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Post-traumatic stress disorder (PTSD) is unique among psychiatric disorders in that the cause, a traumatic event (or events), is known. PTSD is often the subject of legal proceedings, with persons seeking compensation from the agency considered responsible for the trauma. While PTSD is clearly a psychiatric disorder, there is less agreement about whether PTSD can also be categorised as a bodily injury, as defined by the Montreal Convention 1999. This article describes Pel-Air Pty Ltd v Casey, a case involving physical and psychiatric injuries resulting from the forced landing of a plane. It was ruled that PTSD was not a bodily injury under the Convention. While psychiatric expert evidence demonstrated that PTSD causes neurochemical changes, it was ruled that neurochemical changes do not indicate a bodily injury. We describe evidence of neuroanatomical changes and neurochemical changes in PTSD, proposing that the structure of the brain in PTSD support the argument that PTSD is a bodily injury.

This systematic review was conducted to develop a broader understanding of the characteristics of older people who commit homicide. PubMed, Embase and PsycINFO were searched on 28 November 2018 for studies on homicides committed by people aged 55 years and over. Only articles published in English were included. Studies focusing on euthanasia and palliation were excluded. Fifteen articles met the inclusion criteria, with studies from the United States (n = 6), United Kingdom (n = 2), Australia, Canada, Finland, Italy, New Zealand, Switzerland and Turkey. The age range for ‘older offenders’ varied across the studies. Some studies examined the phenomena of sexual homicide and homicide-suicide. Offenders were more likely to be male, and the domestic setting for the offence was common. Social maladjustment, a care-giver role, personal physical and mental health problems and/or substance misuse issues were relevant to the offenders. Firearms-related homicides were common. Homicide committed by older people is rare but there may be a constellation of risk factors specific to this age group that needs further understanding. Our findings suggest that there is an increasing need for care of older offenders and a need for specialist forensic services for elderly offenders.

Background and Hypothesis Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet a significant proportion of individuals on clozapine continue to experience disabling symptoms, despite being treated with an adequate dose. There is a need for adjunct treatments to augment clozapine, notably for negative and cognitive symptoms. One such potential agent is the glutathione precursor N-acetylcysteine (NAC). Study Design A randomized double-blind, multi-center, placebo-controlled trial for clozapine patients with enduring psychotic symptoms (n = 84) was undertaken to investigate the efficacy of adjunctive NAC (2 g daily) for negative symptoms, cognition and quality of life (QoL). Efficacy was assessed at 8, 24, and 52 weeks. Study Results NAC did not significantly improve negative symptoms (P = .62), overall cognition (P = .71) or quality of life (Manchester quality of life: P = .11; Assessment of quality of life: P = .57) at any time point over a 1-year period of treatment. There were no differences in reported side effects between the groups (P = .26). Conclusions NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with “Australian and New Zealand Clinical Trials” on the 30 May, 2016 (Registration Number: ACTRN12615001273572).

Increased cytokines and increased intercellular adhesion molecule-1 (ICAM1) found in the schizophrenia prefrontal cortex and in the blood may relate to cognitive deficits. Endothelial ICAM1 regulates immune cell trafficking into the brain by binding to integrins located on the surface of leukocytes. Whether the circulating levels of the main ICAM1 adhesion partners, lymphocyte-function associated antigen-1 (LFA1) and complement receptor 3 (CR3), both integrins, are altered in schizophrenia is unknown. Gene expressions of ICAM1, LFA1 and CR3 were measured in leukocytes from 86 schizophrenia patients and 77 controls. Participants were also administered cognitive testing to determine the extent to which cognitive ability was related to molecular measures of leukocyte adhesion. This cohort was previously stratified into inflammatory subgroups based on circulating cytokine mRNAs; thus, gene expressions were analysed by diagnosis and by inflammatory subgroups. Previously measured plasma ICAM1 protein was elevated in "high inflammation" schizophrenia compared to both "high" and "low inflammation" controls while ICAM1 mRNA was unchanged in leukocytes. LFA1 mRNA was decreased and CR3 mRNA was increased in leukocytes from people with schizophrenia compared to controls. LFA1 mRNA levels were positively correlated with working memory and elevated soluble ICAM1 was negatively correlated with verbal memory in schizophrenia. Altogether, some of the cognitive deficits in schizophrenia may be associated with altered expression of molecules that regulate immune cell trafficking.

