Systematic Review and Meta-analysis: Task-based fMRI Studies in Youths With Irritability

Lee, Ka Shu; Hagan, Cheyanne; Hughes, Mina; Cotter, Grace; Freud, Eva McAdam; Kircanski, Katharina; Leibenluft, Ellen; Brotman, Melissa A.; Tseng, Wan‐Ling

doi:10.1016/j.jaac.2022.05.014

Cited by 23 publications

(30 citation statements)

References 81 publications

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“…Both the double-runway and operant conditioning chamber methods, however, require weeks of training (14)(15)(16). Long training periods are unsuited to study irritability-like behavior in mice, as DMDD is a disorder diagnosed in children aged [6][7][8][9][10][11][12][13][14][15][16][17][18], which corresponds to only 3-6 weeks of ages in mice (17). The short developmental period of mice restrains the duration of the behavioral paradigm.…”

Section: Introductionmentioning

confidence: 99%

“…Human studies of brain-based mechanisms of irritability are limited and have yielded mixed results (18). Preliminary studies find that high levels of irritability following frustration in patients with DMDD correspond with increased frontal-striatal activation in the anterior cingulate cortex, dorsolateral prefrontal cortex, caudate, amygdala, and parietal cortex (9, 19, 20).…”

Section: Introductionmentioning

confidence: 99%

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A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration

Naik

Munyeshyaka

et al. 2023

Preprint

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BackgroundIrritability, which can be defined as proneness to anger that can reach a pathological extent, is one of the most common reasons youth present for psychiatric evaluation and care. Aberrant responses to frustrative non-reward (FNR, the response to omission of an expected reward) are central to the pathophysiology of irritability. FNR is a cross-species RDoC construct. The development of preclinical FNR models could advance mechanistic studies of the important, and relatively understudied, clinical phenomenon of irritability.MethodsWe used FNR, a translational construct across species, as a conceptual framework for a novel behavioral paradigm (Alternate Poking Reward Omission, APRO) in mice. After APRO, mice were examined with a battery of behavioral tests to determine the effects of frustration. Also, whole brain imaging of c-Fos expression was used to identify brain regions activated by FNR.ResultsMice, regardless of sex, increased locomotion, and aggression towards conspecifics after APRO. There was no change in anxiety-like, depression-like, or non-aggressive social behaviors. APRO causes activation of 13 regions in the prelimbic, ACC, hippocampus, dorsal thalamus, cuneiform nucleus, pons, and pallidum areas, and shifts the brain network towards a more global processing mode.ConclusionOur novel FNR paradigm produces a frustration effect and alters brain processing in ways resembling the symptoms and brain network reconfiguration observed in youth with severe irritability. The novel behavioral paradigm and brain regions identified to be selectively activated by it lay the groundwork for further mechanistic studies of frustration and irritability in rodents.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration

Naik

Munyeshyaka

et al. 2023

Preprint

Self Cite

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“…As mentioned, the examination of the neural correlates of irritability have primarily focused on child and adolescent samples (Lee et al, 2022;Perlman et al, 2015). A meta-analysis of the existing studies of the neural correlates found that across 11 studies focusing on structural MRI (Lee et al, 2022), there was little consensus in terms of regions. Five of the studies identified reduced volume across broad regions of the prefrontal cortex and inferior frontal gyrus and three studies reported reduced insular volume.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, to advance RDoC's goal of understanding psychopathology across a normal:abnormal spectrum in terms of mechanistic pathways, recent studies have focused on placing irritability as a transdiagnostic indicator of psychopathology within a neurodevelopmental context and examining its neurobiological correlates (Klein et al., 2021; Nielsen et al., 2021; Wakschlag et al., 2018). While studies have identified both structural and functional correlates of irritability, these studies have primarily focused on irritability in childhood and adolescence (Lee et al., 2022; Perlman et al., 2015). However, the increasing evidence that atypical irritability can be identified behaviorally in the first years of life, aligning with the RDoC framework, now enables interrogation of corollary neural antecedents of early irritability (Finlay‐Jones et al., 2023; Krogh‐Jespersen et al., 2022; Liu et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

