The relationship between cognitive clusters and telomere length in bipolar-schizophrenia spectrum disorders.

BACKGROUND: Schizophrenia and bipolar disorder are complex mental illnesses that are associated with cognitive deficits. There is considerable cognitive heterogeneity that exists within both disorders. Studies that cluster schizophrenia and bipolar patients into subgroups based on their cognitive profile increasingly demonstrate that, relative to healthy controls, there is a severely compromised subgroup and a relatively intact subgroup. There is emerging evidence that telomere shortening, a marker of cellular senescence, may be associated with cognitive impairments. The aim of this study was to explore the relationship between cognitive subgroups in bipolar-schizophrenia spectrum disorders and telomere length against a healthy control sample. METHODS: Participants included a transdiagnostic group diagnosed with bipolar, schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 113). Cognitive clusters within the transdiagnostic patient group, were determined using K-means cluster analysis based on current cognitive functioning (MATRICS Consensus Cognitive Battery scores). Telomere length was determined using quantitative PCRs genomic DNA extracted from whole blood. Emergent clusters were then compared to the healthy control group on telomere length. RESULTS: Two clusters emerged within the patient group that were deemed to reflect a relatively intact cognitive group and a cognitively impaired subgroup. Telomere length was significantly shorter in the severely impaired cognitive subgroup compared to the healthy control group. CONCLUSIONS: This study replicates previous findings of transdiagnostic cognitive subgroups and associates shorter telomere length with the severely impaired cognitive subgroup. These findings support emerging literature associating cognitive impairments in psychiatric disorders to accelerated cellular aging as indexed by telomere length.

Influence of cortisol awakening response on telomere length: Trends for males and females.

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.

Collective pause: improving staff performance in acute medicine through a brief mindfulness-based group programme.

BACKGROUND: Hospital wards are a complex and dynamic environment that rely on optimal staff performance. However, there is little research evaluating group interventions to improve staff attention and teamwork. AIMS: To evaluate whether a regular, short and guided group mindfulness practice for staff in an acute general medicine team improves attention and teamwork. METHODS: A 10-min programme comprising mindfulness exercises and techniques was delivered daily to a multidisciplinary general medicine team based in a tertiary hospital for 4 weeks. This was undertaken immediately prior to the team's interdisciplinary ward round. We used a mixed-method design, with self-rated surveys to measure mindfulness and staff perception of hospital safety culture, and a focus group to understand participants' experiences. We estimated mean differences using Kruskal-Wallis tests across 10 time-points and thematically analysed recorded transcripts. RESULTS: There was an increase in staff attention to the team meeting as measured by the decentering domain across time (P < 0.001). There was a trend to greater staff openness with a non-significant increase in curiosity (P = 0.14). We identified two overarching qualitative themes: feasibility of the programme and impact on staff and workplace. The programme was a calming circuit breaker to staff's day, which aided in feeling more connected to the group and subjectively better ward round experience. The logistics of the programme, including timing, and the facilitator developing trust with the participants, appear important in implementation. CONCLUSION: A brief mindfulness-based intervention delivered to a general medical team improves staff attention at a multidisciplinary team meeting and team functioning.

A network meta-analysis of stress mediators in suicide behaviour.