Non-adherence to antipsychotic medication is common among people with schizophrenia, and is associated with an increased risk of relapse. It is important to develop strategies to enhance medication adherence. Few qualitative studies have been undertaken to understand the consumer's perspective. The voice of people who are prescribed these medications is therefore missing from the research literature. Reasons for non-adherence were investigated by directly engaging with consumers and exploring their attitudes, beliefs and experiences concerning antipsychotic medications. Qualitative, semi- structured, one-to-one interviews were conducted with 25 community-dwelling people with schizophrenia from metropolitan Adelaide, Australia. Interviews were audio-recorded, transcribed and analysed, guided by a grounded theory approach. Codes identified in open coding were grouped into categories, reflective of the different aspects of consumers' attitudes and experiences with medication. Interviews continued until there was saturation of themes. Consumer-related factors, medication-related factors and service-related factors were reported to influence adherence behavior. These included poor insight, unpleasant medication side effects, inadequate efficacy and poor therapeutic alliance. Lessons gained during periods of non-adherence were the motivator for future adherence; such as worsening of symptoms if medication was not taken. Potential implications of future adherence described by Interviewees include greater involvement of peer workers, as they were considered to work more effectively with consumers to encourage adherence. Peer workers had more credibility than other service providers due to their lived experience. Multiple factors were identified that impact on antipsychotic medication adherence, providing opportunities for interventions and improvements in services that would enhance adherence.

Objectives:We aimed to assess the incidence of obstructive sleep apnoea (OSA) in people with schizophrenia, to explore clinical associates with OSA and how well OSA screening tools perform in this population.Methods:All patients registered in a community outpatient Clozapine clinic, between January 2014 and March 2016, were consecutively approached to participate. Participants were screened for OSA using at home multichannel polysomnography (PSG) and were diagnosed with OSA if the apnoea-hypopnoea index (AHI) was >10 events/hr. Univariate comparison of participants to determine whether AHI > 10 events/hr was associated with demographic factors, anthropometric measures and psychiatric symptoms and cognition was performed. The sensitivity, specificity, positive predictive value and negative predictive value of the commonly used sleep symptoms scales and OSA screening tools were also determined.Results:Thirty participants were recruited, 24 men and 6 women. Mean age was 38.8 (range: 25–60), and mean body mass index (BMI) was 35.7 (range 19.9–62.1). The proportion of participants with OSA (AHI > 10 events/hr) was 40%, 18 (60%) had no OSA, 4 (13%) had mild OSA (AHI 10.1–20), zero participants had moderate OSA (AHI 20.1–30) and 8 (27%) had severe OSA (AHI > 30). Diagnosis of OSA was significantly associated with increased weight, BMI, neck circumference and systolic blood pressure. Diagnosis of OSA was not significantly associated with Positive and Negative Symptoms Scale, Montgomery Asperger’s Depression Rating Scale, Personal and Social Performance scale or Brief Assessment of Cognition for Schizophrenia scores. All OSA screening tools demonstrated poor sensitivity and specificity for a diagnosis of OSA.Conclusion:OSA was highly prevalent in this cohort of people with schizophrenia and was associated with traditional anthropometric OSA risk factors.

Transcranial magnetic stimulation (TMS) is a non-invasive treatment for adolescent major depressive disorder (MDD). Existing evidence on the efficacy of TMS in adolescent MDD awaits quantitative synthesis. A systematic literature search was conducted, and data from eligible studies were synthesized using random-effects models. Treatment-covariate interactions were examined in exploratory analyses of individual-patient data (IPD). Systematic search of the literature yielded 1264 hits, of which 10 individual studies (2 randomized trials) were included for quantitative synthesis of mainly uncontrolled studies. Individual patient data (IPD) were available from five trials (all uncontrolled studies). Quantitative synthesis of aggregated data revealed a statistically significant negative overall standardized mean change (pooled SMCC = 2.04, 95% CI [1.46; 2.61], SE = 0.29, p p

