Subjective cognitive changes following premenopausal risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: Women at high risk of ovarian cancer are commonly advised to undergo risk-reducing bilateral salpingo-oophorectomy (BSO) prior to natural menopause. Cognitive symptoms during natural menopause transition are frequently reported; however, very few studies have examined cognitive changes following surgical menopause. To address this gap, we explored the cognitive experiences of women within 24 months post BSO. METHODS: This observational cross-sectional sub-study is part of a larger project, the Early Menopause and Cognition Study (EM-COG). We investigated perceived cognitive experiences in Australian women (n = 16) who underwent risk-reducing BSO using qualitative interviews. Thematic analysis was undertaken to identify key themes. RESULTS: Fifteen out of 16 participants (93.75%) reported changes to cognition within 24 months post BSO. The key cognitive symptoms reported were brain fog, memory and retrieval difficulties, slower processing speed as well as attention difficulties. Five participants (31.3%) experienced negative mood symptoms post BSO. CONCLUSION: Findings from this study suggest that women experience subjective cognitive changes within 24 months post BSO. This period could be a vulnerable time for women's cognitive health. While these findings need to be confirmed by a large prospective study, our research indicates that psychoeducation and awareness will be helpful in managing cognitive symptoms after surgical menopause.

Lipid nanoparticle formulations for optimal RNA-based topical delivery to murine airways.

INTRODUCTION: Lipid nanoparticles (LNP) have been successfully used as a platform technology for delivering nucleic acids to the liver. To broaden the application of LNPs in targeting non-hepatic tissues, we developed LNP-based RNA therapies (siRNA or mRNA) for the respiratory tract. Such optimized LNP systems could offer an early treatment strategy for viral respiratory tract infections such as COVID-19. METHODS: We generated a small library of six LNP formulations with varying helper lipid compositions and characterized their hydrodynamic diameter, size distribution and cargo entrapment properties. Next, we screened these LNP formulations for particle uptake and evaluated their potential for transfecting mRNA encoding green fluorescence protein (GFP) or SARS-CoV2 nucleocapsid-GFP fusion reporter gene in a human airway epithelial cell line in vitro. Following LNP-siGFP delivery, GFP protein knockdown efficiency was assessed by flow cytometry to determine %GFP+ cells and median fluorescence intensity (MFI) for GFP. Finally, lead LNP candidates were validated in Friend leukemia virus B (FVB) male mice via intranasal delivery of an mRNA encoding luciferase, using in vivo bioluminescence imaging. RESULTS: Dynamic light scattering revealed that all LNP formulations contained particles with an average diameter of <100 nm and a polydispersity index of <0.2. Human airway epithelial cell lines in culture internalized LNPs with differential GFP transfection efficiencies (73-97%). The lead formulation LNP6 entrapping GFP or Nuc-GFP mRNA demonstrated the highest transfection efficiency (97%). Administration of LNP-GFP siRNA resulted in a significant reduction of GFP protein expression. For in vivo studies, intranasal delivery of LNPs containing helper lipids (DSPC, DOPC, ESM or DOPS) with luciferase mRNA showed significant increase in luminescence expression in nasal cavity and lungs by at least 10 times above baseline control. CONCLUSION: LNP formulations enable the delivery of RNA payloads into human airway epithelial cells, and in the murine respiratory system; they can be delivered to nasal mucosa and lower respiratory tract via intranasal delivery. The composition of helper lipids in LNPs crucially modulates transfection efficiencies in airway epithelia, highlighting their importance in effective delivery of therapeutic products for airways diseases.

Bazedoxifene - a promising brain active SERM that crosses the blood brain barrier and enhances spatial memory.

