Because pediatric anxiety disorders precede the onset of many other problems, successful prediction of response to the first-line treatment, cognitive-behavioral therapy (CBT), could have a major impact. This study evaluates whether structural and resting-state functional magnetic resonance imaging can predict post-CBT anxiety symptoms.

Two datasets were studied: (A) one consisted of n = 54 subjects with an anxiety diagnosis, who received 12 weeks of CBT, and (B) one consisted of n = 15 subjects treated for 8 weeks. Connectome predictive modeling (CPM) was used to predict treatment response, as assessed with the PARS. The main analysis included network edges positively correlated with treatment outcome and age, sex, and baseline anxiety severity as predictors. Results from alternative models and analyses are also presented. Model assessments utilized 1000 bootstraps, resulting in a 95% CI for R2, r, and mean absolute error (MAE).

The main model showed a MAE of approximately 3.5 (95% CI: [3.1–3.8]) points, an R2 of 0.08 [−0.14–0.26], and an r of 0.38 [0.24–0.511]. When testing this model in the left-out sample (B), the results were similar, with an MAE of 3.4 [2.8–4.7], R2−0.65 [−2.29–0.16], and r of 0.4 [0.24–0.54]. The anatomical metrics showed a similar pattern, where models rendered overall low R2.

The analysis showed that models based on earlier promising results failed to predict clinical outcomes. Despite the small sample size, this study does not support the extensive use of CPM to predict outcomes in pediatric anxiety.

Delineation of changes in neural function associated with novel and established treatments for social anxiety disorder (SAD) can advance treatment development. We examined such changes following selective serotonin reuptake inhibitor (SSRI) and attention bias modification (ABM) variant – gaze-contingent music reward therapy (GC-MRT), a first-line and an emerging treatments for SAD.

Eighty-one patients with SAD were allocated to 12-week treatments of either SSRI or GC-MRT, or waitlist (ns = 22, 29, and 30, respectively). Baseline and post-treatment functional magnetic resonance imaging (fMRI) data were collected during a social-threat processing task, in which attention was directed toward and away from threat/neutral faces.

Patients who received GC-MRT or SSRI showed greater clinical improvement relative to patients in waitlist. Compared to waitlist patients, treated patients showed greater activation increase in the right inferior frontal gyrus and anterior cingulate cortex when instructed to attend toward social threats and away from neutral stimuli. An additional anterior cingulate cortex cluster differentiated between the two active groups. Activation in this region increased in ABM and decreased in SSRI. In the ABM group, symptom change was positively correlated with neural activation change in the dorsolateral prefrontal cortex.

Brain function measures show both shared and treatment-specific changes following ABM and SSRI treatments for SAD, highlighting the multiple pathways through which the two treatments might work. Treatment-specific neural responses suggest that patients with SAD who do not fully benefit from SSRI or ABM may potentially benefit from the alternative treatment, or from a combination of the two.

ClinicalTrials.gov, Identifier: NCT03346239. https://clinicaltrials.gov/ct2/show/NCT03346239

In a recent eye-tracking study we found a differential dwell time pattern for negatively-valenced and neutral faces among patients with posttraumatic stress disorder (PTSD), trauma-exposed healthy control (TEHCs), and healthy control (HC) participants. Here, we explored whether these group differences relate to resting-state functional connectivity (rsFC) patterns of brain areas previously linked to both attention processes and PTSD. These encompass the amygdala, dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), and nucleus accumbens (NAcc).

Ten minutes magnetic resonance imaging rsFC scans were recorded in 17 PTSD patients, 21 TEHCs, and 16 HCs. Participants then completed a free-viewing eye-tracking task assessing attention allocation outside the scanner. Dwell time on negatively-valenced stimuli (DT%) were assessed relative to functional connectivity in the aforementioned seed regions of interest (amygdala, dACC, dlPFC, vlPFC, and NAcc) to whole-brain voxel-wise rsFC.

