Adjunctive canakinumab reduces peripheral inflammation markers and improves positive symptoms in people with schizophrenia and inflammation: A randomized control trial.

BACKGROUND: Clinical trials of anti-inflammatories in schizophrenia do not show clear and replicable benefits, possibly because patients were not recruited based on elevated inflammation status. Interleukin 1-beta (IL-1ß) mRNA and protein levels are increased in serum, plasma, cerebrospinal fluid, and brain of some chronically ill patients with schizophrenia, first episode psychosis, and clinical high-risk individuals. Canakinumab, an approved anti-IL-1ß monoclonal antibody, interferes with the bioactivity of IL-1ß and interrupts downstream signaling. However, the extent to which canakinumab reduces peripheral inflammation markers, such as, high sensitivity C-reactive protein (hsCRP) and symptom severity in schizophrenia patients with inflammation is unknown. TRIAL DESIGN: We conducted a randomized, placebo-controlled, double-blind, parallel groups, 8-week trial of canakinumab in chronically ill patients with schizophrenia who had elevated peripheral inflammation. METHODS: Twenty-seven patients with schizophrenia or schizoaffective disorder and elevated peripheral inflammation markers (IL-1ß, IL-6, hsCRP and/or neutrophil to lymphocyte ratio: NLR) were randomized to a one-time, subcutaneous injection of canakinumab (150 mg) or placebo (normal saline) as an adjunctive antipsychotic treatment. Peripheral blood hsCRP, NLR, IL-1ß, IL-6, IL-8 levels were measured at baseline (pre injection) and at 1-, 4- and 8-weeks post injection. Symptom severity was assessed at baseline and 4- and 8-weeks post injection. RESULTS: Canakinumab significantly reduced peripheral hsCRP over time, F(3, 75) = 5.16, p = 0.003. Significant hsCRP reductions relative to baseline were detected only in the canakinumab group at weeks 1, 4 and 8 (p's = 0.0003, 0.000002, and 0.004, respectively). There were no significant hsCRP changes in the placebo group. Positive symptom severity scores were significantly reduced at week 8 (p = 0.02) in the canakinumab group and week 4 (p = 0.02) in the placebo group. The change in CRP between week 8 and baseline (b = 1.9, p = 0.0002) and between week 4 and baseline (b = 6.0, p = 0.001) were highly significant predictors of week 8 change in PANSS Positive Symptom severity scores. There were no significant changes in negative symptoms, general psychopathology or cognition in either group. Canakinumab was well tolerated and only 7 % discontinued. CONCLUSIONS: Canakinumab quickly reduces peripheral hsCRP serum levels in patients with schizophrenia and inflammation; after 8 weeks of canakinumab treatment, the reductions in hsCRP are related to reduced positive symptom severity. Future studies should consider increased doses or longer-term treatment to confirm the potential benefits of adjunctive canakinumab in schizophrenia. Australian and New Zealand Clinical Trials Registry number: ACTRN12615000635561.

Do benzodiazepines reduce the efficacy of transcranial magnetic stimulation?

OBJECTIVE: To investigate the effect of concomitant use of benzodiazepines on the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with treatment-resistant major depressive disorder (TR-MDD). METHODS: This is a retrospective study comparing rTMS treatment outcomes between patients taking benzodiazepines (n = 59) and those who were not (n = 136). Participants completed the HAM-A, HAM-D17, MADRS and ZUNG at baseline and at the end of treatment. RESULTS: Patients taking benzodiazepines during rTMS treatment did not show any difference in partial response, response or remission rates compared to patients not treated with benzodiazepines. There was a significant decrease (p < .0001) in depression and anxiety scores from baseline to post-treatment among both groups. CONCLUSIONS: Concomitant benzodiazepine treatment had no effect on the efficacy of rTMS treatment of TRD, contrary to previous research.

Peripheral complement is increased in schizophrenia and inversely related to cortical thickness.

