Psychiatry - Research Publications

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    Association of Neural Connectome With Early Experiences of Abuse in Adults.
    Korgaonkar, MS ; Breukelaar, IA ; Felmingham, K ; Williams, LM ; Bryant, RA (American Medical Association (AMA), 2023-01-03)
    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 difference, 0.07; 95% CI, 0.05-0.08; familywise, Bonferroni-corrected P = .01; Cohen d = 0.82) and compared with those who experienced abuse in adolescence (n = 78; mean difference, 0.06; 95% CI, 0.04-0.08]; familywise, Bonferroni-corrected P < .001; Cohen d = 0.68). Connectome alterations were not observed for those who experienced abuse in adolescence. Connectivity of this signature was transdiagnostic and independent of the nature and frequency of abuse, sex, or current symptomatic state. CONCLUSIONS AND RELEVANCE: Findings highlight the associations of exposure to abuse before and during adolescence with the whole-brain functional connectome. The experience of child abuse was found to be associated with physiologic changes in intrinsic connectivity, independent of psychopathology, in a way that may affect functioning of systems responsible for perceptual processing and attention.
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    Changes in neural responses during affective and non-affective tasks and improvement of posttraumatic stress disorder symptoms following trauma-focused psychotherapy
    Korgaonkar, MS ; Felmingham, KL ; Malhi, GS ; Williamson, TH ; Williams, LM ; Bryant, RA (SPRINGERNATURE, 2023-03-09)
    At least one-third posttraumatic stress disorder (PTSD) patients do not respond to trauma-focused psychotherapy (TF-psychotherapy), which is the treatment of choice for PTSD. To clarify the change mechanisms that may be associated with treatment response, this study examined changes in neural activations during affective and non-affective processing that occur with improvement of symptoms after TF-psychotherapy. This study assessed PTSD treatment-seeking patients (n = 27) prior to and after TF-psychotherapy using functional magnetic resonance imaging when they completed three tasks: (a) passive viewing of affective faces, (b) cognitive reappraisal of negative images, and (c) non-affective response inhibition. Patients then underwent 9 sessions of TF-psychotherapy, and were assessed on the Clinician-Administered PTSD Scale following treatment. Changes in neural responses in affect and cognitive processing regions-of-interest for each task were correlated with reduction of PTSD severity from pretreatment to posttreatment in the PTSD cohort. Data from 21 healthy controls was used for comparison. Improvement of symptoms in PTSD were associated with increased activation of left anterior insula, reductions in the left hippocampus and right posterior insula during viewing of supraliminally presented affective images, and reduced connectivity between the left hippocampus with the left amygdala and rostral anterior cingulate. Treatment response was also associated with reduced activation in the left dorsolateral prefrontal cortex during reappraisal of negative images. There were no associations between response and activation change during response inhibition. This pattern of findings indicates that improvement of PTSD symptoms following TF-psychotherapy is associated with changes in affective rather than non-affective processes. These findings accord with prevailing models that TF-psychotherapy promotes engagement and mastery of affective stimuli.Clinical Trials Registration: Trial Registration: Prospectively registered at Australian and New Zealand Clinical Trials Registry, ACTRN12612000185864 and ACTRN12609000324213. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83857.
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    Impact of displacement context on psychological distress in refugees resettled in Australia: a longitudinal population-based study
    Nickerson, A ; Kashyap, S ; Keegan, D ; Edwards, B ; Forrest, W ; Bryant, RA ; O'Donnell, M ; Felmingham, K ; McFarlane, AC ; Tol, WA ; Lenferink, L ; Hoffman, J ; Liddell, BJ (CAMBRIDGE UNIV PRESS, 2022-07-12)
    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.
