Irritability‐related neural responses to frustrative nonreward in adolescents with trauma histories: A preliminary investigation

Abstract

Irritability, conceptualized as a lowered frustration response threshold to blocked goal attainment (i.e., frustrative nonreward), is a common, detrimental symptom in adolescence. Yet, neural mechanisms of irritability are not well understood. This preliminary study aims to identify irritability‐related neural patterns using a novel frustrative nonreward paradigm. Our study used a diverse sample of N = 31 non‐White adolescent participants (mean age 14.53 years, SD = 1.74; 83.87% Hispanic/Latinx) to improve generalizability. During fMRI acquisition, participants performed a child‐friendly monetary incentive delay task, modified to provide incorrect, negative feedback on performance. Irritability was associated with alterations in amygdala connectivity with basal ganglia, prefrontal, temporal, and parietal regions, and in activation of prefrontal and posterior cortical structures. Across clusters, youths with greater irritability showed activation/connectivity differences between reward blocked versus received conditions in the opposite direction compared to youths with lowered irritability. Alterations in amygdala‐temporoparietal connectivity and lingual gyrus activation demonstrated an altered irritability‐related recovery effect from the previous trial. These findings support the central role of frustrative nonreward as a key irritability pathway. Our work is one of the first to document neural correlates of difficult recovery from frustration characteristic of irritability and provides insight into novel treatment targets for irritability in diverse populations.

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

“…Moreover, youths with clinical diagnoses are likely to receive psychotropic medications, psychotherapy, and/or have environmental risk factors, such as socioeconomic disadvantages and adverse childhood experiences (e.g., 45 ), which have been shown to alter socio-affective brain functions mediating affective symptoms and regulation. 60 However, comprehensive reporting of sample socioeconomic status and race/ethnicity information is rare in the field (i.e., < 30% of the studies reviewed here).…”

“…Importantly, more research is needed to examine the impact of early life adversity and trauma on the etiology and development of childhood irritability, as youths from marginalized and adverse backgrounds represent one of the most vulnerable groups to develop irritability symptoms and deserve timely intervention. 45,61,62 Studies differ in irritability measures. The most commonly used dimensional measures is the ARI, 39 while the most adopted categorical measure is irritability-related modules (i.e., DMDD, ODD, SMD) on the K-SADS.…”

Systematic Review and Meta-Analysis: Task-based fMRI Studies in Youths with Irritability

“…Four studies sampled treatment-seeking and at-risk youths in the local community. 11, 37, 45 Two studies assessed irritability symptoms more broadly in healthy community samples. 20, 26 Three studies constituted part of a large-scale research project (EU-Aggressotype and EU-MATRICS project 38 ; Bipolar offspring study 43 ; IMAGEN 19 ).…”

“…Future studies with large samples that are well-powered to examine irritability by diagnosis are necessary to test this possibility. 10 Moreover, youths with clinical diagnoses are likely to receive psychotropic medications, psychotherapy, and/or have environmental risk factors, such as socioeconomic disadvantages and adverse childhood experiences (e.g., 45 ), which have been shown to alter socio-affective brain functions mediating affective symptoms. 57 These exogenous factors have not been well-characterized and controlled for in the individual studies, further contributing to the lack of convergence.…”

The Future of Psychotherapy for Youth

“…The push for viewing psychopathology dimensionally, rather than categorically, encourages the possibility of viewing chosen dimensions as being transdiagnostic and potentially modifiable across a broad range of clinical disorders (McLaughlin et al, 2021, Hopwood et al, 2020. Moving forward, hopefully dimensions of known processes such as learned helplessness, negative cognitive biases, anhedonia, excessive sadness and irritability, and emotional dysregulation (Chad-Friedman et al, 2021, Brislin et al, 2021, Bufferd et al, 2019, Buffered et al, 2021, Hirsch et al, 2021, Hodgdon et al, 2021, could be the future targets of intervention that lead to deeper insights to why and how internalizing disorders develop, persists, and ultimately remit within a spectrum of dysfunctionality and adaptive functioning for growing adolescents and youth. Recently, there has been a massive push for adopting new approaches to examine psychopathology and to reach new conceptualizations about the nosology, underlying etiology, and subsequent treatments of clinical disorders.…”