Following on from the publication of the Royal Australian and New Zealand Journal of Psychiatry Mood Disorder Clinical Practice Guidelines (2020) and criticisms of how these aberrantly addressed repetitive transcranial magnetic stimulation treatment of depression, questions have continued to be raised in the journal about this treatment by a small group of authors, whose views we contend do not reflect the broad acceptance of this treatment nationally and internationally. In fact, the evidence supporting the use of repetitive transcranial magnetic stimulation treatment in depression is unambiguous and substantial, consisting of an extensive series of clinical trials supported by multiple meta-analyses, network meta-analysis and umbrella reviews. Importantly, the use of repetitive transcranial magnetic stimulation treatment in depression has also been subject to a series of health economic analyses. These indicate that repetitive transcranial magnetic stimulation is a cost-effective therapy and have been used in some jurisdictions, including Australia, in support of public funding. An argument has been made that offering repetitive transcranial magnetic stimulation treatment may delay potentially effective pharmacotherapy. In fact, there is considerably greater danger of the opposite happening. Repetitive transcranial magnetic stimulation is as, if not more effective, than antidepressant medication after two unsuccessful medication trials and should be a consideration for all patients under these circumstances where available. There is no meaningful ongoing debate about the use of repetitive transcranial magnetic stimulation treatment in depression – it is a safe, effective and cost-effective treatment.

Background Health literacy (HL) has been defined as the ability of individuals to access, understand, and utilise basic health information. HL is crucial to patient engagement in treatment through supporting patient autonomy, informed consent and collaborative care. In people with physical disorders, poor HL is associated with poor health outcomes, but less is known about HL in people with severe mental illness. This study aimed to assess HL and investigate the associations between education, cognitive function, general literacy, and HL in participants with schizophrenia attending community mental health clinics. Method Fifty-two outpatients with schizophrenia attending a public community mental health clinic in Adelaide, Australia completed the Test of Functional Health Literacy in Adults—Short Form (S-TOFHLA) along with tests of cognition, aural and reading literacy and numeracy including Digit Symbol Coding (DSC), verbal fluency, the Wechsler Adult Intelligence Scale (WAIS-IV), Woodcock-Johnson III (Part 4 and 9) and the Lipkus numeracy scale. Sixty-one percent of participants were male. Participants had a mean age of 41.2 (SD 9.9) years and a mean of 11.02 (SD 1.5) years of education. Results The majority of participants had very poor aural and verbal literacy and poorer literacy correlated with fewer years of education. On the S-TOFHLA, 81% of participants had adequate HL; 6% were marginal and 13% were inadequate. There was a positive correlation between education and HL, with those with more years of education scoring higher for HL. There was also a significant association between better HL and better working memory and attention. Conclusions Consistent with previous research in schizophrenia, our participants had reduced educational attainment, aural and reading literacy and cognitive function compared to population norms. However, HL was better than expected given that previous research has found that people with psychiatric disorders tend to have lower HL, compared to the general population. This may reflect effective case management of our participants whilst attending the community clinics and supports ongoing research and intervention regarding HL in people living with mental illness.

We included all 74,960 olanzapine LAI dispensings listed in the Pharmaceutical Benefits Schedule (PBS) database from the introduction of olanzapine LAI in January 2010 until the end of January 2020. Adverse event reports for all olanzapine formulations (and the subset of olanzapine LAI) were drawn from Australian Therapeutic Goods Association Database of Adverse Event Notifications (DAEN).

