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Aim Deep brain stimulation (DBS) is a safe and effective treatment option for people with refractory obsessive-compulsive disorder (OCD). Yet our understanding of predictors of response and prognostic factors remains rudimentary, and long-term comprehensive follow-ups are lacking. We aim to investigate the efficacy of DBS therapy for OCD patients, and predictors of clinical response. Methods Eight OCD participants underwent DBS stimulation of the nucleus accumbens (NAc) in an open-label longitudinal trial, duration of follow-up varied between 9 months and 7 years. Post-operative care involved comprehensive fine tuning of stimulation parameters and adjunct multidisciplinary therapy. Results Six participants achieved clinical response (35% improvement in obsessions and compulsions on the Yale Brown Obsessive Compulsive Scale (YBOCS)) within 6–9 weeks, response was maintained at last follow up. On average, the YBOCS improved by 45% at last follow up. Mixed linear modeling elucidated directionality of symptom changes: insight into symptoms strongly predicted (P = 0.008) changes in symptom severity during DBS therapy, likely driven by initial changes in depression and anxiety. Precise localization of DBS leads demonstrated that responders most often had their leads (and active contacts) placed dorsal compared to non-responders, relative to the Nac. Conclusion The clinical efficacy of DBS for OCD is demonstrated, and mediators of changes in symptoms are proposed. The symptom improvements within this cohort should be seen within the context of the adjunct psychological and biopsychosocial care that implemented a shared decision-making approach, with flexible iterative DBS programming. Further research should explore the utility of insight as a clinical correlate of response. The trial was prospectively registered with the ANZCTR (ACTRN12612001142820).

BACKGROUND: Many cancer survivors experience cancer-related cognitive impairment (CRCI), often with significant negative consequences across various life domains. Emerging evidence suggests that allowing additional time to process information before acting may be a useful strategy for those with CRCI to mitigate some of its impacts. The Wisconsin Card Sorting Task (WCST), a measure of general cognition, has shown that for some cancer survivors, longer task completion time facilitates similar task performance outcomes to control populations concerning perseveration errors; a key performance metric of the WCST. However, assessing if this strategy may be useful, as well as determining for whom it may be useful, with regard to strengths and weaknesses among select cognitive domains, is challenging due to factors such as the problem of task impurity. Accordingly, this study provides an initial computational and experimental assessment of whether additional time to process information before acting is a useful strategy for those with CRCI. METHODS: We simulated individual cognitive differences observed in humans by varying contributions of executive functioning components (updating, shifting, inhibition) to yield 48 distinct computational models of the WCST. Our main manipulation was then to provide these models with more or less time (at three levels of 20, 40 and 60 cycles) before models executed an action to sort a given card. We compared the number of perseveration errors on the WCST produced by the computational models. Additionally, we determined models that simulated the performance of cancer survivors on the WCST by comparing the number of perseveration errors produced by the models to human data. RESULTS: Additional processing time resulted in the models producing significantly fewer perseveration errors, supporting our hypothesis. In addition, 8 unique models simulated the performance of cancer survivors on the WCST. Additional time appeared to have a positive i

Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy (1H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) (n = 20) or placebo (n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA (p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response.

This paper explores the lived experience of mental illness within the field of psychology across higher education and the mental health workforce. There is a high prevalence of mental health issues among psychology students and practitioners, and it is critical not only to provide support for these populations, but also to acknowledge the value of leveraging their lived experience within their education and practice. There has been increased interest in and advocacy for the involvement of those with lived experience of mental illness within mental healthcare service provision to improve patient experiences and outcomes. However, there have been limited acknowledgement and research regarding the role of psychologists with personal lived experiences of mental illness, and how to leverage this experience. Further, there are challenges faced by both psychology students and practising psychologists with lived experience that act as barriers to leveraging their unique skills and experiences. Psychology students with lived experience face stigma, inadequate support, and incongruence between the course material and their personal experiences. Similarly, practising psychologists with lived experience encounter stigma and isolation, indicating the need for a culture change that promotes transparency and understanding. The paper calls for research in five key directions to provide evidence that can be used to support and leverage lived experience in psychology.

The authors wish to correct the following error in this paper [...].

