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Although numerous effective antidepressant (AD) strategies are available for the treatment of major depressive disorder (MDD), many patients do not achieve satisfactory treatment response.
The aims of the present European, cross-sectional, multicenter, naturalistic study were (1) to determine the proportion of patients suffering from primary MDD who received additional psychotherapy to their ongoing psychopharmacotherapy and (2) to identify the associated socio-demographic and clinical patterns.
Patients receiving both treatments were compared to those lacking concomitant additional psychotherapy that was manual-driven psychotherapy (MDP) in all cases.
While 68.8% of a total of 1279 MDD patients received exclusively psychopharmacotherapy, 31.2% underwent a psychopharmacotherapy-MDP combination. The latter patient population was rather younger, higher educated, employed, exhibited an earlier mean age of MDD onset, lower severity of current depressive symptoms with lower odds of suicidality and higher rates of melancholic features, and comorbid asthma and migraine, and was generally treated with lower daily doses of their first-line ADs. Whereas agomelatine was more commonly dispensed in these patients, selective serotonin reuptake inhibitors were more often prescribed in MDD patients lacking additional MDP. No significant between-group differences were detected in terms of treatment outcome.
The fact that the employment of additional MDP was not related to better treatment outcome in MDD represents our major and clinically most relevant finding. Generally, MDP was employed in a minority of our patients who experienced rather beneficial socio-demographic and clinical characteristics. This might reflect an inferior accessibility of these psychotherapeutic techniques for patients who are more severely ill and less socio-economically privileged.
References Bartova L, Fugger G, Dold M, Swoboda MMM, Zohar J, Mendlewicz J, Souery D, Montgomery S, Fabbri C, Serretti A, Kasper S. Combining psychopharmacotherapy and psychotherapy is not associated with better treatment outcome in major depressive disor
Patients with pregnancy-associated secondary brain tumors (PASBT) are challenging to manage. Because no guidelines for the management of such patients currently exist, we performed a systematic review of the literature using PRISMA guidelines with a discussion of management from a neurosurgeon’s perspective.
Systematic review of the literature using PRISMA guidelines from 1999 to 2018.
We identified 301 studies of which 16 publications (22 patients reporting 25 pregnancies, 20 deliveries, 5 early terminations) were suitable for final analysis. The most frequent primary cancers were breast (8/22, 36.36%), skin (6/22, 27.27%), and lung (5/22, 22.73%). Four patients (18.18%) had neurosurgical procedures during their pregnancies. Five patients (22.73%) received neurosurgical resection after their pregnancies. Nine patients (40.91%) received radiation therapy and seven patients (31.82%) received chemotherapy during pregnancy while seven patients (31.82%) received chemotherapy and radiation after pregnancy. There was 1 fetal death (5%) out of 20 healthy deliveries. Five pregnancies (20%) were terminated in the first trimester due to a need for urgent neurosurgical intervention.
Management of PASBT remains a challenging issue. Maternal and fetal risks associated with surgical resection and teratogenicity due to adjuvant therapy should be discussed in the context of a multidisciplinary team. Timing of surgery and the use of systemic chemoradiation depends on the gestational age (GA) of the fetus, extent, and control of the mother’s primary and metastatic disease. Guidelines need to be established to help neuro-oncology teams safely and effectively manage this group of patients.
Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. Since psychopharmacological treatment is thought tc act on the underlying biological basis of the disease, brain imaging techniques enable us to understand the mechanism of action of such compounds. One important tool used to determine patterns of brain dysfunction and how psychopharmacological agents such as antipsychotic compounds work is single-photon emission computerised tomography (SPECT). This technique allows determination of striatal D2 receptor occupancy rates, which are associated with the extrapyramidal side effects (EPS) of antipsychotic drugs. Studies have confirmed that atypical antipsychotic agents have lower occupancy rates than typical agents. No association has been found between D2 receptor occupancy rates n the striatum and antipsychotic efficacy, and it therefore appears that striatal D2 receptor occupancy rates are not necessary for the antipsychotic effect of such agents in schizophrenia. The availability of more refined radioligands will help us not only to understand the action of antipsychotics but also the pathophysiology of schizophrenia.
