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IMPORTANCE: More than 10% of children experience sexual, physical, or emotional abuse, and abuse experienced during sensitive neurodevelopmental periods is associated with a greater risk of psychiatric disorders. OBJECTIVE: To investigate the extent to which a history of abuse is associated with alterations in the intrinsic functional connectome of the adult brain independent from the restriction of associated psychiatric conditions. DESIGN, SETTING, AND PARTICIPANTS: This cohort study assessed data from 768 adult participants from the greater Sydney, Australia, area who were included in the study without diagnostic restrictions and categorized based on a history of childhood sexual, physical, and/or emotional abuse. Data were collected from January 1, 2009, to December 31, 2015; data analysis was performed from October 1, 2020, to March 31, 2022. MAIN OUTCOMES AND MEASURES: Outcomes were structured psychiatric interview responses, self-report of the frequency and extent of various types of negative experiences in childhood and adolescence, and intrinsic functional connectivity derived from 5 functional magnetic resonance imaging tasks and estimated among 436 brain regions, comprising intranetwork and internetwork connectivity of 8 large-scale brain networks. RESULTS: Among the 647 individuals with usable data (330 female [51.0%]; mean [SD] age, 33.3 [12.0] years; age range, 18.2-69.2 years), history of abuse was associated with greater likelihood of a current psychiatric illness (odds ratio, 4.55; 95% CI, 3.07-6.72; P < .001) and with greater depressive, anxiety, and stress symptoms (mean difference, 20.4; 95% CI, 16.1-24.7; P < .001). An altered connectome signature of higher connectivity within somatomotor, dorsal, and ventral attention networks and between these networks and executive control and default mode networks was observed in individuals with a history of abuse experienced during childhood (n = 127) vs those without a history of abuse (n = 442; mean diff

Military personnel experience high trauma load that can change brain circuitry leading to impaired inhibitory control and posttraumatic stress disorder (PTSD). Inhibitory control processing may be particularly vulnerable to developmental and interpersonal trauma. This study examines the differential role of cumulative pre-deployment trauma and timing of trauma on inhibitory control using the Go/NoGo paradigm in a military population. The Go/NoGo paradigm was administered to 166 predominately male army combat personnel at pre- and post-deployment. Linear mixed models analyze cumulative trauma, trauma onset, and post-deployment PTSD symptoms on NoGo-N2 and NoGo-P3 amplitude and latency across deployment. Here we report, NoGo-N2 amplitude increases and NoGo-P3 amplitude and latency decreases in those with high prior interpersonal trauma across deployment. Increases in NoGo-P3 amplitude following adolescent-onset trauma and NoGo-P3 latency following childhood-onset and adolescent-onset trauma are seen across deployment. Arousal symptoms positively correlated with conflict monitoring. Our findings support the cumulative trauma load and sensitive period of trauma exposure models for inhibitory control processing in a military population. High cumulative interpersonal trauma impacts conflict monitoring and response suppression and increases PTSD symptoms whereas developmental trauma differentially impacts response suppression. This research highlights the need for tailored strategies for strengthening inhibitory control, and that consider timing and type of trauma in military personnel.

BACKGROUND: Posttraumatic Stress Disorder is associated with emotion regulation difficulties. However, our understanding of these difficulties has been limited by the reliance of previous work on retrospective trait self-reports, which are unable to capture dynamic, ecologically-valid use of emotion regulation strategies. METHODS: To address this issue, this study used an ecological momentary assessment (EMA) design to understand the impact of PTSD on emotion regulation in daily life. We conducted an EMA study in a trauma exposed sample with varying levels of PTSD severity (N = 70; 7 days; 423 observations). RESULTS: We found that PTSD severity was linked to greater use of disengagement and perseverative-based strategies to manage negative emotions, regardless of emotional intensity. LIMITATIONS: Study design did not allow investigation into the temporal use of emotion regulation strategies and small sample size. CONCLUSIONS: This pattern of responding to emotions may interfere with engaging with the fear structure and thus impair emotion processing in current frontline treatments; clinical implications are discussed.