Altered levels of stress-signalling transcripts have been identified in post-mortem brains of people with schizophrenia, and since stress effects may be expressed throughout the body, there should be similar changes in peripheral cells. However, the extent to which these markers are altered in peripheral white blood cells of people with schizophrenia is not known. Furthermore, how peripheral cortisol and stress-related mRNA are associated with negative symptom severity and emotional states in people with schizophrenia versus schizoaffective disorder has not been determined. Whole blood samples were collected from 86 patients with either schizophrenia or schizoaffective disorder (56 people with schizophrenia and 30 people with schizoaffective disorder), and 77 healthy controls. Total RNA was isolated, cDNA was synthesized, and stress-signalling mRNA levels (for NR3C1, FKBP5, FKBP4, PTGES3 and BAG1) were determined. Stress and symptom severity scores were measured by the Depression, Anxiety and Stress Scale, and the Positive and Negative Syndrome Scale, respectively. We found increased FKBP5 mRNA, Z(156) = 2.5, p = 0.01, decreased FKBP4 mRNA, t(155) = 3.5, p ≤ 0.001, and decreased PTGES3 mRNA, t(153) = 3.0, p ≤ 0.01, in schizophrenia and schizoaffective disorder cohorts combined compared to healthy controls. Stress-related peripheral mRNA levels were differentially correlated with negative emotional states and symptom severity in schizoaffective disorder (β's = –0.45–0.56, p's = 0.05–0.001) and schizophrenia (β's = −0.34–0.38, p's = 0.04–0.03), respectively. Therefore, molecules of the stress-signalling pathway appear to differentially contribute to clinical features of schizophrenia versus schizoaffective disorder.

The kynurenine pathway (KP) of tryptophan (TRP) catabolism links immune system activation with neurotransmitter signaling. The KP metabolite kynurenic acid (KYNA) is increased in the brains of people with schizophrenia. We tested the extent to which: (1) brain KP enzyme mRNAs, (2) brain KP metabolites, and (3) plasma KP metabolites differed on the basis of elevated cytokines in schizophrenia vs. control groups and the extent to which plasma KP metabolites were associated with cognition and brain volume in patients displaying elevated peripheral cytokines. KP enzyme mRNAs and metabolites were assayed in two independent postmortem brain samples from a total of 71 patients with schizophrenia and 72 controls. Plasma KP metabolites, cognition, and brain volumes were measured in an independent cohort of 96 patients with schizophrenia and 81 healthy controls. Groups were stratified based on elevated vs. normal proinflammatory cytokine mRNA levels. In the prefrontal cortex (PFC), kynurenine (KYN)/TRP ratio, KYNA levels, and mRNA for enzymes, tryptophan dioxygenase (TDO) and kynurenine aminotransferases (KATI/II), were significantly increased in the high cytokine schizophrenia subgroup. KAT mRNAs significantly correlated with mRNA for glial fibrillary acidic protein in patients. In plasma, the high cytokine schizophrenia subgroup displayed an elevated KYN/TRP ratio, which correlated inversely with attention and dorsolateral prefrontal cortex (DLPFC) volume. This study provides further evidence for the role of inflammation in a subgroup of patients with schizophrenia and suggests a molecular mechanism through which inflammation could lead to schizophrenia. Proinflammatory cytokines may elicit conversion of TRP to KYN in the periphery and increase the N-methyl-d-aspartate receptor antagonist KYNA via increased KAT mRNA and possibly more enzyme synthesis activity in brain astrocytes, leading to DLPFC volume loss, and attention impairment in schizophrenia.

Background: In most countries, clozapine can only be prescribed with regular monitoring of white blood cell counts because of concerns that clozapine has a stronger association with neutropenia than other antipsychotics. However, this has not been previously demonstrated conclusively with meta-analysis of controlled studies. Methods: The aim of this study was to assess the strength of the association between clozapine and neutropenia when compared to other antipsychotic medications by a meta-analysis of controlled studies. An electronic search of Medline (1948–2018), PsycINFO (1967–2018) and Embase (1947–2018) using search terms (clozapine OR clopine OR clozaril OR zaponex) AND (neutropenia OR agranulocytosis) was undertaken. Random-effects meta-analysis using Mantel–Haenszel risk ratio was used to assess the strength of the effect size. Results: We located 20 studies that reported rates of neutropenia associated with clozapine and other antipsychotic medications. The risk ratio was not significantly increased in clozapine-exposed groups compared to exposure to other antipsychotic medications (Mantel–Haenszel risk ratio = 1.45, 95% confidence interval = [0.87, 2.42]). This also applied to severe neutropenia (absolute neutrophil count Conclusion: Data from controlled trials do not support the belief that clozapine has a stronger association with neutropenia than other antipsychotic medications. This implies that either all antipsychotic drugs should be subjected to haematological monitoring or monitoring isolated to clozapine is not justified.