Pregabalin is indicated for the treatment of GAD in adults in Europe. The efficacy and safety of pregabalin for the treatment of adults and elderly patients with GAD has been demonstrated in 6 of 7 short-term clinical trials of 4 to 8 weeks.
To characterise the long-term efficacy and safety of pregabalin in subjects with GAD.
Subjects were randomised to double-blind treatment with either high-dose pregabalin (450-600 mg/d), low-dose pregabalin (150-300 mg/d), or lorazepam (3-4 mg/d) for 3 months. Treatment was extended with drug or blinded placebo for a further 3 months.
At 3 months, mean change from baseline Hamilton Anxiety Rating Scale (HAM-A) for pregabalin high- and low-dose, and for lorazepam ranged from -16.0 to -17.4. Mean change from baseline Clinical Global Impression-Severity (CGI-S) scores ranged from -2.1 to -2.3 and mean CGI-Improvement (CGI-I) scores were 1.9 for each active treatment group. At 6 months, improvement was retained for all 3 active drug groups, even when switched to placebo. HAM-A and CGI-S change from baseline scores ranged from -14.9 to -19.0 and -2.0 to -2.5, respectively. Mean CGI-I scores ranged from 1.5 to 2.3. The most frequently reported adverse events were insomnia, fatigue, dizziness, headache, and somnolence.
Efficacy was observed at 3 months, with maintained improvement in anxiety symptoms over 6 months of treatment. These results are consistent with previously reported efficacy and safety trials of shorter duration with pregabalin and lorazepam in subjects with GAD.
Dysfunctional neuroplasticity contributes to the pathogenesis of Alzheimer's disease, schizophrenia and depression. However, the underlying molecular mechanisms are not fully understood. Previous studies report neuromodulatory properties of the serotonin-1A (5-HT1A) receptor, which is also altered in these disorders. This suggests 5-HT1A mediated neuroplasticity as potential pathogenic factor.
The aim of this study was to demonstrate 5-HT1A mediated neuroplasticity in vivo.
We used positron emission tomography to quantify 5-HT1A receptor binding (BPND) together with structural magnetic resonance imaging in 35 healthy subjects (mean 26.6 ±6.8 years; 17 women). Voxel-wise regression analysis was performed with gray matter volume (GMV) as dependent and 5-HT1A BPND as independent variable. Additionally, regression analysis was calculated with whole brain GMV as dependent variable and 5-HT1A BPND of the dorsal raphe nucleus (DRN) as independent variable. Control variables were age, sex and total GMV, respectively.
5-HT1A receptor density predicted GMV of the hippocampus, medial temporal cortex, inferior temporal cortex, medial occipital cortex and the pericalcarine region in each hemisphere (p < 0.05 false discovery rate corrected, R2: 0.308–0.503). These associations were independent from local numbers of neurons. Furthermore, 5−HT1A receptor levels in the DRN predicted GMV of the anterior cingulate cortex (p = 0.001, R2=0.656, uncorrected).
These results demonstrate 5-HT1A receptor mediated morphogenetic mechanisms in healthy human subjects' brains, which occur not only locally but also at the macro-network level. Finally, morphogenetic signaling investigated with multimodal neuroimaging could contribute to better understanding and diagnostic identification of gray matter loss in neuropsychiatric disorders.
This position statement will address in an evidence-based approach some of the important issues and controversies of current drug treatment of depression such as the efficacy of antidepressants, their effect on suicidality and their place in a complex psychiatric treatment strategy including psychotherapy. The efficacy of antidepressants is clinically relevant. The highest effect size was demonstrated for severe depression. Based on responder rates and based on double-blind placebo-controlled studies, the number needed to treat (NNT) is 5–7 for acute treatment and four for maintenance treatment. Monotherapy with one drug is often not sufficient and has to be followed by other antidepressants or by comedication/augmentation therapy approaches. Generally, antidepressants reduce suicidality, but under special conditions like young age or personality disorder, they can also increase suicidality. However, under the conditions of good clinical practice, the risk–benefit relationship of treatment with antidepressants can be judged as favourable also in this respect. The capacity of psychiatrists to individualise and optimise treatment decisions in terms of ‘the right drug/treatment for the right patient’ is still restricted since currently there are no sufficient powerful clinical or biological predictors which could help to achieve this goal. There is hope that in future pharmacogenetics will contribute significantly to a personalised treatment. With regard to plasma concentration, therapeutic drug monitoring (TDM) is a useful tool to optimize plasma levels therapeutic outcome. The ideal that all steps of clinical decision-making can be based on the strict rules of evidence-based medicine is far away from reality. Clinical experience so far still has a great impact.