OBJECTIVE: Cognitive impairment is consistently reported in bipolar disorder (BD), but few studies have characterised which memory component processes are affected. Further, it is unknown whether the component processes underlying memory impairment are moderated by sex. The present study examined diagnosis and sex differences in both verbal and visual memory/learning domains in patients with BD and psychiatrically healthy controls. METHOD: Verbal and visual memory/learning were measured using the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R). 114 patients with BD (n = 50 males, n = 64 females), were compared to 105 psychiatrically healthy controls (n = 42 males, n = 63 females). RESULTS: Patients with BD had worse performance in verbal and visual immediate and total recall, verbal and visual delayed free recall, and verbal recognition discrimination scores, but there were no group differences in learning slopes and cumulative learning index scores. There were trends for BD females to outperform BD males in visual memory/learning free recall and cumulative learning, but these results did not survive multiple testing correction. These findings did not change in a secondary sensitivity analysis comparing only strictly euthymic BD patients to controls (n = 64). CONCLUSION: The present study found trait-like verbal and visual memory/learning impairment in BD that was attributable to deficient encoding and/or consolidation processes rather than deficits in learning. We did not find marked sex differences in either visual or verbal memory/learning measures, although some trend level effects were apparent and deserve exploration in future studies.

BACKGROUND: Prolonged Exposure (PE), a trauma-focused therapy, is one of the most efficacious treatments available for PTSD. However, many people with PTSD do not lose their diagnosis following delivery of PE. The Unified Protocol (UP) for Transdiagnostic Treatment of Emotional Disorders is a non-trauma focused treatment that may offer an alternative treatment for PTSD. METHODS: This paper describes the study protocol for IMPACT, an assessor-blinded randomized controlled trial that examines the non-inferiority of UP relative to PE for participants who meet DSM-5 criteria for current PTSD. One hundred and twenty adult participants with PTSD will be randomized to receive either 10 × 90-min sessions of UP or PE with a trained provider. The primary outcome is severity of PTSD symptoms assessed by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at post-treatment. DISCUSSION: While evidence-based treatments are available for PTSD, high levels of treatment dropout and non-response require new approaches to be tested. The UP is based on emotion regulation theory and is effective in treating anxiety and depressive disorders, however, there has been limited application to PTSD. This is the first rigorous study comparing UP to PE in a non-inferiority randomized controlled trial and may help improve clinical outcomes for those with PTSD. TRIAL REGISTRATION: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry, Trial ID (ACTRN12619000543189).

Aims Refugees typically spend years in a state of protracted displacement prior to permanent resettlement. Little is known about how various prior displacement contexts influence long-term mental health in resettled refugees. In this study, we aimed to determine whether having lived in refugee camps v. community settings prior to resettlement impacted the course of refugees' psychological distress over the 4 years following arrival in Australia. Methods Participants were 1887 refugees who had taken part in the Building a New Life in Australia study, which comprised of five annual face-to-face or telephone surveys from the year of first arrival in Australia. Results Latent growth curve modelling revealed that refugees who had lived in camps showed greater initial psychological distress (as indexed by the K6) and faster decreases in psychological distress in the 4 years after resettling in Australia, compared to those who had lived in community settings. Investigation of refugee camp characteristics revealed that poorer access to services in camps was associated with greater initial distress after resettlement, and greater ability to meet one's basic needs in camps was associated with faster decreases in psychological distress over time. Conclusions These findings highlight the importance of the displacement context in influencing the course of post-resettlement mental health. Increasing available services and meeting basic needs in the displacement environment may promote better mental health outcomes in resettled refugees.

Background Trauma- and stress-related disorders, such as post-traumatic stress disorder (PTSD), are more common in females than in males. Sex hormones affect learning and emotional memory formation and may be associated with the development of PTSD. Most previous studies have indexed these hormones in isolation. Objectives: To investigate associations of sex hormones and cortisol during memory consolidation on the development of intrusive memories. Methods: We employed an experimental trauma film paradigm in 61 healthy women and indexed salivary testosterone, progesterone, estradiol, and cortisol on day one and day two post experimental trauma exposure and their effects on intrusion frequency, distress, and vividness. Intrusive trauma memories were indexed by means of a diary in which participants documented intrusion frequency, distress, and vividness. Results and conclusion: Participants reported an average of 5.3 intrusions over the course of seven days (SD = 4.6, range 0-26). Progesterone, and estradiol indexed on day one predicted intrusion frequency, with higher progesterone and lower estradiol predicting more intrusive memories (p-values AUC progesterone 0.01 and estradiol 0.02). There was no evidence for associations between hormone concentration indices on day two and intrusion outcomes. Further research on the roles of gonadal and adrenal hormones in trauma memory formation is needed to advance our efforts to understand their influence on PTSD development.