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    Torture exposure and the functional brain: investigating disruptions to intrinsic network connectivity using resting state fMRI (vol 12, 37, 2022)
    Liddell, BJ ; Das, P ; Malhi, GS ; Felmingham, KL ; Outhred, T ; Cheung, J ; Den, M ; Nickerson, A ; Askovic, M ; Aroche, J ; Coello, M ; Bryant, RA (SPRINGERNATURE, 2022-02-21)
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    Torture exposure and the functional brain: investigating disruptions to intrinsic network connectivity using resting state fMRI
    Liddell, BJ ; Das, P ; Malhi, GS ; Felmingham, KL ; Outhred, T ; Cheung, J ; Den, M ; Nickerson, A ; Askovic, M ; Aroche, J ; Coello, M ; Bryant, RA (SPRINGERNATURE, 2022-01-26)
    Torture has profound psychological and physiological consequences for survivors. While some brain structures and functions appear altered in torture survivors, it is unclear how torture exposure influences functional connectivity within and between core intrinsic brain networks. In this study, 37 torture survivors (TS) and 62 non-torture survivors (NTS) participated in a resting-state fMRI scan. Data-driven independent components analysis identified active intrinsic networks. Group differences in functional connectivity in the default mode network (DMN), salience network (SN) and central executive network (CEN) of the triple network model, as well any prefrontal network, were examined while controlling for PTSD symptoms and exposure to other potentially traumatic events. The analysis identified 25 networks; eight comprised our networks of interest. Within-network group differences were observed in the left CEN (lCEN), where the TS group showed less spectral power in the low-frequency band. Differential internetwork dynamic connectivity patterns were observed, where the TS group showed stronger positive coupling between the lCEN and anterior dorsomedial and ventromedial DMN, and stronger negative coupling between a lateral frontal network and the lCEN and anterior dorsomedial DMN (when contrasted with the NTS group). Group differences were not attributed to torture severity or dissociative symptoms. Torture survivors showed disrupted dynamic functional connectivity between a laterally-aligned lCEN that serves top-down control functions over external processes and the midline DMN that underpins internal self-referential processes, which may be an adaptive response to mitigate the worst effects of the torture experience. This study provides a critical step in mapping the neural signature of torture exposure to guide treatment development and selection.
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    Neural correlates of emotional processing in panic disorder
    Korgaonkar, MS ; Tran, J ; Felmingham, KL ; Williams, LM ; Bryant, RA (ELSEVIER SCI LTD, 2021)
    BACKGROUND: Deficits in emotional processing are conceptualized in prevailing models of anxiety to underpin key symptoms of panic disorder (PD). Neuroimaging studies show evidence of aberrant neural functioning in PD patients during emotional processing, however little is understood about how non-conscious emotional processing impacts neural processes. METHOD: We examined activation and functional connectivity differences in brain regions involved in emotional processing between PD and healthy controls (HC) during subliminal and supraliminal presentations of facial emotions. Twenty-two PD and 33 HC participants were shown happy, sad, neutral, fear, anger and disgust facial expressions during functional magnetic resonance imaging using a 3T MRI scanner. We performed voxelwise ROI analyses at FWE-corrected p < 0.05 for main effects of group and group*emotion interactions. RESULTS: There was less pregenual anterior cingulate cortex (pgACC) activation to subliminal presentations of happy and sad faces in PD compared to HC participants (group*emotion). In addition, PD patients had less pgACC - right amygdala connectivity than HC participants during sad and fear subliminal processing (group*emotion). PD patients also exhibited lower right cerebellum activity across all supraliminal presentations of facial expressions compared to HC. CONCLUSION: These findings suggest that there is aberrant neural processing in PD patients during both conscious and preconscious processing of both positive and negative stimuli, suggesting impaired recruitment of implicit regulatory networks during affective processing. It appears that PD patients may experience deficits in key regulatory connections between inhibitory and emotional neural networks at very early stages of processing of negative affective states.
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    Activating the attachment system modulates neural responses to threat in refugees with PTSD
    Liddell, BJ ; Malhi, GS ; Felmingham, KL ; Den, ML ; Das, P ; Outhred, T ; Nickerson, A ; Askovic, M ; Coello, M ; Aroche, J ; Bryant, RA (OXFORD UNIV PRESS, 2022-12)
    Social attachment systems are disrupted for refugees through trauma and forced displacement. This study tested how the attachment system mitigates neural responses to threat in refugees with posttraumatic stress disorder (PTSD). Refugees with PTSD (N = 28) and refugee trauma-exposed controls (N = 22) viewed threat-related stimuli primed by attachment cues during a functional magnetic resonance imaging scan. Group differences and the moderating effects of avoidant or anxious attachment style and grief related to separation from family on brain activity and connectivity patterns were examined. Separation grief was associated with increased amygdala but decreased ventromedial prefrontal cortical (VMPFC) activity to the attachment prime and decreased VMPFC and hippocampal activity to attachment primed threat in the PTSD (vs trauma-exposed control) group. Avoidant attachment style was connected with increased dorsal frontoparietal attention regional activity to attachment prime cues in the PTSD group. Anxious attachment style was associated with reduced left amygdala connectivity with left medial prefrontal regions to attachment primed threat in the PTSD group. Separation grief appears to reduce attachment buffering of threat reactivity in refugees with PTSD, while avoidant and anxious attachment style modulated attentional and prefrontal regulatory mechanisms in PTSD, respectively. Considering social attachments in refugees could be important to post-trauma recovery, based within changes in key emotion regulation brain systems.