Stress homeostatic mediators are the most consistently anomalous biomarkers observed in suicide and may therefore point to a common 'core biology' of stress susceptibility, and suicidal behaviour. Previously reported meta-analyses have demonstrated aberrant levels of stress cortisol and inflammatory cytokines in suicide patients compared to controls, and significant associations between the stress regulator FK506-binding protein 51 (FKBP5) gene and suicidal behaviour. Although these independent studies were investigated as separate entities in suicide, stress mediators interact in a dynamic system, collectively giving rise to system changes physiologically, and ultimately psychologically and behaviourally. It is therefore important to study the dynamic network these stress mediators. Network meta-analysis allows for the simultaneous comparison of more than two biological mediators, and for comparisons to be made between mediators that have not been directly compared before, using previously reported, pooled meta data. Such network approaches may help study the complex biological phenomena of suicide and may provide better prediction of biological risk of suicidal states. METHODS: This study aimed to establish the comparative relationships between key stress mediators in suicidal patients compared to non-suicidal controls using a random-effects network meta-analysis approach.. The key stress mediators included cortisol, six inflammatory markers (interleukin-6 (IL-6), interleukin-4 (IL-4), interleukin-2 (IL-2), tumour necrosis factor-a (TNF-α), interferon (IFN-y) and transforming growth factor ß (TGF-ß), and the FKBP5 single nucleotide polymorphism (SNP) allele. Data was derived from three previously published meta-analysis. The study population comprised of 1348 suicidal patients, defined as suicide attempters, completers, or patients with severe suicidal ideation, and 1750 non-suicidal controls, defined as healthy controls and psychiatric patients without suicidal ideation or previous attempts. RESULTS: Pair-wise indirect effects of stress mediators in suicide compared to controls demonstrated that relative to the effect of the FKBP5 risk SNP allele on suicide risk, the magnitude of differences (suicide vs control) for the levels of IL-2 (SMD -0.72; 95% CI, -0.135 to -0.09 and IL-4 (SMD -0.71; 95% CI, -1.34 to -0.08) were significantly smaller (with 95% confidence intervals not crossing the null). The comparative relationships between stress mediators in suicidal behaviour demonstrates that the dynamic stress network relationship is dysregulated in suicide patients when compared to controls. CONCLUSIONS: This model suggests that a genetic stress susceptibility with downstream abnormal cortisol stress axis functioning, together with anomalous interactions between the inflammatory system, may be one of the neurobiological correlates of suicide behaviour. This biological state may leave the individual physiologically susceptible and unable to cope with environmental stressors, which is consistent with the stress-diathesis hypothesis of suicide behaviour.

Serum estradiol as a blood-based biomarker predicting hormonal treatment outcomes in women with schizophrenia.

Patients diagnosed with schizophrenia display substantial heterogeneity in terms of their clinical presentations, and treatment response. Accumulating research suggests that such high diversity may reflect distinct biological subtypes with differentially affected underlying neurobiology. Novel treatments, including sex hormone estradiol treatments, provide alternative efficacious treatment avenues but also should be studied within the context of potential heterogeneity. This repeated-measures study characterised the association between hormone levels (estrogen, progesterone, testosterone, prolactin, FSH, LH, DHEA) and symptom treatment outcomes (defined by The Positive and Negative Syndrome Scale (PANSS)) across a 56-day study of 200 ug adjunctive estradiol treatment in women with schizophrenia. Group-based trajectory models was used to account for potential heterogeneity (subgroups). Receiver operating characteristic (ROC) curves were evaluated to define the predictive value of endogenous estradiol levels as a treatment-response biomarker of estradiol treatment. The results generated two subgroups; a treatment-responder group who demonstrated decreasing PANSS scores across time, and a treatment non-responder group, demonstrating stable PANSS scores across time. The treatment-responder subgroup was significantly negatively predicted by estradiol blood level (b= -2.34, SE= 1.17, p = 0.047), while FSH blood level was positively associated with the treatment non-responders (b= 7.14, SE= 2.54, p = 0.008). ROC for day 28, 56 time points yielded area under the curve of 0.52 and 0.55, respectively. Harrell's C-statistic = 0.59. This is the first study to identify endocrine markers in blood serum predicting response to estradiol treatment in female schizophrenia patients, highlighting the existence of heterogeneity of response, indicative of molecular subtypes. Characterising the differential underlying biology of the subgroups may lead to better targeted, specific treatments in the future.(ClinicalTrials.gov Identifier: NCT00357006). https://www.clinicaltrials.gov/ct2/show/NCT00357006.

Coping styles and mental health in response to societal changes during the COVID-19 pandemic.

BACKGROUND: Psychosocial responses to infectious disease outbreaks have the potential to inflict acute and longstanding mental health consequences. Early research across the globe has found wide ranging psychological responses to the current COVID-19 pandemic. Understanding how different coping styles can be effective in mitigating mental ill health would enable better tailored psychological support. AIMS: The aim of this study was to gain an understanding of psychosocial responses to the COVID-19 pandemic, including depression, anxiety and distress, as well as effective coping styles in an Australian sample. METHOD: A sample of 1,495 adults, residing in Australia between April 3rd and May 3rd 2020, completed an online survey which measured psychological distress (Impact of Events Scale-Revised), depression, anxiety, stress (DASS-21), as well as coping strategies (Brief COPE). RESULTS: 47% of the respondents were experiencing some degree of psychological distress. Females experienced higher levels of depression, anxiety and stress than males. Coping strategies associated with better mental health were positive reframing, acceptance and humour. Conversely, self-blame, venting, behavioural disengagement and self-distraction were associated with poorer mental health. CONCLUSION: Rates of psychological symptoms amongst the Australian population are similar to those reported in other countries. Findings add to the growing literature demonstrating a gender disparity in the mental health impacts of COVID-19. Positive emotion focused coping strategies may be effective for reducing psychological symptoms. Understanding psychosocial responses including beneficial coping strategies are crucial to manage the current COVID-19 situation optimally, as well as to develop mental health response plans for future pandemics.