Negative self-beliefs are a core feature of psychopathology. Despite this, we have a limited understanding of the brain mechanisms by which negative self-beliefs are cognitively restructured. Using a novel paradigm, we had participants use Socratic questioning techniques to restructure negative beliefs during ultra-high resolution 7-Tesla functional magnetic resonance imaging (UHF 7 T fMRI) scanning. Cognitive restructuring elicited prominent activation in a fronto-striato-thalamic circuit, including the mediodorsal thalamus (MD), a group of deep subcortical nuclei believed to synchronize and integrate prefrontal cortex activity, but which has seldom been directly examined with fMRI due to its small size. Increased activity was also identified in the medial prefrontal cortex (MPFC), a region consistently activated by internally focused mental processing, as well as in lateral prefrontal regions associated with regulating emotional reactivity. Using Dynamic Causal Modelling (DCM), evidence was found to support the MD as having a strong excitatory effect on the activity of regions within the broader network mediating cognitive restructuring. Moreover, the degree to which participants modulated MPFC-to-MD effective connectivity during cognitive restructuring predicted their individual tendency to engage in repetitive negative thinking. Our findings represent a major shift from a cortico-centric framework of cognition and provide important mechanistic insights into how the MD facilitates key processes in cognitive interventions for common psychiatric disorders. In addition to relaying integrative information across basal ganglia and the cortex, we propose a multifaceted role for the MD whose broad excitatory pathways act to increase synchrony between cortical regions to sustain complex mental representations, including the self.

It has recently been suggested that a deficit in time processing may be considered a cognitive marker of Post-Traumatic Stress Disorder (PTSD). However, the neural correlates of this cognitive deficit in PTSD remain unknown. Voxel-based morphometry and supra-second perceptual time processing data from 8 participants with PTSD and 19 healthy controls have been examined. In line with previous investigations, PTSD patients overestimated the duration of the displayed stimuli. Moreover, their time estimation was more variable than that of controls. Critically, compared to controls, a higher grey matter volume was reported in most of neural regions of PTSD canonically associated with supra-second perceptual timing. These data provide preliminary evidence that the abnormal neuroplasticity of this neural network may be responsible for the altered experience of time in PTSD.

AIMS: Refugees typically spend years in a state of protracted displacement prior to permanent resettlement. Little is known about how various prior displacement contexts influence long-term mental health in resettled refugees. In this study, we aimed to determine whether having lived in refugee camps v. community settings prior to resettlement impacted the course of refugees' psychological distress over the 4 years following arrival in Australia. METHODS: Participants were 1887 refugees who had taken part in the Building a New Life in Australia study, which comprised of five annual face-to-face or telephone surveys from the year of first arrival in Australia. RESULTS: Latent growth curve modelling revealed that refugees who had lived in camps showed greater initial psychological distress (as indexed by the K6) and faster decreases in psychological distress in the 4 years after resettling in Australia, compared to those who had lived in community settings. Investigation of refugee camp characteristics revealed that poorer access to services in camps was associated with greater initial distress after resettlement, and greater ability to meet one's basic needs in camps was associated with faster decreases in psychological distress over time. CONCLUSIONS: These findings highlight the importance of the displacement context in influencing the course of post-resettlement mental health. Increasing available services and meeting basic needs in the displacement environment may promote better mental health outcomes in resettled refugees.

