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BackgroundCognitive deficits are predictors of functional outcome in patients with psychosis. While conventional antipsychotics are relatively effective on positive symptoms, their impact on negative and cognitive symptoms is limited. Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis. N-acetylcysteine (NAC), a glutathione precursor with glutamatergic properties, has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder, respectively. However, there are few evidence-based approaches for managing cognitive impairment in psychosis. The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder.MethodA sample of 58 participants were randomized in a double fashion to receive 2 g/day of NAC (n = 27) or placebo (n = 31) for 24 weeks. Attention, working memory and executive function domains were assessed. Differences between cognitive performance at baseline and end point were examined using Wilcoxon's test. The Mann–Whitney test was used to examine the differences between the NAC and placebo groups at the end point.ResultsParticipants treated with NAC had significantly higher working memory performance at week 24 compared with placebo (U = 98.5, p = 0.027).ConclusionsNAC may have an impact on cognitive performance in psychosis, as a significant improvement in working memory was observed in the NAC-treated group compared with placebo; however, these preliminary data require replication. Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis. [ABSTRACT FROM PUBLISHER]

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.

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.

Background: Childhood adversity is associated with mental disorder following military deployment. However, it is unclear how different childhood trauma profiles relate to developing a post-deployment disorder. We investigated childhood trauma prospectively in determining new post-deployment probable disorder., Methods: In total, 1009 Regular male ADF personnel from the Australian Defence Force (ADF) Middle East Area of Operations (MEAO) Prospective Study provided pre- and post-deployment self-report data. Logistic regression and generalised structural equation modelling were utilised to examine associations between childhood trauma and new post-deployment probable disorder and possible mediator pathways through pre-deployment symptoms., Results: There were low rates of pre-deployment probable disorder. New post-deployment probable disorder was associated with childhood trauma, index deployment factors (combat role and deployment trauma) and pre-deployment symptoms but not with demographic, service or adult factors prior to the index deployment (including trauma, combat or previous deployment). Even after controlling for demographic, service and adult factors prior to the index deployment as well as index deployment trauma, childhood trauma was still a significant determinant of new post-deployment probable disorder. GSEM demonstrated that the association between interpersonal childhood trauma and new post-deployment probable disorder was fully mediated by pre-deployment symptoms. This was not the case for those who experienced childhood trauma that was not interpersonal in nature., Conclusions: To determine the risk of developing a post-deployment disorder an understanding of the types of childhood trauma encountered is essential, and pre-deployment symptom screening alone is insufficient.

Background: To better understand the associations of childhood trauma and childhood disorder with past-year suicidality (thoughts, plans or attempts), we compared male military and civilian populations aged 18-60 years old., Methods: Data derived from the 2010 Australian Defence Force (ADF) Mental Health Prevalence and Wellbeing Study and the 2007 Australian Bureau of Statistics Australian National Survey of Mental Health and Wellbeing were compared using logistic regression and Generalized Structural Equation Modelling (GSEM)., Results: A greater proportion of the ADF experienced suicidality than civilians. Those who experienced childhood trauma that was not interpersonal in nature were not at increased odds of suicidality, in either population. A higher proportion of the ADF experienced three or more types of trauma in childhood and first experienced three or more types of trauma in adulthood. Both were associated with suicidality in the ADF and civilians. Childhood anxiety had a strong and independent association with suicidality in the ADF (controlling for demographics and childhood trauma, adult trauma and adult onset disorder). Childhood anxiety fully mediated the relationship between childhood trauma and suicidality in the ADF, but not in civilians., Conclusions: These data highlight the need to take a whole life approach to understanding suicidality, and the importance of categorizing the nature of childhood trauma exposure. Importantly, childhood anxiety was not only associated with suicidality, it fully mediated the relationship between childhood trauma and suicidality in the more trauma exposed (military) population only. These findings have the potential to inform the development of strategies for suicide prevention.