Over 20 years of accumulated evidence has shown that the major female sex hormone 17ß-estradiol can enhance cognitive functioning. However, the utility of estradiol as a therapeutic cognitive enhancer is hindered by its unwanted peripheral effects (carcinogenic). Selective estrogen receptor modulators (SERMs) avoid the unwanted effects of estradiol by acting as estrogen receptor antagonists in some tissues such as breast and uterus, but as agonists in others such as bone, and are currently used for the treatment of osteoporosis. However, understanding of their actions in the brain are limited. The third generation SERM bazedoxifene has recently been FDA approved for clinical use with an improved biosafety profile. However, whether bazedoxifene can enter the brain and enhance cognition is unknown. Using mice, the current study aimed to explore if bazedoxifene can 1) cross the blood-brain barrier, 2) rescue ovariectomy-induced hippocampal-dependent spatial memory deficit, and 3) activate neural estrogen response element (ERE)-dependent gene transcription. Using liquid chromatography-mass spectrometry (LC-MS), we firstly demonstrate that a peripheral injection of bazedoxifene can enter the brain. Secondly, we show that an acute intraperitoneal injection of bazedoxifene can rescue ovariectomy-induced spatial memory deficits. And finally, using the ERE-luciferase reporter mouse, we show in vivo that bazedoxifene can activate the ERE in the brain. The evidence shown here suggest bazedoxifene could be a viable cognitive enhancer with promising clinical applicability.

Improvement in depression with oestrogen treatment in women with schizophrenia.

Women with schizophrenia are often noted to suffer with comorbid depression. Many studies have shown associations between fluctuating oestrogen levels in the brain and mental illness. This study investigates the effect of oestradiol treatment on comorbid depressive symptoms in women with schizophrenia. This study is an 8-week, three-arm, double-blind, randomised-controlled trial. The 180 female participants were aged between 18 and 45, with schizophrenia and ongoing symptoms of psychosis Positive and Negative Syndrome Scale (PANSS) score > 60 despite a stable dose of antipsychotic medication. Depressive symptoms were assessed using Montgomery Asberg Depression Scale (MADRS) with a mean score of 73.77 at baseline. Participants received transdermal oestradiol 200 µg or transdermal oestradiol 100 µg or an identical placebo patch. The a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56, but in this study, we focused on the change in MADRS score at the same time points. Data were analysed by using Quade's rank analysis of covariance (ANCOVA) (Huitema 1980) with baseline MADRS score as a covariate. We found a fluctuating but overall trend towards improvement of comorbid depressive symptoms in women with schizophrenia taking transdermal oestrogen 200 mcg compared with oestrogen 100 mcg or placebo. The stronger 'antidepressant' effect of 200 mcg transdermal oestradiol was found at day 28 (p = 0.03). Our study suggests that adjunctive oestradiol treatment for depression may be a promising treatment for women with comorbid depression and schizophrenia.

Coating of PLA-nanoparticles with cyclic, arginine-rich cell penetrating peptides enables oral delivery of liraglutide.

Until today, the oral delivery of peptide drugs is hampered due to their instability in the gastrointestinal tract and low mucosal penetration. To overcome these hurdles, PLA (polylactide acid)-nanoparticles were coated with a cyclic, polyarginine-rich, cell penetrating peptide (cyclic R9-CPP). These surface-modified nanoparticles showed a size and polydispersity index comparable to standard PLA-nanoparticles. The zeta potential showed a significant increase indicating successful CPP-coupling to the surface of the nanoparticles. Cryo-EM micrographs confirmed the appropriate size and morphology of the modified nanoparticles. A high encapsulation efficiency of liraglutide could be achieved. In vitro tests using Caco-2 cells showed high viability indicating the tolerability of this novel formulation. A strongly enhanced mucosal binding and penetration was demonstrated by a Caco-2 binding and uptake assay. In Wistar rats, the novel nanoparticles showed a substantial, 4.5-fold increase in the oral bioavailability of liraglutide revealing great potential for the oral delivery of peptide drugs.

Ionizable amino lipid interactions with POPC: implications for lipid nanoparticle function.

Lipid nanoparticles (LNPs) composed of ionizable cationic lipids are currently the leading systems for siRNA delivery in liver disease, with the major limitation of low siRNA release efficacy into the cytoplasm. Ionizable cationic lipids are known to be of critical importance in LNP structure and stability, siRNA entrapment, and endosomal disruption. However, their distribution inside the LNPs and their exact role in cytoplasmic delivery remain unclear. A recent study [Kulkarni et al., On the formation and morphology of lipid nanoparticles containing ionizable cationic lipids and siRNA, ACS Nano, 2018, 12(5), 4787-4795] on LNP-siRNA systems containing the ionizable lipid DLin-KC2-DMA (also known as KC2 with an apparent pKa of ca. 6.7) suggested that neutral KC2 segregates from other components and forms an amorphous oil droplet in the core of LNPs. In this paper, we present evidence supporting the model proposed by Kulkarni et al. We studied KC2 segregation in the presence of POPC using molecular dynamics simulation, deuterium NMR, SAXS, and cryo-TEM experiments, and found that neutral KC2 has a high tendency to separate from POPC dispersions. KC2 confinement, upon raising the pH during the formulation process, could result in rearrangement of the internal structure of LNPs. As interactions between cationic KC2 and anionic endosomal lipids are thought to be a key factor in cargo release, KC2 confinement inside the LNP may be responsible for the observed low release efficacy.