Sleep may contribute to the long-lasting consolidation and processing of emotional memories. Experimental fear conditioning and extinction paradigms model the development, maintenance, and treatment of anxiety disorders. The literature provides compelling evidence for the involvement of rapid eye movement (REM) sleep in the consolidation of such memories. This meta-analysis correlated polysomnographic sleep findings with psychophysiological reactivity to the danger (CS+) and safety stimuli (CS-), to clarify the specific role of sleep stages before and after fear conditioning, extinction learning and extinction recall. Overall, there was evidence that more pre-learning sleep stage two and less slow wave sleep was associated with higher psychophysiological reactivity to the safety stimulus during extinction learning. Preliminary evidence found here support the role of REM sleep during the post-extinction consolidation sleep phase in clinical populations with disrupted sleep, but not in healthy controls. Furthermore, the meta-regressions found that sex moderated the associations between sleep and psychophysiological reactivity throughout the paradigm providing evidence for diverging correlations in male and females. Specifically, increased post-extinction REM was associated with poorer extinction and safety recall in females while the opposite was found in males. These results have implications for future research in the role of sleep in emotional memory processing.

• PTSD with alexithymia and PTSD-related emotion numbing show unique neural profiles. • Alexithymia is linked to alterations in the default mode network. • Alexithymia is associated with emotional meta-cognition and attentional control. • PTSD-related emotion numbing is linked to alterations in the salience network. • Emotion numbing is linked to disorder-level negative affect. Alexithymia is very common among those with Post-traumatic stress disorder with estimates suggesting that as many as 42% of individuals with PTSD exhibit clinically-relevant alexithymia. One proposed explanation for this comorbidity is that alexithymia symptoms exhibit structural overlap with PTSD-related emotion numbing. Given the need to identify via objective measurement whether alexithymia and emotional numbing are overlapping or different experiences, a review of neural circuitry involved in these conditions is warranted. In this paper, we briefly discuss emotion processing in Alexithymia and PTSD, presenting a PRISMA systematic review of the relevant functional neuroimaging studies. Our results suggest that alexithymia is linked to alterations in the Default Mode Network (DMN) while PTSD-related emotion numbing appears to be primarily linked to alterations in the salience network. Our results suggest that emotion numbing may be linked to neural networks associated with disorder-level negative affect while alexithymia is linked to alterations in neural networks associated with emotional meta-cognition and attentional control, providing evidence that these constructs are at least partially distinct in the brain. This has important clinical implications and may inform the selection of appropriate treatments. The impact of the review may be limited due to cross-study variations in control groups, different trauma histories, individual differences and emotion processing paradigms utilised.

BACKGROUND: The endocannabinoid system is gaining increasing attention as a favorable target for improving posttraumatic stress disorder (PTSD) treatments. Exposure therapy is the gold-standard treatment for PTSD, and fear extinction learning is a key concept underlying successful exposure. METHODS: This study examined the role of genetic endocannabinoid polymorphisms in a fear extinction paradigm with PTSD compared to healthy participants (N = 220). Participants provided saliva for genotyping, completed a fear conditioning and extinction task, with blood samples taken before and after the task (n = 57). Skin conductance was the outcome and was analyzed using mixed models. RESULTS: Results for cannabinoid receptor type 1 polymorphisms suggested that minor alleles of rs2180619 and rs1049353 were associated with poorer extinction learning in PTSD participants. The minor allele of the fatty acid amide hydrolase (FAAH) polymorphism rs324420 was associated with worse extinction in PTSD participants. Subanalysis of healthy participants (n = 57) showed the FAAH rs324420 genotype effect was dependent on plasma arachidonoyl ethanolamide (AEA) level, but not oleoylethanolamide or 2-arachidonoyl glycerol. Specifically, higher but not lower AEA levels in conjunction with the minor allele of FAAH rs324420 were associated with better extinction learning. CONCLUSIONS: These findings provide translational evidence that cannabinoid receptor 1 and AEA are involved in extinction learning in humans. FAAH rs324420's effect on fear extinction is moderated by AEA plasma level in healthy controls. These findings imply that FAAH inhibitors may be effective for targeting anxiety in PTSD, but this effect needs to be explored further in clinical populations.