As previously reported, group differences occurred in attention allocation to negative-valence stimuli, with longer dwell time on negatively valence stimuli in the PTSD and TEHC groups than the HC group. Higher DT% correlated with weaker NAcc-orbitofrontal cortex (OFC) connectivity in patients with PTSD. Conversely, a positive association emerged in the HC group between DT% and NAcc-OFC connectivity.

While exploratory in nature, present findings may suggest that reward-related brain areas are involved in disengaging attention from negative-valenced stimuli, and possibly in regulating ensuing negative emotions.

Many individuals with posttraumatic stress disorder (PTSD) have limited access to first-line treatments, warranting the development of remotely-delivered treatments. Attention bias modification (ABM), targeting perturbed threat-related attentional patterns, shows promise when delivered in-person. However, previous studies found ABM to be ineffective when delivered remotely. Randomized clinical trials usually applied two variations of ABM: ABM away from threat or attention control training (ACT) balancing attention between threat-related and neutral stimuli. We tested remotely-delivered ACT/ABM with tighter supervision and video-based interactions that resemble in-clinic protocols. We expected to replicate the results of in-clinic trials, in which ACT outperformed ABM for PTSD.

In this double-blinded, parallel-group randomized controlled trial, 60 patients diagnosed with PTSD were randomized (ABM n = 30; ACT n = 30). Patients performed eight bi-weekly remotely-delivered supervised ABM/ACT sessions. Symptoms were assessed pre- and post-treatment with Clinician-Administered PTSD Scale 5 (CAPS-5) severity score and PTSD diagnosis as the primary outcomes. Current depressive episode, current anxiety-related comorbidity, and time elapsed since the trauma were examined as potential moderators of treatment outcome.

Significant decrease in CAPS-5 severity scores and PTSD diagnosis was observed following both ACT and ABM with no between-group difference. Patients without depression or whose trauma occurred more recently had greater symptom reduction in the ACT than the ABM group.

Contrary to our expectation, symptoms decreased similarly following ACT and ABM. Moderator analyses suggest advantage for ACT in non-depressed patients and patients whose trauma occurred more recently. Further refinements in remotely-delivered ABM/ACT may be needed.

Eye-tracking-based attentional research implicates sustained attention to threat in posttraumatic stress disorder (PTSD). However, most of this research employed small stimuli set-sizes, small samples that did not include both trauma-exposed healthy participants and non-trauma-exposed participants, and generally failed to report the reliability of used tasks and attention indices. Here, using an established eye-tracking paradigm, we explore attention processes to different negatively-valenced cues in PTSD while addressing these limitations.

PTSD patients (n = 37), trauma-exposed healthy controls (TEHC; n = 34), and healthy controls (HC; n = 30) freely viewed three blocks of 30 different matrices of faces, each presented for 6 s. Each block consisted of matrices depicting eight negatively-valenced faces (anger, fear, or sadness) and eight neutral faces. Gaze patterns on negative and neural areas of interest were compared. Internal consistency and test-retest reliability were evaluated for the entire sample and within groups.

The two trauma-exposed groups dwelled longer on negatively-valenced faces over neutral faces, while HC participants showed the opposite pattern. This attentional bias was more prominent in the PTSD than the TEHC group. Similar results emerged for first-fixation dwell time, but with no differences between the two trauma-exposed groups. No group differences emerged for first-fixation latency or location. Internal consistency and 1-week test-retest reliability were adequate, across and within groups.

Sustained attention on negatively-valenced stimuli emerges as a potential target for therapeutic intervention in PTSD designed to divert attention away from negatively-valenced stimuli and toward neutral ones.

Previous randomized controlled trials (RCTs) suggest that attention control therapy (ACT), targeting aberrant fluctuations of attention toward and away from threats in patients with PTSD, may be effective in reducing symptoms. The current RCT examined whether the use of personalized-trauma stimuli enhances ACT efficacy in patients with PTSD. Additional moderators of treatment outcome were tested on an exploratory basis.

Sixty patients with PTSD were randomly assigned to either personalized ACT, non-personalized ACT, or a control condition. Changes in symptoms were examined across pre-treatment, post-treatment, and a 3-month follow-up. Attentional interference was examined pre- and post-treatment. Baseline clinical and cognitive indices as well as the time elapsed since the trauma were tested as potential moderators of treatment outcome.