IntroductionThere are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD.Methods and analysisThis study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14–40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024.Ethics and disseminationThe study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia’s National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12620000890932).

Objective: While there is considerable current emphasis on youth and early psychosis, relatively little is known about the lives of people who live with psychotic disorders into middle age and beyond. We investigated social functioning, physical health status, substance use and psychiatric symptom profile in people with psychotic disorders aged between 50 and 65 years. Methods: Data were collected as part of the Survey of High Impact Psychosis, a population-based survey of Australians aged 18–65 years with a psychotic disorder. We compared those aged 50–65 years ( N = 347) with those aged 18–49 years ( N = 1478) across a range of measures. Results: The older group contained more women and more people with affective psychoses compared to the younger group. They were also more likely to have had a later onset and a chronic course of illness. The older group were more likely to have negative symptoms but less likely to exhibit positive symptoms; they also had lower current cognition, compared to the younger group. Compared to the younger group, the older group were more likely to be divorced/separated, to be living alone and to be unemployed. They had substantially lower lifetime use of alcohol and illicit substances, but rates of obesity, metabolic syndrome and diabetes mellitus were higher. Conclusion: Our findings suggest that the characteristics of people with psychosis change significantly as they progress into the middle age and beyond. A better understanding of these differences is important in informing targeted treatment strategies for older people living with psychosis.

While high levels of glucocorticoids are generally neuro-damaging, a related adrenal steroid, dehydroepiandrosterone (DHEA), has anti-glucocorticoid and neuroprotective properties. Previous work has shown increased circulating levels of DHEA and abnormal cortisol/DHEA ratios in people with schizophrenia, however reports are limited and their relationship to neuropathology is unclear. We performed the largest study to date to compare levels of serum DHEA and cortisol/DHEA ratios in people with schizophrenia and healthy controls, and investigated the extent to which cortisol/DHEA ratios predict brain volume. Serum cortisol and DHEA were assayed in 94 people with schizophrenia and 81 healthy controls. T1-weighted high-resolution anatomical scans were obtained using a 3 T Achieva scanner on a subset of 59 people with schizophrenia and 60 healthy controls. Imaging data were preprocessed and analyzed using SPM12. People with schizophrenia had significantly increased serum DHEA levels (p = 0.002), decreased cortisol/DHEA ratios (p = 0.02) and no difference in cortisol levels compared to healthy controls. Cortisol/DHEA ratios were inversely correlated with hippocampal (r = -0.33 p = 0.01) and dorsolateral prefrontal cortex (r = -0.30, p = 0.02) volumes in patients. Our findings suggest that the cortisol/DHEA ratio may be a molecular blood signature of hippocampal and cortical damage. These results further implicate the role of DHEA and hypothalamic-pituitary-adrenal axis dysfunction in the pathophysiology of schizophrenia.

Background: This paper discusses the process of co-design of a de-colonising participatory methodology that enabled an international PhD student to work respectfully with Aboriginal community members and Elders, health professionals and consumers, and non-Indigenous service providers in a drug and alcohol and mental health comorbidity project in Adelaide, South Australia. The Comorbidity Action in the North project sought to redesign services to better meet the needs of local people affected by drug, alcohol, and mental health comorbidity. This arm of the study focused on the needs of Indigenous peoples. Methods: The PhD student, Aboriginal Elder mentor, Aboriginal Working Party and supervisors (the research team) sought to co-design a methodology that could address the following challenges: many Aboriginal people deeply distrust Western research due to past poor practices and a lack of implementation of findings into practice; Aboriginal people often remain unheard, unacknowledged and unrecognised in research projects; drug and alcohol and mental health comorbidity experiences are often distressing for Aboriginal community members and their families; attempts to access comorbidity care often result in limited or no access; Aboriginal community members experience acts of racism and discrimination as health professionals and consumers of health and support services; and, the PhD student was an international student with no existing relationship with local Aboriginal community members. The research team considered deeply how knowledge is shared, interpreted, owned and controlled, by whom and how, within research, co-morbidity care and community settings. The PhD student was supported to co-design a methodology that was equitable, democratic, liberating and life-enhancing, with real potential to develop feasible solutions. Results: The resulting combined Participatory Action Research (PAR)-Dadirri-Ganma methodology sought to create a bridge across Western and Aboriginal knowledges, understanding and experiences. Combined mentoring by senior Elders, Indigenous methodologies Dadirri (deep listening) and Ganma (two-way knowledge sharing), and Western PAR.Conclusions: Concepts within this paper are shared from the perspective of the PhD student with the permission and support of local Elders and Working Group members. The intention is to share what was learned for the benefit other students, research projects and community members who are beginning a similar journey.