BACKGROUND: Although trauma-focused cognitive behavioral therapy (TF-CBT) is the frontline treatment for posttraumatic stress disorder (PTSD), at least one-third of patients are treatment nonresponders. This study aimed to identify neural markers of treatment response, specifically the prediction of remission of specific PTSD symptoms. METHODS: This study assessed PTSD treatment-seeking patients (n = 40) before TF-CBT during functional magnetic brain resonance imaging (fMRI) when they processed fearful, sad, happy, and neutral faces. Patients underwent nine sessions of TF-CBT and were independently assessed on the Clinician-Administered PTSD Scale (CAPS) following treatment. Treatment responders and nonresponders were compared with healthy controls (n = 40). The severity of PTSD was assessed with the CAPS. fMRI responses were calculated for each emotion face compared to neutral contrast, which were correlated with reduction in PTSD severity from pretreatment to posttreatment. Treatment response was categorized by at least 50% reduction in the severity of PTSD. RESULTS: The activation of left insula during the processing of both sad and fearful faces was associated with a greater reduction of fear but not with dysphoric symptoms after treatment. Connectivity of the left insula to the pregenual anterior cingulate cortex was associated with poorer response to treatment. Responders and controllers had similar levels of activation and connectivity and were different from nonresponders. CONCLUSIONS: Positive response to TF-CBT is predicted during emotion processing by normal levels of recruitment of neural networks implicated in emotional information. These findings suggest that distinct neural networks are predictive of PTSD fear and dysphoric symptom reduction following TF-CBT.

Background: High-income countries like Australia play a vital role in resettling refugees from around the world, half of whom are children and adolescents. Informed by an ecological framework, this study examined the post-migration adjustment of refugee children and adolescents 2-3 years after arrival to Australia. We aimed to estimate the overall rate of adjustment among young refugees and explore associations with adjustment and factors across individual, family, school, and community domains, using a large and broadly representative sample. Method(s): Data were drawn from Wave 3 of the Building a New Life in Australia (BNLA) study, a nationally representative, longitudinal study of settlement among humanitarian migrants in Australia. Caregivers of refugee children aged 5-17 (N = 694 children and adolescents) were interviewed about their children's physical health and activity, school absenteeism and achievement, family structure and parenting style, and community and neighbourhood environment. Parent and child forms of the Strengths and Difficulties Questionnaire (SDQ) were completed by caregivers and older children to assess social and emotional adjustment. Result(s): Sound adjustment according to the SDQ was observed regularly among young refugees, with 76-94% (across gender and age) falling within normative ranges. Comparison with community data for young people showed that young refugees had comparable or higher adjustment levels than generally seen in the community. However, young refugees as a group did report greater peer difficulties. Bivariate and multivariate linear regression analyses showed that better reported physical health and school achievement were associated with higher adjustment. Furthermore, higher school absenteeism and endorsement of a hostile parenting style were associated with lower adjustment. Conclusion(s): This is the first study to report on child psychosocial outcomes from the large, representative longitudinal BNLA study. Our find

Research has revealed reduced temporal discounting (i.e., increased capacity to delay reward) and altered interoceptive awareness in anorexia nervosa (AN). In line with the research linking temporal underestimation with a reduced tendency to devalue a reward and reduced interoceptive awareness, we tested the hypothesis that time duration might be underestimated in AN. Our findings revealed that patients with AN displayed lower timing accuracy in the form of timing underestimation compared with controls. These results were not predicted by clinical, demographic factors, attention, and working memory performance of the participants. The evidence of a temporal underestimation bias in AN might be clinically relevant to explain their abnormal motivation in pursuing a long-term restrictive diet, in line with the evidence that increasing the subjective temporal proximity of remote future goals can boost motivation and the actual behavior to reach them.

BACKGROUND: High-income countries like Australia play a vital role in resettling refugees from around the world, half of whom are children and adolescents. Informed by an ecological framework, this study examined the post-migration adjustment of refugee children and adolescents 2-3 years after arrival to Australia. We aimed to estimate the overall rate of adjustment among young refugees and explore associations with adjustment and factors across individual, family, school, and community domains, using a large and broadly representative sample. METHODS: Data were drawn from Wave 3 of the Building a New Life in Australia (BNLA) study, a nationally representative, longitudinal study of settlement among humanitarian migrants in Australia. Caregivers of refugee children aged 5-17 (N = 694 children and adolescents) were interviewed about their children's physical health and activity, school absenteeism and achievement, family structure and parenting style, and community and neighbourhood environment. Parent and child forms of the Strengths and Difficulties Questionnaire (SDQ) were completed by caregivers and older children to assess social and emotional adjustment. RESULTS: Sound adjustment according to the SDQ was observed regularly among young refugees, with 76-94% (across gender and age) falling within normative ranges. Comparison with community data for young people showed that young refugees had comparable or higher adjustment levels than generally seen in the community. However, young refugees as a group did report greater peer difficulties. Bivariate and multivariate linear regression analyses showed that better reported physical health and school achievement were associated with higher adjustment. Furthermore, higher school absenteeism and endorsement of a hostile parenting style were associated with lower adjustment. CONCLUSIONS: This is the first study to report on child psychosocial outcomes from the large, representative longitudinal BNLA study. Our findings i

