Interactive relationship between alexithymia, psychological distress and posttraumatic stress disorder symptomology across time.

Alexithymia, psychological distress, and posttraumatic stress disorder (PTSD) are highly related constructs. The ongoing debate about the nature and relationship between these constructs is perpetuated by an overreliance on cross-sectional research. We examined the longitudinal interactive relationship between alexithymia, psychological distress, and PTSD. We hypothesised that there is an interactive relationship between the three constructs. Military personnel (N = 1871) completed the Toronto Alexithymia Scale, the Kessler 10 and a PTSD Checklist (PCL-C) at pre-deployment, post-deployment, and at 3-4 years following the post-deployment assessment. We initially tested whether psychological distress is either a moderator or mediator in the relationship between alexithymia and PTSD across the time points. General psychological distress was a partial mediator of total PTSD severity and hyperarousal symptomology at all three time points. Psychological distress fully mediated re-experiencing and avoidance symptomology at all three time points. Our results suggest that those with alexithymia are at longitudinal risk of developing more severe PTSD symptomology and experiencing hyperarousal irrespective of temporal proximity to traumatic exposure. Further, vulnerability to the emergence of re-experiencing and avoidance symptomology for those with alexithymia is increased when one experiences greater distress. Our results show that alexithymia is a persistent risk factor for PTSD symptomology.

Cortico-Striatal Activity Characterizes Human Safety Learning via Pavlovian Conditioned Inhibition.

Safety learning generates associative links between neutral stimuli and the absence of threat, promoting the inhibition of fear and security-seeking behaviors. Precisely how safety learning is mediated at the level of underlying brain systems, particularly in humans, remains unclear. Here, we integrated a novel Pavlovian conditioned inhibition task with ultra-high field (7 Tesla) fMRI to examine the neural basis of safety learning in 49 healthy participants. In our task, participants were conditioned to two safety signals: a conditioned inhibitor that predicted threat omission when paired with a known threat signal (A+/AX-), and a standard safety signal that generally predicted threat omission (BC-). Both safety signals evoked equivalent autonomic and subjective learning responses but diverged strongly in terms of underlying brain activation (PFDR whole-brain corrected). The conditioned inhibitor was characterized by more prominent activation of the dorsal striatum, anterior insular, and dorsolateral PFC compared with the standard safety signal, whereas the latter evoked greater activation of the ventromedial PFC, posterior cingulate, and hippocampus, among other regions. Further analyses of the conditioned inhibitor indicated that its initial learning was characterized by consistent engagement of dorsal striatal, midbrain, thalamic, premotor, and prefrontal subregions. These findings suggest that safety learning via conditioned inhibition involves a distributed cortico-striatal circuitry, separable from broader cortical regions involved with processing standard safety signals (e.g., CS-). This cortico-striatal system could represent a novel neural substrate of safety learning, underlying the initial generation of "stimulus-safety" associations, distinct from wider cortical correlates of safety processing, which facilitate the behavioral outcomes of learning.SIGNIFICANCE STATEMENT Identifying safety is critical for maintaining adaptive levels of anxiety, but the neural mechanisms of human safety learning remain unclear. Using 7 Tesla fMRI, we compared learning-related brain activity for a conditioned inhibitor, which actively predicted threat omission, and a standard safety signal (CS-), which was passively unpaired with threat. The inhibitor engaged an extended circuitry primarily featuring the dorsal striatum, along with thalamic, midbrain, and premotor/PFC regions. The CS- exclusively involved cortical safety-related regions observed in basic safety conditioning, such as the vmPFC. These findings extend current models to include learning-specific mechanisms for encoding stimulus-safety associations, which might be distinguished from expression-related cortical mechanisms. These insights may suggest novel avenues for targeting dysfunctional safety learning in psychopathology.

Subcortical contributions to salience network functioning during negative emotional processing.