Raloxifene as a treatment for cognition in women with schizophrenia: the influence of menopause status.

Cognitive impairments cause significant functional issues for people with schizophrenia, often emerging before the onset of hallucinations, delusions and other psychosis symptoms. Current pharmacological treatments do not target cognitive dysfunction. Several lines of evidence support the beneficial effects of estrogens on cognition. Raloxifene hydrochloride, a selective estrogen receptor modulator, has been associated with cognitive improvements in healthy postmenopausal women and in schizophrenia, although findings are inconsistent. Using pooled data from two clinical trials, the aim of the current study was to compare the efficacy of 120 mg/day adjunctive raloxifene to placebo for 12 weeks on cognitive performance in women with schizophrenia who were stratified by menopause status (pre-menopausal; peri-menopausal or post-menopausal). A total of sixty-nine participants with a diagnosis of schizophrenia or schizoaffective disorder were included. Cognition was assessed at baseline and study end using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Results indicated that after stratifying for menopause status (strata) and adjusting for endogenous hormone levels (estrogen, progesterone, follicle stimulating hormone and luteinising hormone), semantic fluency, picture naming and list recognition change from baseline scores for the raloxifene group differed significantly from the placebo group. The findings from the current study highlight the importance of considering menopause status when interpreting the effects of hormonal treatments.

Menstrual cycle irregularity and menopause status influence cognition in women with schizophrenia.

Cognitive impairments are a core feature of schizophrenia and contribute significantly to functional complications. Current pharmacological treatments do not ameliorate cognitive dysfunction and the aetiology of cognitive impairments are poorly understood. Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain and have been suggested to also influence cognition. The aim of the current study was to investigate how HPG axis hormones effect cognition, specifically exploring the influence of menopause status and menstrual cycle irregularity on cognitive performance in women with schizophrenia. The data for the present study represents pooled baseline data from three clinical trials. Two hundred and forty female participants with a diagnosis of schizophrenia or schizoaffective disorder were included in the analysis. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status. Hormone assays for serum sex steroids and pituitary hormones (including estradiol, progesterone, luteinising hormone and follicle-stimulating hormone) were conducted and women were classified as postmenopausal; perimenopausal; premenopausal/reproductive, further classified into regular and irregular menstrual cycles. To model a comparison of cognitive performance for i) perimenopausal; ii) post-menopausal women and iii) reproductive aged women with irregular cycles to reproductive aged women with regular cycles a semiparametric regression model (generalised additive mode) was fitted. The results revealed that in females with schizophrenia, menstrual cycle irregularity predicted significantly poorer cognitive performance in the areas of psychomotor speed, verbal fluency and verbal memory. Perimenopause was not associated with cognitive changes and the post-menopausal period was associated with poorer visuospatial performance. This study provides evidence to associate reproductive hormones with cognitive dysfunction in schizophrenia.

Upper limb activity in myoelectric prosthesis users is biased towards the intact limb and appears unrelated to goal-directed task performance.

Studies of the effectiveness of prosthetic hands involve assessing user performance on functional tasks, typically collected in the lab, sometimes combined with self-report of real-world use. In this paper we compare real-world upper limb activity between a group of 20 myoelectric prosthesis users and 20 anatomically intact adults. Activity was measured from wrist-worn accelerometers over a 7-day period. The temporal patterns in upper limb activity are presented and the balance of activity between the two limbs quantified. We also evaluated the prosthesis users' performance on a goal-directed task, characterised using measures including task success rate, completion time, gaze behaviour patterns, and kinematics (e.g. variability and patterns in hand aperture). Prosthesis users were heavily reliant on their intact limb during everyday life, in contrast to anatomically intact adults who demonstrated similar reliance on both upper limbs. There was no significant correlation between the amount of time a prosthesis was worn and reliance on the intact limb, and there was no significant correlation between either of these measures and any of the assessed kinematic and gaze-related measures of performance. We found participants who had been prescribed a prosthesis for longer to demonstrate more symmetry in their overall upper limb activity, although this was not reflected in the symmetry of unilateral limb use. With the exception of previously published case studies, this is the first report of real world upper limb activity in myoelectric prosthesis users and confirms the widely held belief that users are heavily reliant on their intact limb.

Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia.

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.

Outcome of radical prostatectomy as primary treatment for high-risk prostate cancer patients.

CONTEXT: Recently, there has been considerable interest in the role of radical prostatectomy (RP) in men with high-risk prostate cancer. AIMS: The objective of our study is to report the outcome of upfront RP in our patients with high-risk prostate cancer (Stage ≥ cT2c, a pre-operative serum prostate specific antigen >20 ng/ml or a biopsy Gleason score [GS] 8-10). SUBJECTS AND METHODS: From 1996 to 2010, 208 patients of prostate cancer (high risk category D'Amico's criteria) underwent open RP with bilateral pelvic lymphadenectomy. STATISTICAL ANALYSIS USED: The data was statistically analyzed using Kaplan Meier method and log rank test to calculate progression free, metastasis free survival (MFS) and cancer specific survival (CSS). Furthermore multivariate analysis (MVA) was carried out using SPSS 14 software. (IBM company). RESULTS: At 7 and 10 years, prostate cancer-specific survival (PCSS) was found to be 79.7% and 65%, respectively, biochemical recurrence free survival (BRFS) was 42.4% and 36.7%, respectively and the MFS was 71.1% and 64.4% respectively. High GS was highly predictable of PCSS, BRFS and MFS. Node positivity was the single poor risk factor on MVA whereas biopsy GS, pStage (P = 0.016) and seminal vesicle invasion (P = 0.045) had statistical significance in predicting the MFS. CONCLUSIONS: RP provides accurate pathologic staging of patients with high risk prostate cancer, allows better stratification of patients for further adjuvant therapy and either as an initial approach or part of a multimodal regimen, can provide durable local control and provides excellent CSS.

Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age.

Many women with schizophrenia remain symptomatic despite optimal use of current therapies. While previous studies suggest that adjunctive oestrogen therapy might be effective, large-scale clinical trials are required before clinical applications are possible. This study is the first large-scale randomized-controlled trial in women with treatment-resistant schizophrenia. This Definitive Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized-controlled trial conducted between 2006 and 2011. The 183 female participants were aged between 18 and 45 (mean = 35 years), with schizophrenia or schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication for at least 4 weeks. Mean duration of illness was more than 10 years. Participants received transdermal estradiol 200 µg, transdermal estradiol 100 µg or an identical placebo patch. For the 180 women who completed the study, the a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the Repeatable Battery of Neuropsychological Status. Data were analysed using latent growth curve modelling. Both estradiol groups had greater decreases in PANSS positive, general and total symptoms compared with the placebo group (P<0.01), with a greater effect seen for 200 µg than 100 µg estradiol. The largest effect size was for the positive subscale of PANSS in the estradiol 200 µg treatment group (effect size 0.44, P<0.01). This study shows estradiol is an effective and clinically significant adjunctive therapy for women with treatment-resistant schizophrenia, particularly for positive symptoms.

Quality of life in bipolar and schizoaffective disorder--a naturalistic approach.

PURPOSE: The aim of this study was to evaluate the health-related quality of life (HRQoL) in bipolar type I (BD I) and schizoaffective (SQA) patients during a 2-year period in a naturalistic study. METHODS: This study was based on the data generated by the Bipolar Comprehensive Outcome Study, a prospective, non-interventional, observational study of participants with BD I and SQA disorder. Mixed-Model Repeated Measures Analysis was used to analyze changes in the SF-36 and EQ-5D. RESULTS: Participants exhibited low health status at baseline with SF-36 mean scores of 46.7±10.5 and 36.9±12.9 (best imaginable health=100, normal population≈50) for physical and mental components, respectively. No significant differences were found between the ratings of the BD I and SQA patients on HRQoL. The SF-36 SMC improved significantly over 24 months although SPC scores remained consistent across the study. On the whole, the lowest SMC score was observed among the depressed patients (38.20), followed by the patients with a mixed state (39.01) and the manic patients (39.83). LIMITATIONS: The observational design may have limited the causal relationships and the generalizability within the current findings. CONCLUSIONS: HRQoL was significantly impaired in all stages of BD and SQA when compared to the general population. The impairment of HRQoL was most pronounced in the depressed state, followed by the mixed state and then the manic state. The euthymic patients showed the least impairment. In addition, patients showed a global improvement in their mental health satisfaction over the 2 years follow up period.