Although telomere attrition is associated with the process of normal ageing, shorter telomere length (TL) has been associated with acute and chronic stressors. A neurobiological factor hypothesised to be responsible for this accelerated attrition is the dysregulation of the cortisol stress response, which can induce DNA damage affecting DNA telomeric caps. Marked sex differences are reported in both the cortisol stress response and telomere dynamics, yet no explicit investigation of sex specificity on the relationship between cortisol and TL exists. This study used mathematical equation modelling to describe the relationship between diurnal cortisol levels and telomere length within the context of sex, in a healthy population. Cortisol awakening responses (CAR) were measured via ELISA methodology in fifty-one healthy participants (28 males, 23 females). qPCRs determined TL from genomic DNA extracted from saliva. To assess the effect of free cortisol on relative TL ratio, a semi-log regression plot of the two variables trended for sex were fitted using spline curves. Results demonstrated significant differences between males and females in the relationship defining CAR and TL association (p = 0.03). These results suggest the relationship is not linear and can be represented as a complex arcsin function, and that the patterns are opposite in males and females. Males demonstrate a positive correlation, with higher levels of CAR being associated with longer telomere sequences. Females demonstrated a negative correlation. Future studies must carefully take into consideration moderating factors such as sex, and sex hormones across the lifespan when investigating telomere length.

INTRODUCTION: For some people, COVID-19 infection leads to negative health impacts that can last into the medium or long term. The long-term sequelae of COVID-19 infection, or 'long COVID', negatively affects not only physical health, but also mental health, cognition or psychological well-being. Complex, integrated interventions are recommended for long COVID, including psychological components; however, the effectiveness of such interventions has yet to be critically evaluated. This protocol describes a systematic review to be conducted of scientific literature reporting on clinical trials of interventions to promote mental health, cognition or psychological well-being among individuals with long COVID. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A health sciences librarian will identify the relevant literature through comprehensive systematic searches of Medline, Embase, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, medRxiv, PsyArXiv, China National Knowledge Internet and WANFANG Data databases, as well as The Cochrane Central Register of Controlled Trials, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform. Studies will be selected through a title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Data extracted will include intervention descriptions and efficacy metrics. Data will be narratively synthesised; if the data allow, a meta-analysis will be conducted. Risk of bias assessment will be conducted using the Cochrane Risk of Bias 2.0 tool. ETHICS AND DISSEMINATION: Ethical approval for systematic reviews is not required. As researchers and clinicians respond to the new clinical entity that long COVID represents, this review will synthesise a rapidly emerging evidence base describing and testing interventions to promote mental health, cognition or psychological well-being. Results will th

BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from t

OBJECTIVES: Auditory verbal hallucinations (AVHs) occur as a symptom in various mental disorders, and show different phenomenological aspects, depending on their underlying psychopathology. Anxiety and depression, which are known to be involved in the development of AVHs, are suggested to amplify a vicious cycle in which negative interpretations of daily experiences feed into the formation of negative core schemas about the self and others. However, the way in which these variables interrelate is still unknown. Therefore, our aim was to determine the specific roles of anxiety and depression in the relationship between core schemas and emotional aspects of AVHs for three groups (non-clinical voice hearers, affective voice hearers and non-affective voice hearers). METHODS: Positive and negative core schemas of the self and others were tested as predictors of emotional distress due to AVHs, examining anxiety and depression separately as potential mediators. RESULTS: Results showed full mediating effects of depression in non-affective voice hearers in the relationship between negative core schemas and AVH distress, but not in affective voice hearers. Anxiety was not a mediator in any of the groups. CONCLUSIONS: These findings suggest different emotional mechanisms depending on the underlying psychopathology.

Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from t

The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the ‘Clinical Memorandum on Psychedelics’ recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymethamphetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to individuals and detrimental to the field.

Invasive and noninvasive neurostimulation therapies for obsessive-compulsive and related disorders (OCRD) were systematically reviewed with the aim of assessing clinical characteristics, methodologies, neuroanatomical substrates, and varied stimulation parameters. Previous reviews have focused on a narrow scope, statistical rather than clinical significance, grouped together heterogenous protocols, and proposed inconclusive outcomes and directions. Herein, a comprehensive and transdiagnostic evaluation of all clinically relevant determinants is presented with translational clinical recommendations and novel response rates. Electroconvulsive therapy (ECT) studies were limited in number and quality but demonstrated greater efficacy than previously identified. Targeting the pre-SMA/SMA is recommended for transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). TMS yielded superior outcomes, although polarity findings were conflicting, and refinement of frontal/cognitive control protocols may optimize outcomes. For both techniques, standardization of polarity, more treatment sessions (>20), and targeting multiple structures are encouraged. A deep brain stimulation (DBS) 'sweet spot' of the striatum for OCD was proposed, and CBT is strongly encouraged. Tourette's patients showed less variance and reliance on treatment optimization. Several DBS targets achieved consistent, rapid, and sustained clinical response. Analysis of fiber connectivity, as opposed to precise neural regions, should be implemented for target selection. Standardization of protocols is necessary to achieve translational outcomes.