Background Repetitive Transcranial Magnetic Stimulation (rTMS) is a safe and effective treatment for treatment resistant depression (TRD). The number of patients able to be treated with rTMS is determined by the availability of the machine and staff. If treatment delivered in a shorter time were just as effective as longer treatments, then more patients could be treated with the same resources. Method This naturalistic study investigated 145 first-time patients treated with 15 minute (900 pulses) or 30 minute (1800 pulses) RLF rTMS for TRD 3 days/week for 6 weeks. Response and remission rates for the two groups were compared. We investigated whether longer right unilateral low (1Hz) frequency (RLF) repetitive transcranial magnetic stimulation (rTMS) treatment sessions are more effective than shorter sessions in achieving response and remission for treatment resistant depression (TRD). Results The duration of rTMS treatment sessions had no effect on treatment outcomes over the course of 6 weeks. The group treated with 15 minute rTMS sessions showed a partial response rate of 28.2%, a response rate of 11.5% and remission rate of 21.8%, which did not differ significantly from patients receiving 30 minute sessions who had a partial response rate of 25.4%, response rate of 17.9% and remission rate of 22.4%. Limitations Participants were not randomized and the inclusion criteria were broad and reflected the nature of patients seen in routine practice. Conclusions Fifteen minute rTMS sessions 3 days/week for 6 weeks were as effective as 30 minute sessions, providing a pragmatic advantage for shorter treatments.

Objective: A narrative review to describe the utility of the neutrophil-lymphocyte ratio (NLR) as an inflammatory marker in psychiatric and non-psychiatric disorders and to discuss the potential role of NLR in psychiatric research. Conclusions: NLR is inexpensive and readily available using division of two measures obtained on routine blood testing. NLR is elevated in a number of psychiatric disorders. It can predict morbidity and mortality in a wide range of non-psychiatric conditions, but this has not been confirmed in psychiatric conditions. It can be calculated in large, pre-existing datasets to investigate clinical correlates of inflammatory processes. NLR may have a future role in identifying patients with an inflammatory phenotype who could benefit from adjunctive anti-inflammatory medications.

Individualized metacognitive training (MCT+) is a novel psychotherapy that has been designed to specifically target delusional beliefs in people with psychosis. It works by developing an awareness of the implausible content of delusional beliefs, while also targeting the cognitive biases that contribute to their formation and maintenance. It was expected that MCT+ would lead to significantly greater reductions in delusional severity compared to a cognitive remediation (CR) active control condition. A total of 54 patients with a schizophrenia spectrum disorder and active delusions were randomized into four 2-hourly sessions of MCT+ (n = 27) or CR (n = 27). All participants completed posttreatment assessment, and only 2 participants did not complete 6-month follow-up assessment, resulting in MCT+ (n = 26) and CR (n = 26) for final analysis. The primary outcome measures of delusional and positive symptom severity were assessed rater-blind; secondary outcome assessment was non-blinded and included clinical and cognitive insight, the jumping to conclusions (JTC) bias, and cognitive functioning. Participants in the MCT+ condition showed significant reductions in delusional and overall positive symptom severity (large effect) and improved clinical insight (moderate effect) relative to CR controls. In contrast, CR controls showed moderate improvement in problem-solving ability relative to MCT+, but no other cognitive domain. Importantly, these findings were maintained at 6-month follow-up. The study adds further efficacy to the MCT program, and suggests that even brief psychotherapy can help to ameliorate the symptoms of psychosis.

