Psychiatry - Research Publications

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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, 2020-06-24)
    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.
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    Intrusive Memories of Distressing Information: An fMRI Study
    Battaglini, E ; Liddell, B ; Das, P ; Malhi, G ; Felmingham, K ; Bryant, RA ; Stamatakis, EA (PUBLIC LIBRARY SCIENCE, 2016-09-29)
    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.
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    Dysregulation in cortical reactivity to emotional faces in PTSD patients with high dissociation symptoms
    Klimova, A ; Bryant, RA ; Williams, LM ; Felmingham, KL (TAYLOR & FRANCIS LTD, 2013-01-01)
    BACKGROUND: Predominant dissociation in posttraumatic stress disorder (PTSD) is characterized by restricted affective responses to positive stimuli. To date, no studies have examined neural responses to a range of emotional expressions in PTSD with high dissociative symptoms. OBJECTIVE: This study tested the hypothesis that PTSD patients with high dissociative symptoms will display increased event-related potential (ERP) amplitudes in early components (N1, P1) to threatening faces (angry, fearful), and reduced later ERP amplitudes (Vertex Positive Potential (VPP), P3) to happy faces compared to PTSD patients with low dissociative symptoms. METHODS: Thirty-nine civilians with PTSD were classified as high dissociative (n=16) or low dissociative (n=23) according to their responses on the Clinician Administered Dissociative States Scale. ERPs were recorded, whilst participants viewed emotional (happy, angry, fear) and neutral facial expressions in a passive viewing task. RESULTS: High dissociative PTSD patients displayed significantly increased N120 amplitude to the majority of facial expressions (neutral, happy, and angry) compared to low dissociative PTSD patients under conscious and preconscious conditions. The high dissociative PTSD group had significantly reduced VPP amplitude to happy faces in the conscious condition. CONCLUSION: High dissociative PTSD patients displayed increased early (preconscious) cortical responses to emotional stimuli, and specific reductions to happy facial expressions in later (conscious), face-specific components compared to low dissociative PTSD patients. Dissociation in PTSD may act to increase initial pre-attentive processing of affective stimuli, and specifically reduce cortical reactivity to happy faces when consciously processing these stimuli.
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    The Roles of Noradrenergic and Glucocorticoid Activation in the Development of Intrusive Memories
    Bryant, RA ; McGrath, C ; Felmingham, KL ; Schmidt, U (PUBLIC LIBRARY SCIENCE, 2013-04-29)
    Intrusive memories are a common feature of many psychological disorders. Recent evidence has potentially extended cognitive models of intrusions by identifying the role of biological markers of arousal at the time of consolidation in subsequent memory for emotional events. This study investigated the role of arousal during consolidation in the development of intrusive memories. Seventy-eight university students (37 men and 41 women) viewed 20 negative and 20 neutral images. Half the participants then underwent a cold pressor test (High Stress), immersing their hand in ice water, while the remaining participants immersed their hand in warm water (Low Stress). Samples of salivary alpha-amylase (sAA) and cortisol were collected from participants at baseline and following the stressor challenge. Participants completed a delayed free recall test and intrusion questionnaires two days later. Participants in the High Stress condition reported more intrusions of negative images than participants in the Low Stress condition. An interaction variable in a linear regression of increased noradrenergic and cortisol values predicted intrusive memories of emotional stimuli for men but not women. These findings are consistent with recent evidence of the combined effects of noradrenaline and corticoid responses to stress on emotional memories, and also with increasing evidence of gender differences in how stress hormones influence formation of emotional memories. These findings point to possible mechanisms by which development of intrusions may be prevented after consolidation of traumatic experiences.
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    The functional epistasis of 5-HTTLPR and BDNF Val66Met on emotion processing: a preliminary study
    Outhred, T ; Das, P ; Dobson-Stone, C ; Griffiths, K ; Felmingham, KL ; Bryant, RA ; Malhi, G ; Kemp, AH (JOHN WILEY & SONS INC, 2012-11-01)
    An epistatic interaction of 5-HTTLPR and BDNF Val66Met polymorphisms has been implicated in the structure of rostral anterior cingulate cortex (rACC) and amygdala (AMY): key regions associated with emotion processing. However, a functional epistasis of 5-HTTLPR and BDNF Val66Met on overt emotion processing has yet to be determined. Twenty-eight healthy, Caucasian female participants provided saliva samples for genotyping and underwent functional magnetic resonance imaging (fMRI) during which an emotion processing protocol were presented. Confirming the validity of this protocol, we observed blood oxygen level-dependent (BOLD) activity consistent with fMRI meta-analyses on emotion processing. Region-of-interest analysis of the rACC and AMY revealed main effects of 5-HTTLPR and BDNF Val66Met, and an interaction of 5-HTTLPR and BDNF Val66Met. The effect of the BDNF Met66 allele was dependent on 5-HTTLPR alleles, such that participants with S and Met alleles had the greatest rACC and AMY activation during the presentation of emotional images relative to other genetic groupings. Increased activity in these regions was interpreted as increased reactivity to emotional stimuli, suggesting that those with S and Met alleles are more reactive to emotional stimuli relative to other groups. Although limited by a small sample, this study contributes novel and preliminary findings relating to a functional epistasis of the 5-HTTLPR and BDNF Val66Met genes in emotion processing and provides guidance on appropriate methods to determine genetic epistasis in fMRI.