Mental health: outcomes of 10 babies of mothers with a history of serious mental illness.

Women with serious mental illness are frequently on antipsychotic medications to maintain their mental health. During pregnancy there is much debate as to whether to continue or cease these medications. The possibility of adverse effects is of concern to clinicians and the women. This study used a case study methodology to identify the outcomes for 10 babies of women with a history of serious mental illness. The results provide further evidence in regard to women and the use of antipsychotic medications throughout pregnancy and during the first year after birth. Separation of mother and baby occurred in five of the 10 babies. This study identifies the neonatal complications for these vulnerable babies as not outside the norm for births in Australia. The high rate of mother-baby separation is of great concern and needs further longitudinal studies.

Serum testosterone levels are related to cognitive function in men with schizophrenia.

BACKGROUND: Sex steroids such as oestrogen and testosterone are potent neurodevelopmental hormones that also play a role in neuromodulation and neuroprotection of the mature brain. Sex steroid hormones may also be involved in the pathophysiology of schizophrenia as reduced circulating sex steroid levels and changes in brain sex steroid receptors are found in people with schizophrenia compared to controls. In men with schizophrenia, recent studies have documented an inverse correlation between serum testosterone and negative symptoms. Our study sought to confirm whether men with schizophrenia had lower levels of testosterone relative to controls and to determine whether lower testosterone levels were related to higher symptom severity and impaired cognition. METHOD: Circulating serum hormone levels (testosterone, oestrogen, and prolactin), cognitive function and symptoms were assessed in 29 chronically ill men with schizophrenia or schizoaffective disorder. Twenty healthy men were recruited as a comparison group. A series of regression analyses were performed to determine the extent to which circulating sex steroid hormone levels predict cognition and symptoms in men with schizophrenia. RESULTS: We did not find a significant difference in serum testosterone levels between groups. However, circulating testosterone levels significantly predicted performance on verbal memory, processing speed, and working memory in men with schizophrenia. With the exception of an effect of oestrogen on verbal memory, circulating sex steroid levels did not predict cognitive function in healthy men. Testosterone levels were not related to positive or negative symptom severity, but testosterone influenced excitement/hostility levels in our schizophrenia sample. CONCLUSIONS: The results suggest that circulating sex steroids may modulate cognitive deficits associated with schizophrenia.

Vertical profiles of black carbon aerosols over the urban locations in South India.

Vertical profiles of black carbon (BC) aerosol were determined from aircraft measurements under the Cloud Aerosol Interaction and Precipitation Enhancement Experiment (CAIPEEX) program conducted by the Indian Institute of Tropical Meteorology, India during 2009 over Bangalore and Hyderabad in south India. BC mass loadings decreased approximately monotonically from 10(3) to 10(4) ng/m(3) at the surface to ~10(2) ng/m(3) at an altitude of about 7 km; although layers at intermediate levels containing anomalously high BC loadings were frequently encountered that were attributed mainly to the convective transport from surface sources accompanied by changes in the local boundary layer and atmospheric stability. In addition, as evidenced from air mass back trajectories; long range transport from distant sources contributed to some anomalous spikes in BC concentration. The presence of BC in cloud forming regions of the free troposphere could have important implications for cloud microphysics and subsequent rainfall mechanism over this region. Apart from this, the effects on human health are equally important.

Disambiguating ventral striatum fMRI-related BOLD signal during reward prediction in schizophrenia.

