Background Irritability is a common and impairing, transdiagnostic feature of youth psychopathology. Theory distinguishes tonic irritability (persistent irritable mood) from phasic irritability (episodic temper outbursts), yet little is known about how these dimensions co-develop across adolescence into young adulthood and relate to later psychiatric outcomes.Methods Participants were drawn from a longitudinal community cohort assessed at ages 12, 15, 18, and 21 (N = 532 with data at one or more waves). Tonic and phasic irritability were derived from youth-report items spanning multiple measures. We tested the factor structure and longitudinal measurement invariance of tonic and phasic irritability, then modeled co-development using parallel-process latent growth curve models. Sociodemographic factors and parental lifetime psychopathology (assessed at age 9) were examined as predictors of growth factors. Growth factors were used to estimate associations with age-21 psychiatric diagnoses and self-injurious thoughts and behaviors.Results A two-factor model distinguishing tonic and phasic irritability fit better than a one-factor model at each wave, and configural, metric, and scalar invariance were supported from ages 12 to 21. On average, tonic irritability increased modestly whereas phasic irritability declined. Despite divergent mean trajectories, tonic and phasic slopes were positively correlated, indicating coordinated change. Baseline tonic irritability predicted steeper declines in phasic irritability, whereas baseline phasic irritability did not predict change in tonic irritability. Higher tonic intercept and steeper tonic increases were associated with higher odds of depressive and anxiety disorders and suicidal ideation at age 21; tonic intercept also predicted suicidal acts, and tonic change additionally predicted non-suicidal self-injury. In contrast, higher phasic intercept predicted greater odds of disruptive behavior disorders but lower odds of depression, and steeper phasic decline was associated with greater odds of depression.Conclusions Tonic and phasic irritability are separable yet developmentally linked across adolescence into young adulthood and show distinct clinical correlates. Distinguishing persistent mood-based irritability from outburst-based irritability may refine developmental models of risk and intervention targets.
Background Resting‐state functional connectivity (RSFC) studies have consistently identified widespread alterations in the brain's functional network architecture in anorexia nervosa (AN), but it remains unclear whether they are reversible with weight restoration. Furthermore, it is not clear whether there are associations between RSFC and neuroendocrine changes, such as leptin suppression in the underweight state of AN and its increase during short‐term weight restoration. Methods We first analyzed RSFC data cross‐sectionally in young female patients with AN ( n = 117) and healthy control participants ( n = 117) using network‐based statistic (NBS) and graph theory metrics and subsequently explored relationships with plasma leptin as a marker of undernutrition. A subset of patients ( n = 73) was reassessed longitudinally after short‐term weight restoration [mean body mass index (BMI) increase: 28.0%] to test for changes in identified alterations. Results NBS revealed increased RSFC in cingulo‐occipito‐cerebellar circuitry in underweight patients with AN ( p = .0018), which decreased over the inpatient weight restoration interval ( p < .001). This change correlated negatively with plasma leptin concentrations ( p = .042), and plasma leptin appeared to partially mediate the association between BMI increase and RSFC decrease ( p = .039), suggesting a possible region‐specific modulatory effect. Underweight patients with AN also showed higher characteristic path length ( p = .035), indicating reduced integration between brain regions, and higher assortativity ( p = .013), indicating stronger coupling among similarly connected regions. Longitudinally, characteristic path length decreased during weight restoration ( p = .004), whereas findings for assortativity were suggestive of no change. Conclusions The results provide novel longitudinal evidence that functional connectome alterations in AN partially normalize during short‐term weight restoration. Speculatively, taking previous results in long‐term recovered individuals into consideration, higher assortativity might reflect potential vulnerability for AN. Our finding of a tentative association between the normalization of plasma leptin concentrations and RSFC suggests the possibility that leptin may modulate changes in specific patterns of functional connectivity, offering a potential neurobiological target for novel pharmacotherapies.
It is proposed that adverse childhood experiences (ACEs) - potent predictors of mental illness - exert time-dependent effects on neurodevelopment, reflecting periods of heightened neuroplasticity and developmental sensitivity. We systematically reviewed neuroimaging studies examining the role of timing in the association of ACE exposure with brain structure and function across the lifespan. Across 43 studies spanning childhood to adulthood, findings most consistently implicate earlier onset and longer duration of adversity in alterations to limbic and paralimbic regions, including the hippocampus, amygdala, cerebellum and global brain measures. However, evidence for discrete sensitive periods is mixed and varies by brain system, outcome and analytic approach, with no consistent pattern of sensitive periods emerging across adversity types and functional neuroimaging studies remaining comparatively limited. Progress in the field is further constrained by substantial conceptual and methodological heterogeneity, including inconsistent operationalisation of sensitive periods, reliance on retrospective ACE measures and predominantly cross-sectional designs. Moving forward, we argue that advancing the field will require reconceptualising sensitive periods as probabilistic, system-specific and shaped by the nature, timing and chronicity of adversity, rather than as fixed developmental windows. Integrating longitudinal assessment of adversity and neurodevelopment with measures of the neurobiological processes underlying plasticity may help determine whether sensitive periods are better characterised by underlying neuroplasticity than chronological age alone. Improved understanding of these developmental processes may ultimately help inform the timing and targeting of preventive and therapeutic interventions for young people exposed to adversity.
The efficacy–effectiveness gap, the attenuation of benefits as interventions move from controlled trials into routine care, has received substantial focus when scrutinizing psychological interventions but has received less attention in pediatric psychopharmacology. Medication trials evaluate more than molecules: they embed systematic titration, frequent assessment, multi‐informant feedback, and adherence support. This Editorial examines whether differences between trial‐based and routine medication management create a comparable gap. Examples from stimulant treatment in the MTA, antidepressant protocols in TADS and TORDIA, and metabolic surveillance during antipsychotic treatment illustrate how dosing, follow‐up, and safety monitoring may diverge in practice, potentially altering both efficacy and the overall benefit–risk balance. Research should characterize how medications are delivered in routine care and identify which elements of trial‐based management materially improve outcomes. Disseminating evidence‐based pediatric psychopharmacology may require preserving essential medication‐management processes while recognizing constraints faced in practice.