“…As mentioned, the examination of the neural correlates of irritability have primarily focused on child and adolescent samples (Lee et al., 2022; Perlman et al., 2015). A meta‐analysis of the existing studies of the neural correlates found that across 11 studies focusing on structural MRI (Lee et al., 2022), there was little consensus in terms of regions. Five of the studies identified reduced volume across broad regions of the prefrontal cortex and inferior frontal gyrus and three studies reported reduced insular volume.…”

Section: Introductionmentioning

confidence: 99%

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Caudate volume is prospectively associated with irritability in toddlerhood: A preliminary investigation

Dufford,

MacNeill,

Zhang

et al. 2024

Developmental Psychobiology

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Irritability refers to the dispositional tendency to respond with anger and frustration to environmental challenges or limits, with both mood and behavioral elements. The dimensional spectrum of irritability is an RDoC‐informed transdiagnostic marker of psychopathology risk, specifically for the common and modifiable internalizing and externalizing disorders. Despite substantial interest in this robust developmentally based transdiagnostic indicator of psychopathology risk, its early brain markers are understudied. Here, we leveraged high‐quality, longitudinal behavioral phenotyping of irritability within an imaging substudy (n = 31) of toddlers, from the When to Worry (W2W) study. We examined prospective associations between volume in three subcortical regions implicated in irritability (the caudate, putamen, and amygdala) around the infants’ first birthday (Baseline) and the dimensional spectrum of observed irritability using the Disruptive Behavior Diagnostic Observation Schedule (DB‐DOS) around toddlers’ second birthday (Follow‐up). Both left (q = .04, FDR corrected) and right caudate volumes (q = .04, FDR corrected) at Baseline were negatively associated with observed irritability at Follow‐up. We did not find support for associations between putamen and amygdala volumes at Baseline and observed irritability at Follow‐up. These findings identify early prospective neuroanatomical correlates of toddler irritability and provide preliminary support for the caudate being one important brain region for further investigation regarding the early neural correlates of irritability.

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Understanding irritability through the lens of self-regulatory control processes in children and adolescents: a systematic review

Urben,

Ochoa Williams,

Ben Jemia

et al. 2024

Eur Child Adolesc Psychiatry

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Among youths, pathological irritability is highly prevalent and severely disabling. As a frequent symptom, it often leads to referrals to child and adolescent mental health services. Self-regulatory control (SRC) processes are a set of socio-psycho-physiological processes that allow individuals to adapt to their ever-changing environments. This conceptual framework may enhance the current understanding of the cognitive, emotional, behavioural and social dysregulations underlying irritability. The present systematic review (PROSPERO registration: #CRD42022370390) aims to synthesize existing studies that examine irritability through the lens of SRC processes among youths (< 18 years of age). We conducted a comprehensive literature search among six bibliographic databases: Embase.com, Medline ALL Ovid, APA PsycInfo Ovid, Web of Science Core Collection, the Cochrane Database of Systematic Reviews Wiley and ProQuest Dissertations & Theses A&I. Additional searches were performed using citation tracing strategies. The retrieved reports totalled 2612, of which we included 82 (i.e., articles) from 74 studies. More than 85% of reports were published during the last 6 years, highlighting the topicality of this work. The studies sampled n = 26,764 participants (n = 12,384 girls and n = 12,905 boys, n = 1475 no information) with an average age of 8.08 years (SD = 5.26). The included reports suggest that irritability has an association with lower effortful control, lower cognitive control and delay intolerance. Further, evidence indicates both cross-sectional and longitudinal associations between irritability and a lack of regulation skills for positive and negative emotions, particularly anger. Physiological regulation seems to moderate the association between irritability and psychopathology. Finally, the mutual influence between a child’s irritability and parenting practice has been established in several studies. This review uses the lens of SRC to illustrate the current understanding of irritability in psychopathology, discusses important gaps in the literature, and highlights new avenues for further research.

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Systematic Review and Meta-analysis: Task-based fMRI Studies in Youths With Irritability

Cited by 23 publications

References 81 publications

A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration

A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration

Caudate volume is prospectively associated with irritability in toddlerhood: A preliminary investigation

Understanding irritability through the lens of self-regulatory control processes in children and adolescents: a systematic review

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