Aim: Depression is common in young people, and there is a need for safe, effective treatments. This study examined the efficacy of repetitive transcranial magnetic stimulation in a sample of young people aged 17 to 25 years. Methods: This retrospective study included 15 people aged 17 to 25 years referred by their private psychiatrists affiliated with Ramsay Health Care, South Australia Mental Health Services. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for treatment-resistant Major Depressive Disorder. Eleven patients received right unilateral treatment and four patients received bilateral treatment. Patients were assessed at baseline and after treatment. Results: There was a significant improvement on the Hamilton Rating Scale for Depression (t(14) = 4.71, P < 0.0001); Montgomery-Åsperg Depression Rating Scale (t(14) = 3.96, P < 0.01) and the Zung Self-Rating Depression Scale (t(14) = 4.13, P < 0.01). There was no difference in response by gender or age. The response rates in these young people did not differ significantly from those of adults aged 25 to 82 years. Conclusion: This open label, naturalistic study suggests that repetitive transcranial magnetic stimulation is an effective treatment in young adults who have treatment-resistant depression. Randomized sham-controlled studies are needed to further investigate the efficacy of this treatment in this age group Refereed/Peer-reviewed

Elevated pro-inflammatory cytokines exist in both blood and brain of people with schizophrenia but how this affects molecular indices of the blood–brain barrier (BBB) is unclear. Eight mRNAs relating to BBB function, a microglia and three immune cell markers were measured by qPCR in the prefrontal cortex from 37 people with schizophrenia/schizoaffective disorder and 37 matched controls. This cohort was previously grouped into “high inflammation” and “low inflammation” subgroups based on cortical inflammatory-related transcripts. Soluble intercellular adhesion molecule-1 (sICAM1) was measured in the plasma of 78 patients with schizophrenia/schizoaffective disorder and 73 healthy controls. We found that sICAM1 was significantly elevated in schizophrenia. An efflux transporter, ABCG2, was lower, while mRNAs encoding VE-cadherin and ICAM1 were higher in schizophrenia brain. The “high inflammation” schizophrenia subgroup had lower ABCG2 and higher ICAM1, VE-cadherin, occludin and interferon-induced transmembrane protein mRNAs compared to both “low inflammation” schizophrenia and “low inflammation” control subgroups. ICAM1 immunohistochemistry showed enrichment in brain endothelium regardless of diagnosis and was localised to astrocytes in some brains. Microglia mRNA was not altered in schizophrenia nor did it correlate with ICAM1 expression. Immune cell mRNAs were elevated in “high inflammation” schizophrenia compared to both “low inflammation” schizophrenia and controls. CD163+ perivascular macrophages were identified by immunohistochemistry in brain parenchyma in over 40% of “high inflammation” schizophrenia brains. People with high levels of cytokine expression and schizophrenia display changes consistent with greater immune cell transmigration into brain via increased ICAM1, which could contribute to other neuropathological changes found in this subgroup of people.

Objectives: Schizophrenia is a debilitating psychiatric illness associated with positive and negative symptoms as well as significant impairments in cognition. Current antipsychotic medications do not alleviate these cognitive deficits, and more effective therapeutic options are required. Increased oxidative stress and altered antioxidant levels, including glutathione (GSH) have been observed both in individuals with cognitive impairment and in people with schizophrenia. A GSH precursor, the antioxidant N-acetylcysteine (NAC) has been investigated as a novel treatment for the cognitive symptoms of schizophrenia, and recent research suggests that NAC may be a promising adjunctive treatment option. However, the current literature lacks integration as to why NAC may effectively improve cognition in schizophrenia. The present theoretical synthesis aimed to address this gap by examining the processes by which NAC may improve cognitive function in schizophrenia. Methods: The schizophrenia literature was reviewed in three key domains: cognitive impairment, the relationship between oxidative stress and cognition, and the efficacy of NAC as a novel treatment. This led to a theoretical analysis of the neurobiological processes by which NAC may improve cognition in schizophrenia. Results: This theoretical review concluded that improved cognition may result from a combination of factors, including decreased oxidative stress, neuroprotection of cognitive networks and an increase in glutamatergic modulation of the N-methyl-d-aspartate receptor system. Whilst a number of mechanisms by which NAC may improve cognition and symptoms in schizophrenia have been proposed, there is still limited understanding of the specific metabolic pathways involved and how they interrelate and modify specific symptomology. Discussion: Exploration of how NAC treatment may act to improve cognitive function could guide clinical trials by investigation of the specific neurotransmitter systems and processes involved, allowing for targeted neurological outcome measures. Future research would benefit from the investigation of both in vivo cortical GSH concentration and peripheral plasma GSH in a population of individuals with chronic schizophrenia.