BACKGROUND: There is growing evidence for complement system involvement in the pathophysiology of schizophrenia, although the extent and magnitude of complement factor disturbances has not been fully reported. It also remains unclear whether complement abnormalities are characteristic of all patients with schizophrenia or whether they are representative of a subgroup of patients who show signs of heightened inflammation. The aim of the present study was to quantify and compare the levels of a range of complement factors, receptors and regulators in healthy controls and people with schizophrenia and to determine the extent to which the levels of these peripheral molecules relate to measures of brain structure, particularly cortical thickness. METHOD: Seventy-five healthy controls and 90 patients with schizophrenia or schizoaffective disorder were included in the study. Peripheral blood samples were collected from all participants and mRNA expression was quantified in 20 complement related genes, four complement proteins, as well as for four cytokines. T1-weighted structural MRI scans were acquired and analysed to determine cortical thickness measures. RESULTS: There were significant increases in peripheral mRNA encoding receptors (C5ar1, CR1, CR3a), regulators (CD55, C59) and protein concentrations (C3, C3b, C4) in people with schizophrenia relative to healthy controls. C4a expression was significantly increased in a subgroup of patients displaying elevated peripheral cytokine levels. A higher inflammation index score derived from mRNA expression patterns predicted reductions in cortical thickness in the temporal lobe (superior temporal gyrus, transverse temporal gyrus, fusiform gyrus, insula) in patients with schizophrenia and healthy controls. CONCLUSIONS: Analysis of all three major complement pathways supports increased complement activity in schizophrenia and also shows that peripheral C4a up-regulation is related to increased peripheral pro-inflammatory cytokines in healthy controls. Our region-specific, neuroimaging findings linked to an increased peripheral complement mRNA expression pattern suggests a role for complement in cortical thinning. Further studies are required to further clarify clinical and neurobiological consequences of aberrant complement levels in schizophrenia and related psychoses.

Associations between health literacy, cognitive function and general literacy in people with schizophrenia attending community mental health clinics in Australia.

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.

Ageing with psychosis - Fifty and beyond.

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.

Revisiting the effectiveness of repetitive transcranial magnetic stimulation treatment in depression, again.

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.

Transcranial magnetic stimulation in the treatment of adolescent depression: a systematic review and meta-analysis of aggregated and individual-patient data from uncontrolled studies.

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 < .001), as well as a significant overall treatment response rate (Transformed Proportion = 41.30%, 95% CI [31.03; 51.57], SE = 0.05; p < 0.001), considering data from baseline to post-treatment. Exploratory IPD analyses suggests TMS might be more effective in younger individuals and individuals with more severe depression, and efficacy might be enhanced with certain treatment modality settings, including higher number of TMS sessions, longer treatment durations, and unilateral and not bilateral stimulation. Existing studies exhibit methodological shortcomings, including small-study effects and lack of control group, blinding, and randomization-compromising the credibility of the present results. To date, two randomized controlled trials on TMS in adolescent depression have been published, and the only large-scale randomized trial suggests TMS is not more effective than sham stimulation. Future large-scale, randomized, and sham-controlled trials are warranted. Future trials should ensure appropriate selection of patients for TMS treatment and guide precision medicine approaches for stimulation protocols.

Improving services for those who serve: A private practice initiative to improve psychiatric care for first responder and military patients.

OBJECTIVES: Professional isolation and limited opportunities for multidisciplinary collaborations are well-recognised challenges for psychiatrists in private practice. This narrative paper describes the development of a private practice group to assist first responders (FRs) and military patients located in Adelaide, South Australia. The aims included both peer review, and interdisciplinary communication and collaboration. Relevant personnel in the ambulance, police and fire services, military and veterans' groups, and the compensation system, participated in monthly meetings. Lack of timely access to psychiatric care for FR and military patients was identified as a problem and an expedited referral service was established. CONCLUSIONS: The Closing the Gap Group was established in 2017. The terminology refers to the gap between treating psychiatrists and the complex organisations that manage the workplace context for FR/military patients. This initiative provides a template for private practice innovations to improve psychiatrists' skills and knowledge, along with better engagement and understanding between private psychiatrists and relevant community organisations.

Is PTSD a Bodily Injury?

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.

The characteristics of older homicide offenders: a systematic review.

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.

Increased macrophages and changed brain endothelial cell gene expression in the frontal cortex of people with schizophrenia displaying inflammation.

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.

Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia.

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.

Participatory Action Research-Dadirri-Ganma, using Yarning: methodology co-design with Aboriginal community members.