Core regions of the salience network (SN), including the anterior insula (aINS) and dorsal anterior cingulate cortex (dACC), coordinate rapid adaptive changes in attentional and autonomic processes in response to negative emotional events. In doing so, the SN incorporates bottom-up signals from subcortical brain regions, such as the amygdala and periaqueductal gray (PAG). However, the precise influence of these subcortical regions is not well understood. Using ultra-high field 7-Tesla functional magnetic resonance imaging, this study investigated the bottom-up interactions of the amygdala and PAG with the SN during negative emotional salience processing. Thirty-seven healthy participants completed an emotional oddball paradigm designed to elicit a salient negative emotional response via the presentation of random, task-irrelevant negative emotional images. Negative emotional processing was associated with prominent activation in the SN, spanning the amygdala, PAG, aINS, and dACC. Consistent with previous research, analysis using dynamic causal modelling revealed an excitatory influence from the amygdala to the aINS, dACC, and PAG. In contrast, the PAG showed an inhibitory influence on amygdala, aINS and dACC activity. Our findings suggest that the amygdala may amplify the processing of negative emotional stimuli in the SN to enable upstream access to attentional resources. In comparison, the inhibitory influence of the PAG possibly reflects its involvement in modulating sympathetic-parasympathetic autonomic arousal mediated by the SN. This PAG-mediated effect may be driven by amygdala input and facilitate bottom-up processing of negative emotional stimuli. Overall, our results show that the amygdala and PAG modulate divergent functions of the SN during negative emotional processing.

Emotion response disconcordance among trauma-exposed adults: the impact of alexithymia.

BACKGROUND: Emotion processing deficits have been identified as a critical transdiagnostic factor that facilitates distress after trauma exposure. Limited skills in identifying and labelling emotional states (i.e. alexithymia) may present on the more automated (less conscious) end of the spectrum of emotional awareness and clarity. Individuals with alexithymia tend to exhibit a disconcordance between subjective experience and autonomic activity (e.g. where high levels of subjective emotional intensity are associated with low physiological arousal), which may exacerbate distress. Although there is a robust link between alexithymia and trauma exposure, no work to date has explored whether alexithymia is associated with emotional response disconcordance among trauma-exposed adults. METHOD: Using a validated trauma script paradigm, the present study explored the impact of alexithymia on emotion response concordance [skin conductance (Galvanic Skin Response, GSR) and Total Mood Disturbance (TMD)] among 74 trauma-exposed adults recruited via a posttraumatic stress disorder (PTSD) treatment clinic and student research programme. RESULTS: Unlike posttraumatic symptom severity, age, sex, participant type and mood (which showed no effect on emotion response concordance), alexithymia was associated with heightened emotion response disconcordance between GSR and TMD [F(1, 37) = 8.93, p = 0.006], with low GSR being associated with high TMD. Observed effects of the trauma script were entirely accounted for by the interaction with alexithymia, such that those with alexithymia showed a negligible association between subjective and physiological states. CONCLUSION: This finding is paramount as it shows that a large proportion of trauma-exposed adults have a divergent emotion engagement profile.

Neural predictors of cognitive-behavior therapy outcome in anxiety-related disorders: a meta-analysis of task-based fMRI studies.

BACKGROUND: Cognitive-behavior therapy (CBT) is a well-established first-line intervention for anxiety-related disorders, including specific phobia, social anxiety disorder, panic disorder/agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. Several neural predictors of CBT outcome for anxiety-related disorders have been proposed, but previous results are inconsistent. METHODS: We conducted a systematic review and meta-analysis of task-based functional magnetic resonance imaging (fMRI) studies investigating whole-brain predictors of CBT outcome in anxiety-related disorders (17 studies, n = 442). RESULTS: Across different tasks, we observed that brain response in a network of regions involved in salience and interoception processing, encompassing fronto-insular (the right inferior frontal gyrus-anterior insular cortex) and fronto-limbic (the dorsomedial prefrontal cortex-dorsal anterior cingulate cortex) cortices was strongly associated with a positive CBT outcome. CONCLUSIONS: Our results suggest that there are robust neural predictors of CBT outcome in anxiety-related disorders that may eventually lead (probably in combination with other data) to develop personalized approaches for the treatment of these mental disorders.

A thalamo-centric neural signature for restructuring negative self-beliefs.

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.

Characterisation of Deficits and Sex Differences in Verbal and Visual Memory/Learning in Bipolar Disorder.

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.

Posttraumatic Stress and Alexithymia: Symptom Associations.

ABSTRACT: There is a demonstrated association between alexithymia and posttraumatic stress disorder (PTSD). However, work has largely focused on male-dominant, high-risk occupation populations. We aimed to explore the relationship between posttraumatic stress (PTS) and alexithymia among 100 trauma-exposed female university students. Participants completed a Life Events Checklist, the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), and the Toronto Alexithymia Scale (TAS-20). Multiple regressions were run to examine whether alexithymia was associated with each of the PCL-5 subscales. The TAS-20 total scores were associated with total PTS scores, ß = 0.47, t(99) = 5.22, p < 0.001. On a subscale level, Difficulty in Identifying Feelings (DIF) was positively associated (ß = 0.50 to 0.41) with all PCL-5 subscales except for Avoidance. Our results align with research showing that for women, the DIF subscale is most strongly associated with PTS, in contrast with the literature on male samples, showing strongest associations with the Difficulties in Describing Feelings subscale, suggesting sex differences in associations between PTS and alexithymia. Our study supports the universality of the associations between alexithymia and PTS.

