Neuroimaging of posttraumatic stress disorder in adults and youth: progress over the last decade on three leading questions of the field.

Almost three decades have passed since the first posttraumatic stress disorder (PTSD) neuroimaging study was published. Since then, the field of clinical neuroscience has made advancements in understanding the neural correlates of PTSD to create more efficacious treatment strategies. While gold-standard psychotherapy options are available, many patients do not respond to them, prematurely drop out, or never initiate treatment. Therefore, elucidating the neurobiological mechanisms that define the disorder can help guide clinician decision-making and develop individualized mechanisms-based treatment options. To this end, this narrative review highlights progress made in the last decade in adult and youth samples on three outstanding questions in PTSD research: (1) Which neural alterations serve as predisposing (pre-exposure) risk factors for PTSD development, and which are acquired (post-exposure) alterations? (2) Which neural alterations can predict treatment outcomes and define clinical improvement? and (3) Can neuroimaging measures be used to define brain-based biotypes of PTSD? While the studies highlighted in this review have made progress in answering the three questions, the field still has much to do before implementing these findings into clinical practice. Overall, to better answer these questions, we suggest that future neuroimaging studies of PTSD should (A) utilize prospective longitudinal designs, collecting brain measures before experiencing trauma and at multiple follow-up time points post-trauma, taking advantage of multi-site collaborations/consortiums; (B) collect two scans to explore changes in brain alterations from pre-to-post treatment and compare changes in neural activation between treatment groups, including longitudinal follow up assessments; and (C) replicate brain-based biotypes of PTSD. By synthesizing recent findings, this narrative review will pave the way for personalized treatment approaches grounded in neurobiological evidence.

Parent Psychopathology and Behavioral Effects on Child Brain-Symptom Networks in the ABCD Study.

OBJECTIVE: Parents play a notable role in the development of child psychopathology. In this study, we investigated the role of parent psychopathology and behaviors on child brain-symptom networks to understand the role of intergenerational transmission of psychopathology. Few studies have documented the interaction of child psychopathology, parent psychopathology, and child neuroimaging. METHOD: We used the baseline cohort of the Adolescent Brain Cognitive Development Study (N = 7,151, female-at-birth = 3,619, aged 9-11 years) to derive brain-symptom networks using sparse canonical correlation analysis with the Child Behavior Checklist and resting-state functional magnetic resonance imaging. We then correlated parent psychopathology symptoms and parental behaviors with child brain-symptom networks. Finally, we used the significant correlations to understand, using the mediation R package, whether parent behaviors mediated the effect of parent psychopathology on child brain connectivity. RESULTS: We observed 3 brain-symptom networks correlated with externalizing (r = 0.19, internalizing (r = 0.17), and neurodevelopmental symptoms (r = 0.18). These corresponded to differences in connectivity between the default mode-default mode, default mode-control, and visual-visual canonical networks. We further detected aspects of parental psychopathology, including personal strength, thought problems, and rule-breaking symptoms to be associated with child brain connectivity. Finally, we found that parental behaviors and symptoms mediate each other's relationship to child brain connectivity. CONCLUSION: The current study suggests that positive parental behaviors can relieve potentially detrimental effects of parental psychopathology, and vice versa, on symptom-correlated child brain connectivity. Altogether, these results provide a framework for future research and potential targets for parents who experience mental health symptoms to help mitigate potential intergenerational transmission of mental illness.

The impact of childhood maltreatment on adaptive emotion regulation strategies.

OBJECTIVE: Childhood maltreatment is a potent known risk factor for psychopathology, accounting for nearly 30% of the risk for mental illness in adulthood. One mechanism by which maltreatment contributes to psychopathology is through impairments in emotion regulation. However, the impact of childhood maltreatment on adaptive regulation strategies remains unclear, particularly across positive and negative emotions. METHODS: Using Mechanical Turk, we recruited a cross-sectional sample of 207 adults (21-69 years) with and without childhood maltreatment exposure to complete an emotion regulation task where they were shown positive and negative emotional pictures and were instructed to reappraise or accept their emotions, alongside a non-instruction comparison condition. Participants rated their emotional intensity following each image, as well as perceived effectiveness of each strategy at the end of each block. We first investigated the impact of image valence and strategy use on the intensity of post-image emotions, followed by interacting both maltreatment exposure and severity with valence and strategy. FINDINGS: Surprisingly, maltreated individuals showed significantly higher emotional intensity compared to non-maltreated individuals, specifically toward positive images (F(2,194.6) = 5.01, p < 0.01). When examining strategy, the use of acceptance to regulate negative emotions was equally effective across all levels of maltreatment severity (F(2,194.6) = 15.93, p < 0.001), while reappraisal was effective only at lower maltreatment levels. CONCLUSION: These findings suggest that experiences of childhood maltreatment exert differential impacts on the ability to regulate positive and negative emotions using key adaptive regulation strategies, which has implications for both psychopathology risk and treatment interventions.

Longitudinal hippocampal circuit change differentiates persistence and remission of pediatric posttraumatic stress disorder.

BACKGROUND: Previous studies have identified functional brain abnormalities in pediatric posttraumatic stress disorder (pPTSD) suggesting altered frontoparietal-subcortical function during emotion processing. However, little is known about how the brain functionally changes over time in recovery versus the persistence of pPTSD. METHODS: This longitudinal study recruited 23 youth with PTSD and 28 typically developing (TD) youth (ages: 8.07-17.99). Within the PTSD group, nine remitted by the 1-year follow-up (Remit) while the remaining 14 persisted (PTSD). At each visit, youth completed an emotional processing task in which they viewed threat and neutral images during functional magnetic resonance imaging (fMRI). Voxelwise activation analyses using linear mixed-effects regression were conducted using a group (TD, Remit, PTSD) by time (baseline, follow-up) by valence (threat, neutral) design. Based on activation findings, a subsequent analysis of hippocampal functional connectivity was performed using a similar model. RESULTS: PTSD youth showed significantly increasing hippocampal activation to threatening images compared to TD youth, while the Remit group showed more similar patterns to TD youth. Subsequent hippocampal functional connectivity analyses reveal the Remit group showed increasing functional connectivity between the hippocampus and visual cortex (V4) while viewing threat stimuli. CONCLUSIONS: These findings represent one of the first preliminary reports of functional brain substrates of persistence and remission in pPTSD. Notably, increased hippocampal activation to threat and decreased connectivity in the hippocampal-V4 network over time may contribute to persistence in pPTSD. These findings suggest potential biomarkers that could be utilized to advance the treatment of pediatric PTSD.