BACKGROUND: Appropriate choice of research design is essential to rightly understand the research problem and derive optimal solutions. The Comorbidity Action in the North project sought to better meet the needs of local people affected by drug, alcohol and mental health comorbidity. The aim of the study focused on the needs of Aboriginal peoples and on developing a truly representative research process. A methodology evolved that best suited working with members of a marginalised Aboriginal community. This paper discusses the process of co-design of a Western methodology (participatory action research) in conjunction with the Indigenous methodologies Dadirri and Ganma. This co-design 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. METHODS: The PhD student, Aboriginal Elder mentor, Aboriginal Working Party, and supervisors (the research team) sought to co-design a methodology and applied it to address the following challenges: the PhD student was an international student with no existing relationship with local Aboriginal community members; 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; and Aboriginal community members experience acts of racism and discrimination as health professionals and consumers of health and support services. 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. Foundation pillars of this bridge were mentoring of the PhD student by senior Elders, who explained and demonstrated the critical importance of Yarning (consulting) and Indigenous methodologies of Dadirri (deep listening) and Ganma (two-way knowledge sharing), and discussions among all involved about the principles of 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 of other students, research projects and community members who are beginning a similar journey.

Altered levels of immune cell adhesion molecules are associated with memory impairment in schizophrenia and healthy controls.

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.

Improvement of cognitive function in schizophrenia with N-acetylcysteine: A theoretical review.

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.

The neuropsychiatric effects of vitamin C deficiency: a systematic review.

BACKGROUND: Vitamin C deficiency may be more common than is generally assumed, and the association between vitamin C deficiency and adverse psychiatric effects has been known for centuries. This paper aims to systematically review the evidence base for the neuropsychiatric effects of vitamin C deficiency. METHODS: Relevant studies were identified via systematic literature review. RESULTS: Nine studies of vitamin C deficiency, including subjects both with and without the associated physical manifestations of scurvy, were included in this review. Vitamin C deficiency, including scurvy, has been linked to depression and cognitive impairment. No effect on affective or non-affective psychosis was identified. CONCLUSIONS: Disparate measurement techniques for vitamin C, and differing definitions of vitamin C deficiency were apparent, complicating comparisons between studies. However, there is evidence suggesting that vitamin C deficiency is related to adverse mood and cognitive effects. The vitamin C blood levels associated with depression and cognitive impairment are higher than those implicated in clinical manifestations of scurvy. While laboratory testing for ascorbic acid can be practically difficult, these findings nonetheless suggest that mental health clinicians should be alerted to the possibility of vitamin C deficiency in patients with depression or cognitive impairment. Vitamin C replacement is inexpensive and easy to deliver, although as of yet there are no outcome studies investigating the neuropsychiatric impact of vitamin C replacement in those who are deficient.

A qualitative study of medication adherence amongst people with schizophrenia.

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.

Identifying and exploring linguistic expertise of psychiatrists in interviews with patients with thought disorder.

OBJECTIVE: To identify and understand the linguistic expertise of psychiatrists in clinical interviews with patients experiencing thought disorder (TD). METHOD: Qualitative analysis of 24 routine clinical interviews between psychiatrists and inpatients with TD. RESULTS: Psychiatrists demonstrated the expertise with which they navigated clinical interviews and accomplished shared goals with patients experiencing TD. These findings highlight the need to rethink the notion that such patients are incapable of productive communication. Capturing and describing psychiatrists' tacit expertise provides a foundation for documenting an under-recognised skill set. CONCLUSIONS: Understanding such expertise could enhance the care of patients with TD, repositioning them as active participants in the accomplishment of shared therapeutic goals. Teaching these skills to mental health clinicians during their training would improve their ability to establish effective therapeutic relationships with these patients.

Supporting the vulnerable: developing a strategic community mental health response to the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic poses significant risks to the vulnerable patient population supported by community mental health (CMH) teams in South Australia. This paper describes a plan developed to understand and mitigate these risks. METHODS: Public health and psychiatric literature was reviewed and clinicians in CMH teams and infectious disease were consulted. Key risks posed by COVID-19 to CMH patients were identified and mitigation plans were prepared. RESULTS: A public health response plan for CMH teams was developed to support vulnerable individuals and respond to the COVID-19 pandemic. This plan will be reviewed regularly to respond to changes in public health recommendations, research findings and feedback from patients and clinicians. CONCLUSIONS: The strategic response plan developed to address risks to vulnerable patients from COVID-19 can assist other CMH services in managing the COVID-19 pandemic.

Neutrophil-lymphocyte ratio - a simple, accessible measure of inflammation, morbidity and prognosis in psychiatric disorders?

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.