Principles for delivering improved care of people with functional seizures: Closing the treatment gap.

Patients diagnosed with functional (psychogenic nonepileptic) seizures have similar or greater levels of disability, morbidity and mortality than people with epilepsy, but there are far fewer treatment services. In contrast to epilepsy, the current understanding of pathophysiological mechanisms and the development of evidence-based treatments for functional seizures is rudimentary. This leads to high direct healthcare costs and high indirect costs to the patient, family and wider society. There are many patient, clinician and system-level barriers to improving outcomes for functional seizures. At a patient level, these include the heterogeneity of symptoms, diagnostic uncertainty, family factors and difficulty in perceiving psychological aspects of illness and potential benefits of treatment. Clinician-level barriers include sub-specialism, poor knowledge, skills and attitudes and stigma. System-level barriers include the siloed nature of healthcare, the high prevalence of functional seizures and funding models relying on individual medical practitioners. Through the examination of international examples and expert recommendations, several themes emerge that may address some of these barriers. These include (1) stepped care with low-level, brief generalised interventions, proceeding to higher level, extended and individualised treatments; (2) active triage of complexity, acuity and treatment readiness; (3) integrated interdisciplinary teams that individualise formulation, triage, and treatment planning and (4) shared care with primary, emergency and community providers and secondary consultation. Consideration of the application of these principles to the Australian and New Zealand context is proposed as a significant opportunity to meet an urgent need.

Dynamic Neural Interactions Supporting the Cognitive Reappraisal of Emotion.

The cognitive reappraisal of emotion is hypothesized to involve frontal regions modulating the activity of subcortical regions such as the amygdala. However, the pathways by which structurally disparate frontal regions interact with the amygdala remains unclear. In this study, 104 healthy young people completed a cognitive reappraisal task. Dynamic causal modeling (DCM) was used to map functional interactions within a frontoamygdalar network engaged during emotion regulation. Five regions were identified to form the network: the amygdala, the presupplementary motor area (preSMA), the ventrolateral prefrontal cortex (vlPFC), dorsolateral prefrontal cortex (dlPFC), and ventromedial prefrontal cortex (vmPFC). Bayesian Model Selection was used to compare 256 candidate models, with our winning model featuring modulations of vmPFC-to-amygdala and amygdala-to-preSMA pathways during reappraisal. Moreover, the strength of amygdala-to-preSMA modulation was associated with the habitual use of cognitive reappraisal. Our findings support the vmPFC serving as the primary conduit through which prefrontal regions directly modulate amygdala activity, with amygdala-to-preSMA connectivity potentially acting to shape ongoing affective motor responses. We propose that these two frontoamygdalar pathways constitute a recursive feedback loop, which computes the effectiveness of emotion-regulatory actions and drives model-based behavior.

Timing matters: Transcranial direct current stimulation after extinction learning impairs subsequent fear extinction retention.

BACKGROUND: Transcranial direct current stimulation (tDCS) has previously been shown to improve fear extinction learning and retention when administered prior to or during extinction learning. This study investigates whether tDCS immediately following extinction learning improves efficacy of extinction memory retention. METHODS: 30 participants completed a 2-day fear learning and extinction paradigm, where they acquired fear of a stimulus conditioned to an aversive electric shock on day 1. Extinction learning occurred on day 1, with tDCS or sham tDCS administered immediately following the learning phase. Participants returned for a second day test of extinction memory recall. Skin conductance was measured as the primary outcome. RESULTS/CONCLUSIONS: Participants in the tDCS group showed impaired fear extinction retention on day 2, marked by significant generalisation of fear to the safety stimulus. This contrasts with earlier studies showing improved extinction retention when stimulation occurred during encoding of extinction learning, compared to immediate consolidation as in our study. These findings may have important implications for the use of tDCS during exposure therapy for anxiety and trauma disorders.

The distinctive neural circuitry of complex posttraumatic stress disorder during threat processing.

