Early Predictors and Concurrent Correlates of Tonic and Phasic Irritability in Adolescence.

Irritability is a common presenting problem in youth mental health settings that is thought to include two components: tonic (e.g., irritable, touchy mood) and phasic (e.g., temper outbursts), each with unique correlates and outcomes, including later internalizing and externalizing problems, respectively. However, we are unaware of any studies of early predictors of tonic and phasic irritability. We utilized data from a longitudinal study of a community sample of 3-year-old children followed to age 15 (n = 444). We conducted confirmatory factor analysis (CFA) of items from several self-report irritability measures at age 15, including the Affective Reactivity Index, the International Personality Item Pool, the Schedule for Non-Adaptive and Adaptive Personality Youth Version, and the Child Depression Inventory, and examined their early childhood predictors. The CFA identified dimensions consistent with tonic and phasic irritability. Tonic irritability at age 15 was uniquely associated with concurrent internalizing disorders and suicidal behavior while phasic irritability was uniquely associated with concurrent externalizing disorders. When adolescent tonic and phasic irritability were examined together, female sex and parental depressive and substance use disorders at age 3 uniquely predicted adolescent tonic irritability. Additionally, male sex, less parental education, greater laboratory-observed anger and impulsivity, ODD symptoms, higher irritability, and no parental substance use history at age 3 uniquely predicted adolescent phasic irritability. Youth-reported tonic and phasic irritability at age 15 appear to be distinguishable constructs with distinct concurrent correlates and early antecedents. Findings have important implications for research on the etiology of irritability and developing effective treatments.

Irritability across adolescence: Examining longitudinal trajectory, stability, and associations with psychopathology and functioning at age 18.

BACKGROUND: Irritability, marked by diminished frustration tolerance, holds significant implications for youth mental health treatment. Despite prior research on irritability trajectories, understanding of individual differences during adolescence remains limited. This study examines the stability and trajectory of irritability across ages 12-18, investigating associations with psychopathology and functioning at age 18. METHODS: A community sample of families with 3-year-old children (N = 518) was recruited via commercial mailing lists. Irritability was assessed at ages 12, 15, and 18 using the Affective Reactivity Index. Psychopathology at age 18 was evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia, and functioning was assessed through the UCLA Life Stress Interview. Measurement invariance analyses and latent growth curve modeling were conducted within a structural equation modeling (SEM) framework. RESULTS: Configural, metric, and scalar invariance models were supported. Elevated irritability at age 12 predicted adverse outcomes at age 18, including increased psychotropic medication use, mental health treatment, suicidal ideation, self-injury, and psychiatric disorders. Importantly, these associations persisted even after accounting for corresponding variables at age 12. The trajectory of irritability during early adolescence significantly predicted heightened risks for various outcomes at age 18, including suicidal ideation, depression, anxiety, disruptive behavior disorders, and impaired interpersonal functioning. DISCUSSION: Limitations include using only youth-reported data at age 18, limited generalizability from a mostly White, middle-class sample, and insufficient exploration of the broader developmental trajectory of irritability. Nevertheless, the findings emphasize the crucial role of irritability's trajectory in influencing various psychopathological and functional outcomes in late adolescence.

Dorsal visual stream and LIMK1: hemideletion, haplotype, and enduring effects in children with Williams syndrome.

BACKGROUND: Williams syndrome (WS), a rare neurodevelopmental disorder caused by hemizygous deletion of ~ 25 genes from chromosomal band 7q11.23, affords an exceptional opportunity to study associations between a well-delineated genetic abnormality and a well-characterized neurobehavioral profile. Clinically, WS is typified by increased social drive (often termed "hypersociability") and severe visuospatial construction deficits. Previous studies have linked visuospatial problems in WS with alterations in the dorsal visual processing stream. We investigated the impacts of hemideletion and haplotype variation of LIMK1, a gene hemideleted in WS and linked to neuronal maturation and migration, on the structure and function of the dorsal stream, specifically the intraparietal sulcus (IPS), a region known to be altered in adults with WS. METHODS: We tested for IPS structural and functional changes using longitudinal MRI in a developing cohort of children with WS (76 visits from 33 participants, compared to 280 visits from 94 typically developing age- and sex-matched participants) over the age range of 5-22. We also performed MRI studies of 12 individuals with rare, shorter hemideletions at 7q11.23, all of which included LIMK1. Finally, we tested for effects of LIMK1 variation on IPS structure and imputed LIMK1 expression in two independent cohorts of healthy individuals from the general population. RESULTS: IPS structural (p < 10-4 FDR corrected) and functional (p < .05 FDR corrected) anomalies previously reported in adults were confirmed in children with WS, and, consistent with an enduring genetic mechanism, were stable from early childhood into adulthood. In the short hemideletion cohort, IPS deficits similar to those in WS were found, although effect sizes were smaller than those found in WS for both structural and functional findings. Finally, in each of the two general population cohorts stratified by LIMK1 haplotype, IPS gray matter volume (pdiscovery < 0.05 SVC, preplication = 0.0015) and imputed LIMK1 expression (pdiscovery = 10-15, preplication = 10-23) varied according to LIMK1 haplotype. CONCLUSIONS: This work offers insight into neurobiological and genetic mechanisms responsible for the WS phenotype and also more generally provides a striking example of the mechanisms by which genetic variation, acting by means of molecular effects on a neural intermediary, can influence human cognition and, in some cases, lead to neurocognitive disorders.