Reward detection, surprise detection and prediction-error signaling have all been proposed as roles for the ventral striatum (vStr). Previous neuroimaging studies of striatal function in schizophrenia have found attenuated neural responses to reward-related prediction errors; however, as prediction errors represent a discrepancy in mesolimbic neural activity between expected and actual events, it is critical to examine responses to both expected and unexpected rewards (URs) in conjunction with expected and UR omissions in order to clarify the nature of ventral striatal dysfunction in schizophrenia. In the present study, healthy adults and people with schizophrenia were tested with a reward-related prediction-error task during functional magnetic resonance imaging to determine whether schizophrenia is associated with altered neural responses in the vStr to rewards, surprise prediction errors or all three factors. In healthy adults, we found neural responses in the vStr were correlated more specifically with prediction errors than to surprising events or reward stimuli alone. People with schizophrenia did not display the normal differential activation between expected and URs, which was partially due to exaggerated ventral striatal responses to expected rewards (right vStr) but also included blunted responses to unexpected outcomes (left vStr). This finding shows that neural responses, which typically are elicited by surprise, can also occur to well-predicted events in schizophrenia and identifies aberrant activity in the vStr as a key node of dysfunction in the neural circuitry used to differentiate expected and unexpected feedback in schizophrenia.

Antipsychotics in pregnancy.

Women who are pregnant and who have a history of psychosis are commonly managed with antipsychotic medications. The evidence regarding the use of antipsychotics in pregnancy has been insufficient to provide adequate support for this practice and is a concern for clinicians and women alike. This review presents literature surrounding the use of antipsychotic medications in pregnancy, providing an overview of the historical and contemporary perspectives which influence clinicians prescribing practices. Data were sourced from Medline, CINAHL, PsycINFo, using the terms antipsychotics with pregnancy and psychosis or schizophrenia. This was expanded to include the most common atypical antipsychotics: olanzapine, risperidone, clozapine, quetiapine, ziprasidone and aripiprazole. Literature was found reporting the use of antipsychotic medications in pregnancy since the introduction of antipsychotics in the 1950s, comprising mainly of authors' reviews of the literature, case studies, retrospective reports, drug company registries and more recently a prospective comparative study. This review identifies that the literature provides no clear answer for clinicians as to the risk associated with the use of antipsychotics in pregnancy. To this effect, recently in Australia, the National Register of Antipsychotic Medications in Pregnancy was established to prospectively collect information regarding outcomes for mother and baby, when antipsychotic medications have been used during pregnancy.

A prospective study of the impact of subthreshold mixed states on the 24-month clinical outcomes of bipolar I disorder or schizoaffective disorder.

OBJECTIVES: The clinical significance of subthreshold mixed states is unclear. This study investigated the clinical outcomes in participants with bipolar I disorder or schizoaffective disorder, using the Cassidy and Benazzi criteria for manic and depressive mixed states, respectively. METHODS: Participants (N=239) in a prospective observational study of treatment and outcomes in bipolar I or schizoaffective disorder, bipolar type, were grouped based on study entry clinical presentation as having pure depression (n=63) if they satisfied DSM-IV-TR criteria for a Major Depressive Episode (MDE), depressive mixed state if they also had at least three concurrent hypomanic symptoms (n=33), or not depressed (n=143) if they did not satisfy the criteria for MDE. Participants were similarly grouped as having pure mania (n=3) if they satisfied DSM-IV criteria for a Manic Episode, manic mixed state if they also had at least two concurrent depressive symptoms (n=33), or not manic (n=203). Clinical data were collected by interview every 3 months over a 24-month period. RESULTS: Measures of quality of life, mental and physical health over the 24-month period were significantly worse for participants who were classified as having mixed states at study entry on most outcome measures compared to participants who were not in an illness episode at study entry. A depressive mixed state was predictive of greater manic symptomatology over the 24 months compared to participants with pure depression. CONCLUSION: In participants with a current episode of mood disorder, the presence of subthreshold symptoms of opposite polarity was associated with poorer clinical outcomes over a 24-month period.

Effects of rTMS on an auditory oddball task: a pilot study of cortical plasticity and the EEG.

The objective of this study was to explore the effects of 1Hz repetitive transcranial magnetic stimulation (rTMS) applied to dorsal lateral prefrontal cortex (DLPFC) on both an EEG index of cortical excitation and inhibition, event-related desynchronization/ synchronization (ERDIS) and on the P300 component of an auditory oddball-induced ERP. Eight normal participants received 15 minutes of 1Hz rTMS at 110% of the resting motor threshold to right DLPFC. ERDIS of alpha and beta bands was measured during an auditory oddball task immediately before and after stimulation. There was significantly less alpha desynchronization post-TMS, and this effect was widespread excepting posterior midline sites. No changes were found to oddball-P300 amplitudes or latencies. In conclusion, the findings of less alpha desynchronization post-TMS are compatible with notions of slow rTMS causing a decrease in cortical excitation.