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    Reduced Amygdala and Ventral Striatal Activity to Happy Faces in PTSD Is Associated with Emotional Numbing
    Felmingham, KL ; Falconer, EM ; Williams, L ; Kemp, AH ; Allen, A ; Peduto, A ; Bryant, RA ; Hampson, M (PUBLIC LIBRARY SCIENCE, 2014-09-03)
    There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1) individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2) that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral) faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.
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    Prolonged grief in refugees, parenting behaviour and children's mental health
    Bryant, RA ; Edwards, B ; Creamer, M ; O'Donnell, M ; Forbes, D ; Felmingham, KL ; Silove, D ; Steel, Z ; McFarlane, AC ; Van Hooff, M ; Nickerson, A ; Hadzi-Pavlovic, D (SAGE PUBLICATIONS LTD, 2020-10-30)
    BACKGROUND: Many refugees experience bereavement, and as a result they suffer elevated rates of prolonged grief disorder. Evidence also indicates that elevated rates of psychological disturbance in refugee children can be associated with parental mental health. This study examined the extent to which prolonged grief disorder in refugees is associated with their parenting behaviour and in turn with their children's mental health. METHODS: This study recruited participants from the Building a New Life in Australia prospective cohort study of refugees admitted to Australia between October 2013 and February 2014. The current data were collected in 2015-2016 and comprised 1799 adults, as well as 411 children of the adult respondents. Adult refugees were assessed for trauma history, post-migration difficulties, harsh and warm parenting, probable prolonged grief disorder and posttraumatic stress disorder. Children were administered the Strengths and Difficulties Questionnaire. The current analyses on bereaved refugees comprise 110 caregivers and 178 children. RESULTS: In this cohort, 37% of bereaved refugees reported probable prolonged grief disorder. Path analysis indicated that caregivers' grief was directly associated with children's emotional difficulties. Caregiver warmth was associated with reduced emotional problems in children of refugees with minimal grief but associated with more emotional problems in caregivers with more severe grief. More harsh parenting was associated with children's conduct problems, and this was more evident in those with less severe grief. CONCLUSION: Severity of prolonged grief disorder is directly linked to refugee children's mental health. The association between parenting style, grief severity and children's mental health highlights that managing grief reactions in refugees can benefit both refugees and their children.
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    The contribution of gender-based violence and network trauma to gender differences in Post-Traumatic Stress Disorder
    Silove, D ; Baker, JR ; Mohsin, M ; Teesson, M ; Creamer, M ; O'Donnell, M ; Forbes, D ; Carragher, N ; Slade, T ; Mills, K ; Bryant, R ; McFarlane, A ; Steel, Z ; Felmingham, K ; Rees, S ; Homberg, J (PUBLIC LIBRARY SCIENCE, 2017-02-16)
    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.
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    Self-Orientation Modulates the Neural Correlates of Global and Local Processing
    Liddell, BJ ; Das, P ; Battaglini, E ; Malhi, GS ; Felmingham, KL ; Whitford, TJ ; Bryant, RA ; Antal, A (PUBLIC LIBRARY SCIENCE, 2015-08-13)
    Differences in self-orientation (or "self-construal") may affect how the visual environment is attended, but the neural and cultural mechanisms that drive this remain unclear. Behavioral studies have demonstrated that people from Western backgrounds with predominant individualistic values are perceptually biased towards local-level information; whereas people from non-Western backgrounds that support collectivist values are preferentially focused on contextual and global-level information. In this study, we compared two groups differing in predominant individualistic (N = 15) vs collectivistic (N = 15) self-orientation. Participants completed a global/local perceptual conflict task whilst undergoing functional Magnetic Resonance Imaging (fMRI) scanning. When participants high in individualistic values attended to the global level (ignoring the local level), greater activity was observed in the frontoparietal and cingulo-opercular networks that underpin attentional control, compared to the match (congruent) baseline. Participants high in collectivistic values activated similar attentional control networks o only when directly compared with global processing. This suggests that global interference was stronger than local interference in the conflict task in the collectivistic group. Both groups showed increased activity in dorsolateral prefrontal regions involved in resolving perceptual conflict during heightened distractor interference. The findings suggest that self-orientation may play an important role in driving attention networks to facilitate interaction with the visual environment.
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    Association of FKBP5 polymorphisms and resting-state activity in a frontotemporal-parietal network
    Bryant, RA ; Felmingham, KL ; Liddell, B ; Das, P ; Malhi, GS (NATURE PUBLISHING GROUP, 2016-10-18)
    The FKBP5 polymorphism is a key regulator of the glucocorticoid system underpinning stress responsivity, and risk alleles can increase vulnerability for developing posttraumatic stress disorder. To delineate the specific role of FKBP5 risk alleles unencumbered by the confounds of psychopathology, this study investigated whether high-risk alleles of the FKBP5 polymorphism are characterized by distinctive neural activity during resting state. Thirty-seven healthy participants were selected on the basis of four SNPs in the FKBP5 gene region (rs3800373, rs9296158, rs1360780 and rs9470080) to determine participants who were carriers of the FKBP5 high- and low-risk alleles. Spatial maps, power spectra and connectivity in neural networks active during resting state were assessed with functional magnetic resonance imaging (fMRI). During resting-state fMRI, FKBP5 low-risk allele group displayed more power in the low frequency range (<0.1 Hz) than the high-risk allele group, who had significantly more power in higher frequency bins (>0.15 Hz). This difference was apparent only in a frontotemporoparietal network underpinning salience detection and emotion processing. This study provides initial evidence that the risk alleles of the FKBP5 polymorphism are associated with different resting-state activity in a frontotemporal-parietal network, and may point to mechanisms underpinning high-risk carriers' vulnerability to severe stress reactions.