Efficacy, efficiency and safety of high-frequency repetitive transcranial magnetic stimulation applied more than once a day in depression: A systematic review.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression but a standard course can be time-consuming. Of all rTMS protocols, high-frequency rTMS (HF rTMS) is the most studied and applied in clinical settings. Little is known about applying multiple sessions of HF rTMS per day, in so-called accelerated schedules. METHODS: We systematically searched electronic records up to September 2019 for studies that applied HF rTMS in accelerated schedules to treat depression to review its efficacy, efficiency and safety. Treatment effect sizes of accelerated rTMS versus standard and sham rTMS were calculated from comparison studies and pooled to derive overall treatment effect. RESULTS: Of 1,361 records screened, 12 met review criteria. Qualitative synthesis suggested accelerated HF rTMS was equally effective as once-daily scheduling in treating depression. It is equivocal if accelerated HF rTMS results in more rapid antidepressant response. Accelerated HF rTMS was well-tolerated. The small number of studies suitable for quantitative analysis led to pooled effect sizes that did not reach statistical significance. LIMITATIONS: There was an overall paucity of studies examining the accelerated application of HF rTMS and even fewer studies comparing accelerated HF rTMS with once-daily or sham rTMS. CONCLUSION: Our review found comparable antidepressant efficacy between accelerated and once-daily HF rTMS. Between group differences in therapeutic effect sizes were not clinically meaningful. More studies investigating accelerated rTMS protocols are needed to validate its utility and guide clinical decision making.

Effects of Oral Contraceptive Androgenicity on Visuospatial and Social-Emotional Cognition: A Prospective Observational Trial.

Oral contraceptives (OCs) containing estrogen and progesterone analogues are widely used amongst reproductive-aged women, but their neurocognitive impact is poorly understood. Preliminary studies suggest that OCs improve verbal memory and that OCs with greater androgenic activity may improve visuospatial ability. We sought to explore the cognitive impact of OCs by assessing performance of OC users at different stages of the OC cycle, and comparing this performance between users of different OC formulations according to known androgenic activity. We conducted a prospective, observational trial of OC users, evaluating cognitive performance with CogState software on two occasions: days 7-10 of active hormonal pill phase, and days 3-5 of the inactive pill phase (coinciding with the withdrawal bleed resembling menstruation). Thirty-five OC users (18 taking androgenic formulations, 17 taking anti-androgenic) were assessed. Analysis by androgenic activity showed superior performance by users of androgenic OCs, as compared to anti-androgenic OCs, in visuospatial ability and facial affect discrimination tasks. A growing understanding of cognitive effects of OC progestin androgenicity may have implications in choice of OC formulation for individuals and in future OC development.

Investigating high- and low-frequency neuro-cardiac-guided TMS for probing the frontal vagal pathway.

BACKGROUND: Investigating approaches for determining a functionally meaningful dorsolateral prefrontal cortex (DLPFC) stimulation site is imperative for optimising repetitive transcranial magnetic stimulation (rTMS) response rates for treatment-resistant depression. One proposed approach is neuro-cardiac-guided rTMS (NCG-TMS) in which high frequency rTMS is applied to the DLPFC to determine the site of greatest heart rate deceleration. This site is thought to index a frontal-vagal autonomic pathway that intersects a key pathway believed to underlie rTMS response. OBJECTIVE: We aimed to independently replicate previous findings of high-frequency NCG-TMS and extend it to evaluate the use of low-frequency rTMS for NCG-TMS. METHODS: Twenty healthy participants (13 female; aged 38.6 ± 13.9) underwent NCG-TMS on frontal, fronto-central (active) and central (control) sites. For high-frequency NCG-TMS, three 5 s trains of 10 Hz were provided at each left hemisphere site. For low-frequency NCG-TMS, 60 s trains of 1 Hz were applied to left and right hemispheres and heart rate and heart rate variability outcome measures were analysed. RESULTS: For high-frequency NCG-TMS, heart rate deceleration was observed at the left frontal compared with the central site. For low-frequency NCG-TMS, accelerated heart rate was found at the right frontal compared with central sites. No other site differences were observed. CONCLUSION: Opposite patterns of heart rate activity were found for high- and low-frequency NCG-TMS. The high-frequency NCG-TMS data replicate previous findings and support further investigations on the clinical utility of NCG-TMS for optimising rTMS site localisation. Further work assessing the value of low-frequency NCG-TMS for rTMS site localisation is warranted.