BACKGROUND: There is controversy over the extent to which the new International Classification of Diseases (ICD-11) diagnosis of complex posttraumatic stress disorder (CPTSD) is distinct from posttraumatic stress disorder (PTSD). This study aimed to conduct the first investigation of distinctive neural processes during threat processing in CPTSD relative to PTSD. METHOD: This cross-sectional functional magnetic resonance study included 99 participants who met criteria for PTSD (PTSD = 32, CPTSD = 28) and 39 trauma-exposed controls. PTSD was assessed with the Clinician-Administered PTSD Scale (CAPS). CPTSD was assessed with an adapted version of the International Trauma Questionnaire. Neural responses were measured across the brain while threat or neutral faces were presented at both supraliminal and subliminal levels. RESULTS: During supraliminal presentations of threat stimuli, there was greater bilateral insula and right amygdala activation in CPTSD participants relative to PTSD. Reduced supraliminal right dorsolateral prefrontal cortex activation and increased subliminal amygdala and insula activation were observed as common dysfunction for both CPTSD and PTSD groups relative to trauma controls. There were no significant differences in terms of subliminal presentations and no differences in functional connectivity. Dissociative responses were positively associated with right insula activation (r = 0.347, p < 0.01). CONCLUSIONS: These results provide the first evidence of distinct neural profiles of CPTSD and PTSD during threat processing. The observation of increased insula and right amygdala activation in CPTSD accords with the proposal that CPTSD is distinguished from PTSD by disturbances in emotion regulation and self-concept.

Reappraisal-related neural predictors of treatment response to cognitive behavior therapy for post-traumatic stress disorder.

BACKGROUND: Although trauma-focused cognitive behavior therapy (TF-CBT) is the frontline treatment for post-traumatic stress disorder (PTSD), one-third of patients are treatment non-responders. To identify neural markers of treatment response to TF-CBT when participants are reappraising aversive material. METHODS: This study assessed PTSD patients (n = 37) prior to TF-CBT during functional magnetic brain resonance imaging (fMRI) when they reappraised or watched traumatic images. Patients then underwent nine sessions of TF-CBT, and were then assessed for symptom severity on the Clinician-Administered PTSD Scale. FMRI responses for cognitive reappraisal and emotional reactivity contrasts of traumatic images were correlated with the reduction of PTSD severity from pretreatment to post-treatment. RESULTS: Symptom improvement was associated with decreased activation of the left amygdala during reappraisal, but increased activation of bilateral amygdala and hippocampus during emotional reactivity prior to treatment. Lower connectivity of the left amygdala to the subgenual anterior cingulate cortex, pregenual anterior cingulate cortex, and right insula, and that between the left hippocampus and right amygdala were also associated with symptom improvement. CONCLUSIONS: These findings provide evidence that optimal treatment response to TF-CBT involves the capacity to engage emotional networks during emotional processing, and also to reduce the engagement of these networks when down-regulating emotions.

Cannabinoid polymorphisms interact with plasma endocannabinoid levels to predict fear extinction learning.

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.

Prolonged grief in refugees, parenting behaviour and children's mental health.

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.

The impact of torture on interpersonal threat and reward neurocircuitry.

OBJECTIVE: Torture adversely influences emotional functioning, but the neurophysiological mechanisms underpinning its impact are unknown. This study examined how torture exposure affects the neural substrates of interpersonal threat and reward processing. METHODS: Male refugees with (N = 31) and without (N = 27) torture exposure completed a clinical interview and functional magnetic resonance imaging scan where they viewed fear, happy and neutral faces. Between-group activations and neural coupling were examined as moderated by posttraumatic stress disorder symptom severity and cumulative trauma load. RESULTS: Posttraumatic stress disorder symptom severity and trauma load significantly moderated group differences in brain activation and connectivity patterns. Torture survivors deactivated the ventral striatum during happy processing compared to non-torture survivor controls as a function of increased posttraumatic stress disorder symptom severity - particularly avoidance symptoms. The ventral striatum was more strongly coupled with the inferior frontal gyrus in torture survivors. Torture survivors also showed left hippocampal deactivation to both fear and happy faces, moderated by trauma load, compared to controls. Stronger coupling between the hippocampus and frontal, temporoparietal and subcortical regions during fear processing was observed, with pathways being predicted by avoidance and hyperarousal symptoms. CONCLUSION: Torture exposure was associated with distinct brain activity and connectivity patterns during threat and reward processing, dependent on trauma exposure and posttraumatic stress disorder symptom severity. Torture appears to affect emotional brain functioning, and findings have the potential to guide more targeted interventions for torture survivors.

A Pilot Study of the Efficacy of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Treating Posttraumatic Psychopathology: A Randomized Controlled Trial.