BACKGROUND: Clozapine is associated with life-threatening neutropenia. There are no previous meta-analyses of the epidemiology of clozapine-associated neutropenia. OBJECTIVES: To determine the cumulative incidence of mild, moderate and severe neutropenia, incidence of death related to severe neutropenia, case fatality rate of neutropenia and the longitudinal incidence of neutropenia following exposure to clozapine. DATA SOURCES: A systematic search of Medline, EMBASE and PsycINFO using search terms [clozapine OR clopine OR zaponex OR clozaril] AND [neutropenia OR agranulocytosis]. METHODS: Random effects meta-analysis to determine event rates and longitudinal incidence of events per 100 person-years of exposure. RESULTS: A total of 108 studies were included. The incidence of clozapine-associated neutropenia was 3.8% (95% CI: 2.7-5.2%) and severe neutropenia 0.9% (95% CI: 0.7-1.1%). The incidence of death related to neutropenia following prescription of clozapine was 0.013% (95% CI: 0.01-0.017%). The case fatality rate of severe neutropenia was 2.1% (95% CI: 1.6-2.8%). The peak incidence of severe neutropenia occurred at one month of exposure and declined to negligible levels after one year of treatment. CONCLUSION: Severe neutropenia associated with clozapine is a rare event and occurs early with a substantial decline in risk after one year of exposure. Death from clozapine-associated neutropenia is extremely rare. Implications for haematological monitoring are discussed.

Objectives:Obstructive sleep apnoea (OSA) may be more common in people with schizophrenia compared to the general population, but the relative prevalence is unknown. Here, we determine the relative prevalence of severe OSA in a cohort of men with schizophrenia compared to representative general population controls, and investigate the contribution of age and body mass index (BMI) to differences in prevalence.Methods:Rates of severe OSA (apnoea–hypopnoea index > 30) were compared between male patients with schizophrenia and controls from a representative general population study of OSA.Results:The prevalence of severe OSA was 25% in the schizophrenia group and 12.3% in the general population group. In subgroups matched by age, the relative risk of severe OSA was 2.9 ( p = 0.05) in the schizophrenia subjects, but when adjusted for age and BMI, the relative risk dropped to 1.7 and became non-significant ( p = 0.17).Conclusions:OSA is prevalent in men with schizophrenia. Obesity may be an important contributing factor to the increased rate of OSA.

Objective: Parenthood is central to the personal and social identity of many people. For individuals with psychotic disorders, parenthood is often associated with formidable challenges. We aimed to identify predictors of adequate parenting among parents with psychotic disorders. Methods: Data pertaining to 234 parents with psychotic disorders living with dependent children were extracted from a population-based prevalence study, the 2010 second Australian national survey of psychosis, and analysed using confirmatory factor analysis. Parenting outcome was defined as quality of care of children, based on participant report and interviewer enquiry/exploration, and included level of participation, interest and competence in childcare during the last 12 months. Results: Five hypothesis-driven latent variables were constructed and labelled psychosocial support, illness severity, substance abuse/dependence, adaptive functioning and parenting role. Importantly, 75% of participants were not identified to have any dysfunction in the quality of care provided to their child(ren). Severity of illness and adaptive functioning were reliably associated with quality of childcare. Psychosocial support, substance abuse/dependence and parenting role had an indirect relationship to the outcome variable via their association with either severity of illness and/or adaptive functioning. Conclusion: The majority of parents in the current sample provided adequate parenting. However, greater symptom severity and poorer adaptive functioning ultimately leave parents with significant difficulties and in need of assistance to manage their parenting obligations. As symptoms and functioning can change episodically for people with psychotic illness, provision of targeted and flexible support that can deliver temporary assistance during times of need is necessary. This would maximise the quality of care provided to vulnerable children, with potential long-term benefits.