Do Genital Cosmetic Procedures Improve Women's Self-Esteem? A Systematic Review and Meta-Analysis.

BACKGROUND: The popularity of genital cosmetic procedures in women is increasing. These procedures are often assumed and promoted as having a positive effect on women's psychological well-being, particularly their self-esteem. Empirical support for these claims is lacking. OBJECTIVES: The aim of this study was to conduct a systematic review and meta-analysis of the impact of genital cosmetic procedures on self-esteem in women. METHODS: The authors performed a systematic literature review of MEDLINE, PreMEDLINE, Ebase, EMBASE, OVID, CINAHL, Cochrane, PsycINFO, and PubMed to identify articles that measured self-esteem in women after a genital cosmetic procedure. A meta-analysis was conducted to assess the pooled effect of these procedures on self-esteem. RESULTS: The authors identified 5 eligible studies for the meta-analysis, comprising 2 prospective and 3 retrospective studies. Labia minora reduction was the most commonly studied procedure. All 5 studies used different measures of self-esteem, with only 1 study employing a validated psychometric measure at both preoperative and postoperative time points. The meta-analysis results showed a pooled logit rate estimate of 1.230, indicating a positive effect of surgery on self-esteem. However, there was substantial heterogeneity across studies. CONCLUSIONS: Female genital cosmetic procedures, particularly labiaplasty, appear to have a positive effect on women's self-esteem. However, inconsistencies in study measures and methods limit our conclusions. Future research should involve the development of standardized outcome measures to more accurately assess the impact of these procedures on self-esteem, and on psychological well-being more generally.

Delirium misdiagnosis risk in psychiatry: a machine learning-logistic regression predictive algorithm.

BACKGROUND: Delirium is a frequent diagnosis made by Consultation-Liaison Psychiatry (CLP). Numerous studies have demonstrated misdiagnosis prior to referral to CLP. Few studies have considered the factors underlying misdiagnosis using multivariate approaches. OBJECTIVES: To determine the number of cases referred to CLP, which are misdiagnosed at time of referral, to build an accurate predictive classifier algorithm, using input variables related to delirium misdiagnosis. METHOD: A retrospective observational study was conducted at Alfred Hospital in Melbourne, collecting data from a record of all patients seen by CLP for a period of 5 months. Data was collected pertaining to putative factors underlying misdiagnosis. A Machine Learning-Logistic Regression classifier model was built, to classify cases of accurate delirium diagnosis vs. misdiagnosis. RESULTS: Thirty five of 74 new cases referred were misdiagnosed. The proposed predictive algorithm achieved a mean Receiver Operating Characteristic (ROC) Area under the curve (AUC) of 79%, an average 72% classification accuracy, 77% sensitivity and 67% specificity. CONCLUSIONS: Delirium is commonly misdiagnosed in hospital settings. Our findings support the potential application of Machine Leaning-logistic predictive classifier in health care settings.

Peak saccadic eye velocity across menstrual phases in naturally cycling women; A pilot study.

Peak saccadic eye velocity (pSEV) has been investigated in studies that characterise the pathophysiology of menstrual cycle related mood disorders, such as premenstrual dysphoric disorder (PMDD). pSEV is a stable and sensitive measure of gamma-aminobutyric acid A (GABAA) receptor function. Dysregulation of the GABA pathway has been associated with the onset of PMDD. Despite a growing number of studies utilising pSEV as an outcome measure in interventional drug studies for menstrual cycle related mood disorders, there are no reported studies that have investigated whether pSEV is sensitive to hormone fluctuations across the natural menstrual cycle. To address this gap, this pilot study aimed to characterise pSEV in women across the menstrual cycle. Participants were monitored across two menstrual cycles and saccadic eye movements were measured in both luteal and follicular phases. Seven participants completed the full study and were included in the final analysis. Results revealed luteal phase pSEV was significantly less than follicular phase pSEV. This finding is novel and forms a stepping-stone for further understanding the associations between menstrual hormone profiles and GABAA receptors.

