were consecutive medical out-patients and in-patients for whom a psychiatric consultation was requested. A total of 1700 subjects met eligibility criteria and 1560 agreed to participate. RESULTS: Three clusters were identified: non-specific psychological distress, irritability and affective disturbances with somatization. CONCLUSIONS: Two-step cluster analysis revealed clusters that were found to occur across clinical settings. The findings indicate the need of expanding clinical assessment in the medically ill to include the various manifestations of somatization, illness behavior and subclinical distress encompassed by the DCPR.

The Irritability Questionnaire: a new scale for the measurement of irritability.

Irritability is an important symptom in patients with neuropsychiatric disorders. It is a major source of distress to patients and their carers and can lead to social and family dysfunction. Despite this, there has been little systematic research on irritability in psychiatry. The development of an instrument that captures the various components of irritability is a prerequisite to more detailed research in this area. The aim of this study was to design a scale to measure irritable mood and to explore its nature and subtypes. Following a review of the literature and examination of current theories in affective neuroscience, a new self-rating questionnaire was developed covering a range of subjective experiences, judgements and behaviours deemed to encompass the components of irritability. The items were rated along intensity and frequency dimensions. The questionnaire was administered to patients with affective disorders (n=22), Huntington's disease (n=23), Alzheimer's disease (n=19) and a control group (n=46). The new questionnaire shows good reliability and validity. Preliminary differences in irritability were identified between the diagnostic groups.

Paranoia and dysphoria: historical developments, current concepts.

Regarding diagnostic criteria for paranoia (delusional disorder) today psychiatry usually refers to Kraepelin, suggesting that this diagnostic category has existed more or less unchanged since the end of the 19th century. But, reviewing German literature on this topic, one can find a lively discussion with regard to definition, development and course. In this context, the position of affective symptomatology - especially dysphoria with its various meanings - is of major interest. This paper aims at clarifying some definitory questions and at recalling the 'old' paranoia dispute which is worth rediscovering as a stimulation for modern classification and clinical practice.

Dysphoria from a transnosological perspective.

The objective of our psychopathological analyses is to shed light on the position of irritable mood (dysphoria) in psychiatric diagnostics and nosology. In today's most commonly applied classification systems, the ICD-10 and the DSM-IV, dysphoria is mentioned mostly in the context of diagnostic criteria of personality and affective disorders. Other authors have emphasized the importance of dysphoric states in organic psychoses and delusional disorders. Summarizing the various publications on the nosological position, dysphoria is a nosological nonspecific syndrome which may occur in the course of all psychiatric disorders and illnesses. According to the results of our psychopathological analyses, the pathogenesis of dysphoria has to be considered as a multidimensional circular process in which various mental, physical and social factors act as predisposing, triggering and disorder-maintaining factors. Stressors induced by particular experiences and perceptions and by impaired health may lead to a dysphoric state if adequate coping mechanisms are missing. Dysphoria itself usually leads to a deterioration in the mental and physical state of the patient, and shows a clear impact on the patient's social network. The reactions of people close to the patient combined with the impaired mental and physical conditions of the patient cause the circle to restart. As contemporary diagnostic entities do not refer to pathogenesis, classical categorical diagnostics cannot provide the basis for effective pathogenesis-oriented therapy. A change of paradigm in diagnostics from a categorical to a dimensional approach thus becomes necessary. Following a dimensional diagnostic approach based on a dynamic model of vulnerability, a precise differential diagnosis of the complex constellation of conditions and their interactions becomes necessary in order to develop effective treatment strategies. Disorder-maintaining factors determine the treatment of the acute symptomatology, whereas predisposing and triggering factors serve as the basis for the prophylactic treatment.

The semi-structured affective temperament interview (TEMPS-I). Reliability and psychometric properties in 1010 14-26-year old students.

BACKGROUND: The purpose of this study was to evaluate the reliability and psychometric properties of the Semistructured Affective Temperament Interview, and determine cut-offs for each temperament. METHOD: 1010 Italian students aged between 14 and 26 were evaluated by means of the Akiskal and Mallya criteria in a Semistructured Interview for depressive, cyclothymic, hyperthymic, and irritable temperaments. RESULTS: This instrument has very good reliability and internal consistency. The percentage of subjects with a z-score higher than the second positive standard deviation ( + 2 SD) on the scales of depressive and cyclothymic temperaments are 3.6% and 6.3% (reaching scores of 7/7 and 9/10), respectively. Hyperthymic traits, on the other hand, are widespread in our sample: most subjects are included within the second positive standard deviation ( + 2 SD), and 8.2% of these reach a 7/7 score; therefore, the problem of defining a cut-off for this temperament is still open. By contrast, the irritable temperament is rare, conforming to a non-gaussian distribution, with 2.2% of cases above the second positive standard deviation ( + 2 SD). LIMITATION: The data are based on subject report without collateral information and external validation. CONCLUSION: This study contributes to more accurate definition of cut-offs for individual temperament scales. The standardization of the interview thus makes it possible to compare three out of four temperamental scales, showing the dominant temperamental characteristics for each subject. Prospective studies are needed to demonstrate the stability of these traits over time.

Making it without losing it: Type A, achievement motivation, and scientific attainment revisited.

In a study by Matthews, Helmreich, Beane, and Lucker (1980), responses by academic psychologists to the Jenkins Activity Survey for Health Prediction (JAS), a measure of the Type A construct, were found to be significantly, positively correlated with two measures of attainment, citations by others to published work and number of publications. In the present study, JAS responses from the Matthews et al. sample were subjected to a factor analysis with oblique rotation and two new subscales were developed on the basis of this analysis. The first, Achievement Strivings (AS) was found to be significantly correlated with both the publication and citation measures. The second scale, Impatience and Irritability (I/I), was uncorrelated with the achievement criteria. Data from other samples indicate that I/I is related to a number of health symptoms. The results suggest that the current formulation of the Type A construct may contain two components, one associated with positive achievement and the other with poor health.