Offspring irritability: associations with parental psychopathology and personality.

Although there are well-established correlates and outcomes of irritability, there are fewer studies reporting on predictors of the longitudinal course of irritability in youth. The current report examined parent internalizing and externalizing psychopathology and dimensions of personality as predictors of the developmental course of irritability in youth. Offspring irritability was assessed between ages 2 and 10 years using the Irritability Factor from the parent-reported Child Behavior Checklist (N = 570, 53.51% female). Parental psychopathology was assessed with a clinical interview; parents also completed the General Temperament Survey as a measure of personality. Results demonstrated that offspring irritability decreased with age. Offspring irritability was associated with parental depressive and anxiety disorders, higher levels of negative emotionality/neuroticism (NE) and disinhibition, and lower levels of positive emotionality; parental NE and disinhibition remained unique predictors of offspring irritability in a multivariate model. Finally, parental externalizing disorders were associated with more stable trajectories of offspring irritability, whereas offspring of parents without a history of externalizing disorders showed decreasing irritability across time. Findings demonstrate that different aspects of parental personality and psychopathology have differential impacts on levels and course of offspring irritability.

Socioeconomic disadvantage and episodic memory ability in the ABCD sample: Contributions of hippocampal subregion and subfield volumes.

Socioeconomic disadvantage is associated with volumetric differences in stress-sensitive neural structures, including the hippocampus, and deficits in episodic memory. Rodent studies provide evidence that memory deficits arise via stress-related structural differences in hippocampal subdivisions; however, human studies have only provided limited evidence to support this notion. We used a sample of 10,695 9-13-year-old participants from two timepoints of the Adolescent Brain and Cognitive Development (ABCD) Study to assess whether socioeconomic disadvantage relates to episodic memory performance through hippocampal volumes. We explored associations among socioeconomic disadvantage, measured via the Area Deprivation Index (ADI), concurrent subregion (anterior, posterior) and subfield volumes (CA1, CA3, CA4/DG, subiculum), and episodic memory, assessed via the NIH Toolbox Picture Sequence Memory Test at baseline and 2-year follow-up (Time 2). Results showed that higher baseline ADI related to smaller concurrent anterior, CA1, CA4/DG, and subiculum volumes and poorer Time 2 memory performance controlling for baseline memory. Moreover, anterior, CA1, and subiculum volumes mediated the longitudinal association between the ADI and memory. Results suggest that greater socioeconomic disadvantage relates to smaller hippocampal subregion and subfield volumes and less age-related improvement in memory. These findings shed light on the neural mechanisms linking socioeconomic disadvantage and cognitive ability in childhood.

Preschool Irritability Predicts Adolescent Psychopathology and Functional Impairment: A 12-Year Prospective Study.

OBJECTIVE: The long-term clinical and functional outcomes of preschool-age irritability are unknown. This study examined longitudinal associations of preschool irritability with psychiatric disorders and functional impairment assessed in adolescence in a large community sample. METHOD: A total of 453 children were assessed at age 3 and again at ages 12 and/or 15. At age 3, parents were interviewed about their child's irritability, other psychiatric symptoms, and functional impairment with the Preschool Age Psychiatric Assessment (PAPA). In adolescence, both parents and youths were interviewed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime (K-SADS-PL) to assess youth psychopathology and functional impairment; youths also completed the UCLA Life Stress Interview (LSI) to assess different domains of functioning. Lastly, youths and parents completed the Children's Depression Inventory 2 (CDI 2) and the Screen for Child Anxiety Related Disorders (SCARED). RESULTS: Irritability at age 3 predicted internalizing and externalizing disorders in adolescence; parent-reported anxiety and depressive symptoms; and greater functional impairment, including poorer peer functioning, poorer physical health, and antidepressant and educational service use, even after controlling for baseline psychiatric disorders. All longitudinal associations persisted after further adjusting for well-established early life risk markers for psychopathology. CONCLUSION: The findings of this study underscore the clinical significance and predictive power of preschool irritability and provide support for its use in large-scale identification and intervention efforts.