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    Neural activity during response inhibition associated with improvement of dysphoric symptoms of PTSD after trauma-focused psychotherapy-an EEG-fMRI study
    Bryant, RA ; Williamson, T ; Erlinger, M ; Felmingham, KL ; Malhi, G ; Hinton, M ; Williams, L ; Korgaonkar, MS (SPRINGERNATURE, 2021-04-14)
    Although trauma-focused cognitive behavioural therapy (TF-CBT) is the frontline treatment for posttraumatic stress disorder (PTSD), up to one half of patients do not respond optimally to this treatment. Inhibitory functions are important for successful management of PTSD, yet there is a dearth of knowledge regarding the extent to which neural mechanisms unpinning response inhibition are associated with TF-CBT response. Treatment-seeking PTSD patients (n = 40) were assessed during a response inhibition task (the Go/No-Go task) while undergoing functional magnetic imaging (fMRI) and event-related potentials (ERP) in separate sessions. PTSD symptom severity was assessed with the Clinician-Administered PTSD Scale, before undergoing nine sessions of TF-CBT. They were then reassessed post-treatment to estimate reduction in fear and dysphoric symptoms of PTSD. Although neural responses during the inhibitory task did not predict overall symptom change, reduced activation in the left precuneus and the right superior parietal cortex predicted greater improvement in dysphoric symptoms. ERP responses during response inhibition indicated that lower P3 peak latency predicted greater reduction of dysphoric symptoms. There were no significant predictors of changes of fear symptoms. These findings indicate that neural activity associated with response inhibition can act as a predictive biomarker of TF-CBT response for PTSD symptoms. This pattern of findings underscores the importance of delineating the role of biomarkers to predict remission of subtypes of PTSD.
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    White matter anisotropy and response to cognitive behavior therapy for posttraumatic stress disorder
    Korgaonkar, MS ; Felmingham, KL ; Klimova, A ; Erlinger, M ; Williams, LM ; Bryant, RA (SPRINGERNATURE, 2021-01-05)
    Trauma-focused cognitive behavior therapy (TF-CBT) is the gold standard treatment for posttraumatic stress disorder (PTSD), up to one-half of PTSD patients remain treatment non-responders. Although studies have used functional MRI to understand the neurobiology of treatment response, there is less understanding of the role of white matter brain structures in response to TF-CBT. Thirty-six treatment-seeking PTSD patients and 33 age-gender matched healthy controls completed diffusion-weighted imaging scans at baseline. Patients underwent nine sessions of TF-CBT treatment and PTSD symptom severity was assessed with the Clinician-Administered PTSD Scale before and after completing treatment. Patients were assessed to estimate the reduction in overall symptoms and also specifically fear and dysphoric symptoms of PTSD. Tract-based spatial statistical analyses were performed for the PTSD group to evaluate whole-brain correlations of fractional anisotropy (FA) with improvement in overall, fear, and dysphoric symptoms using non-parametric permutation inference testing (pFWE < 0.05). Next, we evaluated if these significant measures also characterized PTSD from controls. Greater improvement in dysphoric symptoms was found correlated with lower FA in white matter regions associated with the limbic system, frontal cortex, thalamic association and projection fibers, corpus callosum, and tracts related to the brainstem. White matter anisotropy was not found associated with either overall or fear symptoms. FA in the significant clusters was similar between PTSD and controls. White-matter related to key functional regions may also play an important role in response to TF-CBT. Our results underscore the heterogeneity of PTSD and the need to evaluate distinct symptom phenotypes in treatment studies.
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    Differential neural predictors of treatment response for fear and dysphoric features of posttraumatic stress disorder
    Bryant, RA ; Erlinger, M ; Felmingham, K ; Malhi, GS ; O'Donnell, ML ; Williams, LM ; Korgaonkar, MS (WILEY, 2020-10)
    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.