Dissecting the syndrome of schizophrenia: Associations between symptomatology and hormone levels in women with schizophrenia.

Despite many studies implicating reproductive hormones in the development and outcome of schizophrenia, few have characterised the association between symptomatology and hormonal trajectories. To understand the influence of hormones on schizophrenia symptoms, serum steroids (estradiol, progesterone, follicular stimulating hormone (FSH), luteinising hormone (LH), and dehydroepiandrosterone (DHEA)) and psychopathology (The positive-and-negative-syndrome-scale(PANSS)) and depression (Montgomery-Asberg-Depression-Rating Scale(MADRS)) were collected across 12-weeks in 45 women (mean age 46) diagnosed with schizophrenia. To account for potential heterogeneity, Group-based-trajectory-modelling of psychopathology was used to identify distinct subgroups of individuals following a similar pattern of association between symptom score and hormone levels over-time. Two trajectories were identified for PANSS: one subgroup with lower symptom severity was associated with FSH, DHEA, LH, and another high severity subgroup associated with LH. Two trajectories were identified for MADRS: 'depressed' (associated with FSH), and non-depressed. The result delineates subpopulations with unique psychopathology and hormone associations that support the hypothesis that reproductive hormones play a role in the pathophysiology of schizophrenia, and that heterogeneity may exist in hormonal sensitivities in the schizophrenia population. Stratification of subjects according to biological phenotype may help improve existing treatments through personalised-medicine strategies. The endocrine system may be one such biological mechanism to continue dissecting the syndrome.

Mindfulness-based intervention to reduce burnout and psychological distress, and improve wellbeing in psychiatry trainees: a pilot study.

BACKGROUND: Healthcare professionals including psychiatry trainees experience high amounts of occupational stress. This pilot study aims to assess the impacts and feasibility of a mindfulness-based intervention program as an occupational intervention in a metropolitan hospital. METHOD: Psychiatry trainees participated in an mindfulness-based intervention training program consisting of 1-h weekly sessions over 8 weeks. Levels of psychological distress and mindfulness were measured pre and post-intervention. Qualitative data through an open-ended feedback survey were also collected. RESULTS: There was an improved level of mindfulness and a decreased level of burnout among trainees post-intervention. Advantages of the program included having a compassionate facilitator and the program being tailored to healthcare staff. Limiting factors included time restraints and clinical responsibilities. CONCLUSION: Psychiatry trainees can benefit from an occupational MBI program. This can positively impact their health as well as improve their work performance. A number of factors important for implementation of a mindfulness-based intervention program were also identified.

Is rTMS effective for anxiety symptoms in major depressive disorder? An efficacy analysis comparing left-sided high-frequency, right-sided low-frequency, and sequential bilateral rTMS protocols.

BACKGROUND: Anxiety symptoms are common in major depressive disorder. Whilst therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression is well-established, minimal research has investigated rTMS's efficacy in treating anxiety symptoms in depression. METHODS: This study investigates the effectiveness of rTMS in treating anxiety symptoms in depression, specifically the relative efficacy of the three rTMS protocols commonly used in clinical practice: left-sided high-frequency, right-sided low-frequency and sequential bilateral rTMS. Antidepressant efficacy of each rTMS protocol is also investigated. Treatment data for 697 patients were pooled from three studies across five sites. Changes in Beck's Anxiety Inventory (BAI) and the Hamilton Depression Rating Scale over 4-week rTMS courses were analysed using latent growth curve modelling. RESULTS: All rTMS protocols were effective in treating anxiety symptoms (mean BAI reduction, 8.13 points; p < 0.001) and depressive symptoms. Near therapeutic equivalence was seen across the three protocols. Improvement in depressive severity positively correlated with improvement in anxiety. Both high- and low-baseline anxiety scores showed overall symptom reduction. CONCLUSIONS: This study addresses the clinical knowledge gap pertaining to rTMS's therapeutic efficacy in treating anxiety symptoms in depression and the relative efficacy of three commonly used stimulation protocols. Our findings suggest therapeutic equivalence across left-sided high-frequency, right-sided low-frequency, and sequential bilateral rTMS approaches.