BACKGROUND: As distinct from mentally-active sedentary behaviors (e.g. reading), passive sedentary behaviors (e.g. TV-viewing) have been linked to a higher risk of depression, but the underlying mechanisms are unclear. We examined the potential mediating role of sleep problems in prospective relationships of passive sedentary behaviors with major depressive disorder (MDD). METHOD: In 1997, 43 863 adults were surveyed and responses linked to clinician diagnoses of MDD until 2010. The questionnaire included items on sedentary behavior and sleep problems (Karolinska Sleep Questionnaire). Cox proportional hazard models and the 'counterfactual approach' were used to identify potential mediating effects of sleep problems in the association of passive sedentary behavior and MDD. RESULTS: Of the total sample, 3,065 (7.6%) were excluded for having indications of depression at baseline. Of 33,116 participants with complete data (mean age = 51.3 years, SD = 15.7, 64% female); 472 (1.4%) incident cases of MDD were identified during the 13-year follow-up. In Cox regression analyses, higher durations of passive sedentary behavior (≥3 h/day versus <3 h/day) were associated with greater hazards of developing MDD (HR = 1.27; 95% CI = 1.01, 1.58). This relationship remained after adjusting for confounders (HR = 1.29; 95% CI = 1.03, 1.63). Adding sleep problems into the analysis significantly attenuated these relationships (HR = 1.25; 95% CI = 0.99, 1.57). The excess MDD relative risk of passive sedentary behaviors due to sleep problems was statistically significant. LIMITATIONS: Measures of sedentary behavior, physical activity and sleep were self-reported. CONCLUSION: Sleep problems appear to mediate detrimental associations of passive sedentary behavior with depression. Findings require further confirmation using objective measures.

Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, a recently reported autoimmune disorder, can be mistakenly diagnosed as a psychotic disorder, especially schizophrenia, as patients can present with prominent psychotic symptoms, in particular persecutory ideation, hallucinations and disturbed speech. In this study we used machine learning of the clinical data in a large cohort of persons with a positive psychosis history to ascertain whether we could predict NMDAR-positive cases, and which variables most accurately distinguished between NMDAR-positive and -negative cases. Methods SHIP collected nationally representative data from 1825 individuals with a psychotic illness. Plasma samples were available for n=472. To investigate the prevalence of NMDAR autoantibodies a recombinant indirect immunofluorescence test was performed (EuroImmun AG, Lübeck, Germany), with NMDAR transfected human embryonic kidney (HEK) 293 cells quantified using NIS Elements software. NMDAR-positive cases were estimated. Gradient boosting machine learning (the data were randomly split: 60% for initial ascertainment and 40% for validation) was subsequently performed using the clinical data available: 120 variables in total across various domains of sociodemographic, medical history, psychiatric diagnosis and current psychiatric symptoms. Only the variables found to have significant (or near significant) association with being NMDAR-positive were used to develop rules for identifying cases. Results There were 38 NMDAR-positive cases. They were more likely to be associated with a schizophrenia /schizoaffective and a depressive psychosis diagnosis, and less likely to be associated with a bipolar diagnosis, than antibody-negative cases. They were also more likely to be associated with a single episode with good recovery, and with anxiety symptoms and dizziness in the prior 12 months (which included light headedness, feeling faint and unsteady). For the present state sympt

Background Schizophrenia spectrum disorder (SSD) typically presents with a diverse range of cognitive impairments, with the effective treatment of which is advocated as an important future focus for the field. Currently, cognitive remediation therapy (CRT) is the most widely administered form of cognition enhancing treatment, however individual responses to CRT are highly variable in SSD, warranting examination of whether alternative approaches can also enhance cognition. Mindfulness-based interventions (MBI) have shown potential in alleviating the negative impact of clinical SSD symptoms and show promising pro-cognitive treatment effects. The aim of the current study was to retrospectively compare cognitive improvements following two different CRT programs (multi-domain drill and strategy; visually intensive drill and practice) an MBI targeting persistent auditory verbal hallucinations, and a video game-based active control. Methods Data was retrospectively pooled for participants who completed measures of perceptual processing speed, sustained and switching attention, and inhibitory control. Twelve SSD participants completed four weekly one-hour individual sessions of the Individual Mindfulness Program for Voices, 22 completed a minimum of ten one-hour group-/computed-based sessions of the multi-domain drill and strategy intervention COGPACK, 22 completed a minimum of 24 one-hour group-/computer-based sessions of BrainHQ’s (Posit Science) VISUAL Intensive drill and practice intervention, and 17 participants completed a minimum of 10 one-hour group-/computed-based sessions of games putatively similar to exercises common to CRT (active control). Baseline/Post-treatment change effects were calculated for each intervention across specified cognitive variables and converted to standardised Z-scores based on the performance of the active control group. Results Unique and overlapping pro-cognitive effects were identified for each of the three intervention types

Neuroethics is central to the Australian Brain Initiative's aim to sustain a thriving and responsible neurotechnology industry. Diverse and inclusive community and stakeholder engagement and a trans-disciplinary approach to neuroethics will be key to the success of the Australian Brain Initiative.