A significant reduction in clinical symptoms was noted for all three conditions with no between-group differences. Attention bias variability decreased following ACT treatment. Personalized ACT was more effective relative to the control condition when less time had elapsed since the trauma. Baseline clinical and cognitive indices did not moderate treatment outcome.

In this RCT of patients with PTSD, ACT was no more effective in reducing PTSD symptoms than a control condition. The data also suggest a potential benefit of personalized ACT for patients who experienced their trauma more recently.

While taxonomy segregates anxiety symptoms into diagnoses, patients typically present with multiple diagnoses; this poses major challenges, particularly for youth, where mixed presentation is particularly common. Anxiety comorbidity could reflect multivariate, cross-domain interactions insufficiently emphasized in current taxonomy. We utilize network analytic approaches that model these interactions by characterizing pediatric anxiety as involving distinct, inter-connected, symptom domains. Quantifying this network structure could inform views of pediatric anxiety that shape clinical practice and research.

Participants were 4964 youths (ages 5–17 years) from seven international sites. Participants completed standard symptom inventory assessing severity along distinct domains that follow pediatric anxiety diagnostic categories. We first applied network analytic tools to quantify the anxiety domain network structure. We then examined whether variation in the network structure related to age (3-year longitudinal assessments) and sex, key moderators of pediatric anxiety expression.

The anxiety network featured a highly inter-connected structure; all domains correlated positively but to varying degrees. Anxiety patients and healthy youth differed in severity but demonstrated a comparable network structure. We noted specific sex differences in the network structure; longitudinal data indicated additional structural changes during childhood. Generalized-anxiety and panic symptoms consistently emerged as central domains.

Pediatric anxiety manifests along multiple, inter-connected symptom domains. By quantifying cross-domain associations and related moderation effects, the current study might shape views on the diagnosis, treatment, and study of pediatric anxiety.

Despite extensive research, symptom structure of posttraumatic stress disorder (PTSD) is highly debated. The network approach to psychopathology offers a novel method for understanding and conceptualizing PTSD. However, extant studies have mainly used small samples and self-report measures among sub-clinical populations, while also overlooking co-morbid depressive symptoms.

PTSD symptom network topology was estimated in a sample of 1489 treatment-seeking veteran patients based on a clinician-rated PTSD measure. Next, clinician-rated depressive symptoms were incorporated into the network to assess their influence on PTSD network structure. The PTSD-symptom network was then contrasted with the network of 306 trauma-exposed (TE) treatment-seeking patients not meeting full criteria for PTSD to assess corresponding network differences. Finally, a directed acyclic graph (DAG) was computed to estimate potential directionality among symptoms, including depressive symptoms and daily functioning.

The PTSD symptom network evidenced robust reliability. Flashbacks and getting emotionally upset by trauma reminders emerged as the most central nodes in the PTSD network, regardless of the inclusion of depressive symptoms. Distinct clustering emerged for PTSD and depressive symptoms within the comorbidity network. DAG analysis suggested a key triggering role for re-experiencing symptoms. Network topology in the PTSD sample was significantly distinct from that of the TE sample.

Flashbacks and psychological reactions to trauma reminders, along with their strong connections to other re-experiencing symptoms, have a pivotal role in the clinical presentation of combat-related PTSD among veterans. Depressive and posttraumatic symptoms constitute two separate diagnostic entities, but with meaningful between-disorder connections, suggesting two mutually-influential systems.

Combat exposure is associated with elevated risk for post-traumatic stress disorder (PTSD). Despite considerable research on PTSD symptom clustering, it remains unknown how symptoms of PTSD re-organize following combat. Network analysis provides a powerful tool to examine such changes.