The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is an intervention that targets common mechanisms that maintain symptoms across multiple disorders. The UP has been shown to be effective across many disorders, including generalized anxiety disorder, major depressive episode (MDE), and panic disorder, that commonly codevelop following trauma exposure. The present study represented the first randomized controlled trial of the UP in the treatment of trauma-related psychopathology, including posttraumatic stress disorder (PTSD), depression, and anxiety symptoms. Adults (N = 43) who developed posttraumatic psychopathology that included PTSD, MDE, or an anxiety disorder after sustaining a severe injury were randomly assigned to receive 10-14 weekly, 60-min sessions of UP (n = 22) or usual care (n = 21). The primary treatment outcome was PTSD symptom severity, with secondary outcomes of depression and anxiety symptom severity and loss of diagnosis for any trauma-related psychiatric disorder. Assessments were conducted at intake, posttreatment, and 6-month follow-up. Posttreatment, participants who received the UP showed significantly larger reductions in PTSD, Hedges' g = 1.27; anxiety, Hedges' g = 1.20; and depression symptom severity, Hedges' g = 1.40, compared to those receiving usual care. These treatment effects were maintained at 6-month follow-up for PTSD, anxiety, and depressive symptom severity. Statistically significant posttreatment loss of PTSD, MDE, and agoraphobia diagnoses was observed for participants who received the UP but not usual care. This study provides preliminary evidence that the UP may be an effective non-trauma-focused treatment for PTSD and other trauma-related psychopathology.

The Effect of Self-Reported REM Behavior Disorder Symptomology on Intrusive Memories in Post-Traumatic Stress Disorder.

Background: PTSD is characterised by severe sleep disturbances, which is increasingly recognised to in many cases consist of similar symptomology to sleep disorders such as REM Behaviour Disorder (RBD). The present study aimed to investigate whether different aspects of sleep quality influence intrusive memory development and whether PTSD status moderates this relationship. Participants and Methods: 34 PTSD, 52 trauma-exposed (TE) and 42 non-trauma exposed (NTE) participants completed an emotional memory task, where they viewed 60 images (20 positive, 20 negative and 20 neutral) and, two days later, reported how many intrusive memories they had of each valence category. Participants also completed three measures of sleep quality: the Pittsburgh Sleep Quality Index, the REM Behaviour Disorder Screening Questionnaire and total hours slept before each session. Results: The PTSD group reported poorer sleep quality than both TE and NTE groups on all three measures, and significantly more negative intrusive memories than the NTE group. Mediation analyses revealed that self-reported RBD symptomology before the second session mediated the relationship between PTSD status and intrusive memories. Follow-up moderation analyses revealed that self-reported RBD symptomology before the second session was only a significant predictor of intrusion in the PTSD group, though with a small effect size. Conclusions: These findings suggest that RBD symptomology is an indicator of consolidation of intrusive memories in PTSD but not trauma-exposed or healthy participants, which supports the relevance of characterising RBD in PTSD.

Brain-derived neurotropic factor and cortisol levels negatively predict working memory performance in healthy males.

There is now significant literature suggesting that increasing brain-derived neurotropic factor (BDNF) signalling may improve memory-related disorders such as Alzheimer's disease. However, the effects of BDNF on short-term and working memory are not clear and existing evidence is inconsistent. Here we measured plasma BDNF and salivary cortisol levels, as well as working memory, on an N-Back task before and after mixed psychosocial/physiological stress induction in healthy males (N = 29). Stress induction was associated with higher circulating cortisol, but not BDNF levels. Higher cortisol and BDNF levels were significantly associated with poorer accuracy before and after stress induction. There was also a significant interaction, such that higher BDNF was associated with a buffering effect on the negative association between high cortisol and working memory. Future studies should replicate this data in larger samples, with emphasis on cortisol/BDNF interactions in determining working memory performance.

Reproducibility of saliva progesterone measured by immunoassay compared to liquid chromatography mass spectrometry.

Immunoassay overestimates progesterone in blood, but no studies have tested whether this occurs in saliva. We measured progesterone in saliva using immunoassay and mass spectrometry. We tested the immunoassay for cross reactivity with dehydroepiandrosterone sulfate (DHEA-S) and 17α-hydroxyprogesterone (17α-OHP). Progesterone was significantly higher in immunoassay compared to mass spectrometry. Immunoassay progesterone levels increased in when incremental levels of 17α-OHP standard was added. This effect was not observed with the addition of DHEA-S. Research using salivary progesterone immunoassay techniques should be wary, particularly with individuals taking steroid supplementation or with high levels of progesterone metabolites.