BACKGROUND: Posttraumatic stress disorder (PTSD) occurs twice as commonly amongst women as men. Two common domains of trauma, network trauma and gender based violence (GBV), may contribute to this gender difference in PTSD rates. We examined data from a nationally representative sample of the Australian population to clarify the characteristics of these two trauma domains in their contributions to PTSD rates in men and women. METHODS: We drew on data from the 2007 Australian National Survey of Mental Health and Well-being to assess gender differences across a comprehensive range of trauma domains, including (1) prevalence of lifetime exposure; (2) identification of an index trauma or DSM-IV Criterion A event; and (3) the likelihood of developing full DSM-IV PTSD symptoms once an index trauma was identified. RESULTS: Men reported more traumatic events (TEs) overall but women reported twice the prevalence of lifetime PTSD (women, 13.4%; men, 6.3%). Women reported a threefold higher level of exposure to GBV and were seven times more likely to nominate GBV as the index trauma as compared to men. Women were twice more likely than men to identify a network trauma as the index trauma and more likely to meet full PTSD symptoms in relation to that event (women, 20.6%; men, 14.6%). CONCLUSION: Women are more likely to identify GBV and network trauma as an index trauma. Women's far greater exposure to GBV contributes to their higher prevalence of PTSD. Women are markedly more likely to develop PTSD when network trauma is identified as the index trauma. Preventing exposure to GBV and providing timely interventions for acute psychological reactions following network trauma may assist in reducing PTSD rates amongst women.

Although intrusive memories are characteristic of many psychological disorders, the neurobiological underpinning of these involuntary recollections are largely unknown. In this study we used functional magentic resonance imaging (fMRI) to identify the neural networks associated with encoding of negative stimuli that are subsequently experienced as intrusive memories. Healthy partipants (N = 42) viewed negative and neutral images during a visual/verbal processing task in an fMRI context. Two days later they were assessed on the Impact of Event Scale for occurrence of intrusive memories of the encoded images. A sub-group of participants who reported significant intrusions (n = 13) demonstrated stronger activation in the amygdala, bilateral ACC and parahippocampal gyrus during verbal encoding relative to a group who reported no intrusions (n = 13). Within-group analyses also revealed that the high intrusion group showed greater activity in the dorsomedial (dmPFC) and dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus and occipital regions during negative verbal processing compared to neutral verbal processing. These results do not accord with models of intrusions that emphasise visual processing of information at encoding but are consistent with models that highlight the role of inhibitory and suppression processes in the formation of subsequent intrusive memories.

Our study explores inhibitory control across a range of widely recognised memory and behavioural tasks. Eighty-seven never-depressed participants completed a series of tasks designed to measure inhibitory control in memory and behaviour. Specifically, a variant of the selective retrieval-practice and the Think/No-Think tasks were employed as measures of memory inhibition. The Stroop-Colour Naming and the Go/No-Go tasks were used as measures of behavioural inhibition. Participants completed all 4 tasks. Task presentation order was counterbalanced across 3 separate testing sessions for each participant. Standard inhibitory forgetting effects emerged on both memory tasks but the extent of forgetting across these tasks was not correlated. Furthermore, there was no relationship between memory inhibition tasks and either of the main behavioural inhibition measures. At a time when cognitive inhibition continues to gain acceptance as an explanatory mechanism, our study raises fundamental questions about what we actually know about inhibition and how it is affected by the processing demands of particular inhibitory tasks.