A network analysis approach was taken to examine how symptom networks change from pre- to post-combat using longitudinal prospective data from a cohort of infantry male soldiers (Mage = 18.8 years). PTSD symptoms measured using the PTSD Checklist (PCL) were assessed after 6 months of combat training but before deployment and again after 6 months of combat (Ns = 910 and 725 at pre-deployment and post-combat, respectively)

Stronger connectivity between PTSD symptoms was observed post-combat relative to pre-deployment (global strength values of the networks were 7.54 pre v. 7.92 post; S = .38, p < 0.05). Both the re-experiencing symptoms cluster (1.92 v. 2.12; S = .20, p < 0.03) and the avoidance symptoms cluster (2.61 v. 2.96; S = .35, p < 0.005) became more strongly inter-correlated post-combat. Centrality estimation analyses revealed that psychological reaction to triggers was central and linked the intrusion and avoidance sub-clusters at post-combat. The strength of associations between the arousal and reactivity symptoms cluster remained stable over time (1.85 v. 1.83; S = .02, p = .92).

Following combat, PTSD symptoms and particularly the re-experiencing and avoidance clusters become more strongly inter-correlated, indicating high centrality of trigger-reactivity symptoms.

Anxiety symptoms gradually emerge during childhood and adolescence. Individual differences in behavioral inhibition (BI), an early-childhood temperament, may shape developmental paths through which these symptoms arise. Cross-sectional research suggests that level of early-childhood BI moderates associations between later anxiety symptoms and threat-related amygdala–prefrontal cortex (PFC) circuitry function. However, no study has characterized these associations longitudinally. Here, we tested whether level of early-childhood BI predicts distinct evolving associations between amygdala–PFC function and anxiety symptoms across development.

Eighty-seven children previously assessed for BI level in early childhood provided data at ages 10 and/or 13 years, consisting of assessments of anxiety and an fMRI-based dot-probe task (including threat, happy, and neutral stimuli). Using linear-mixed-effects models, we investigated longitudinal changes in associations between anxiety symptoms and threat-related amygdala–PFC connectivity, as a function of early-childhood BI.

In children with a history of high early-childhood BI, anxiety symptoms became, with age, more negatively associated with right amygdala–left dorsolateral-PFC connectivity when attention was to be maintained on threat. In contrast, with age, low-BI children showed an increasingly positive anxiety–connectivity association during the same task condition. Behaviorally, at age 10, anxiety symptoms did not relate to fluctuations in attention bias (attention bias variability, ABV) in either group; by age 13, low-BI children showed a negative anxiety–ABV association, whereas high-BI children showed a positive anxiety–ABV association.

Early-childhood BI levels predict distinct neurodevelopmental pathways to pediatric anxiety symptoms. These pathways involve distinct relations among brain function, behavior, and anxiety symptoms, which may inform diagnosis and treatment.

Aberrations in reward and penalty processing are implicated in depression and putatively reflect altered dopamine signalling. This study exploits the advantages of a placebo-controlled design to examine how a novel D2 antagonist with adjunctive antidepressant properties modifies activity in the brain's reward network in depression.

We recruited 43 medication-naïve subjects across the range of depression severity (Beck's Depression Inventory-II score range: 0–43), including healthy volunteers, as well as people meeting full-criteria for major depressive disorder. In a double-blind placebo-controlled cross-over design, all subjects received either placebo or lurasidone (20 mg) across two visits separated by 1 week. Functional magnetic resonance imaging with the Monetary Incentive Delay (MID) task assessed reward functions via neural responses during anticipation and receipt of gains and losses. Arterial spin labelling measured cerebral blood flow (CBF) at rest.

Lurasidone altered fronto-striatal activity during anticipation and outcome phases of the MID task. A significant three-way Medication-by-Depression severity-by-Outcome interaction emerged in the anterior cingulate cortex (ACC) after correction for multiple comparisons. Follow-up analyses revealed significantly higher ACC activation to losses in high- v. low depression participants in the placebo condition, with a normalisation by lurasidone. This effect could not be accounted for by shifts in resting CBF.

Lurasidone acutely normalises reward processing signals in individuals with depressive symptoms. Lurasidone's antidepressant effects may arise from reducing responses to penalty outcomes in individuals with depressive symptoms.