Pregabalin is indicated for the treatment of generalised anxiety disorder (GAD) in adults in Europe. When pregabalin is discontinued, a 1-week (minimum) taper is recommended to prevent potential discontinuation symptoms.
To evaluate whether a 1-week pregabalin taper, after 3 or 6 months of treatment, is associated with the development of discontinuation symptoms (including rebound anxiety) in subjects with GAD.
Subjects were randomised to double-blind treatment with low- (150-300 mg/d) or high-dose pregabalin (450-600 mg/d) or lorazepam (3-4 mg/d) for 3 months. After 3 months ~25% of subjects in each group (per the original randomisation) underwent a double-blind, 1-week taper, with substitution of placebo. The remaining subjects continued on active treatment for another 3 months and underwent the 1-week taper at 6 months.
Discontinuation after 3 months was associated with low mean changes in Physician Withdrawal Checklist (PWC) scores (range: +1.4 to +2.3) and Hamilton Anxiety Rating Scale (HAM A) scores (range: +0.9 to +2.3) for each pregabalin dose and lorazepam. Discontinuation after 6 months was associated with low mean changes in PWC scores (range: -1.0 to +3.0) and HAM A scores (range: -0.8 to +3.0) for all active drugs and placebo. Incidence of rebound anxiety during pregabalin taper was low and did not appear related to treatment dose or duration.
A 1-week taper following 3 or 6 months of pregabalin treatment was not associated with clinically meaningful discontinuation symptoms as evaluated by changes in the PWC and HAM A rating scales.
Most people with bipolar disorder spend a significant percentage of their lifetime experiencing either subsyndromal depressive symptoms or major depressive episodes, which contribute greatly to the high levels of disability and mortality associated with the disorder. Despite the importance of bipolar depression, there are only a small number of recognised treatment options available. Consecutive treatment failures can quickly exhaust these options leading to treatment-resistant bipolar depression (TRBD). Remarkably few studies have evaluated TRBD and those available lack a comprehensive definition of multi-therapy-resistant bipolar depression (MTRBD).
To reach consensus regarding threshold definitions criteria for TRBD and MTRBD.
Based on the evidence of standard treatments available in the latest bipolar disorder treatment guidelines, TRBD and MTRBD criteria were agreed by a representative panel of bipolar disorder experts using a modified Delphi method.
TRBD criteria in bipolar depression was defined as failure to reach sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses, with at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. MTRBD included the same initial definition as TRBD, with the addition of failure of at least one trial with an antidepressant, a psychological treatment and a course of electroconvulsive therapy.
The proposed TRBD and MTRBD criteria may provide an important signpost to help clinicians, researchers and stakeholders in judging how and when to consider new non-standard treatments. However, some challenging diagnostic and therapeutic issues were identified in the consensus process that need further evaluation and research.
Declaration of interest
In the past 3 years, M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Grunbiotics, Glaxo SmithKline, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka, Pfizer and Servier. A.J.C. has in the past 3 years received honoraria for speaking from Astra Zeneca and Lundbeck, honoraria for consulting from Allergan, Janssen, Lundbeck and LivaNova and research grant support from Lundbeck. G.M.G. holds shares in P1Vital and has served as consultant, advisor or CME speaker for Allergan, Angelini, Compass pathways, MSD, Lundbeck, Otsuka, Takeda, Medscape, Minervra, P1Vital, Pfizer, Servier, Shire and Sun Pharma. J.G. has received research funding from National Institute for Health Research, Medical Research Council, Stanley Medical Research Institute and Wellcome. H.G. received grants/research support, consulting fees or honoraria from Gedeon Richter, Genericon, Janssen Cilag, Lundbeck, Otsuka, Pfizer and Servier. R.H.M.-W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, Liva Nova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. R.M. has received research support from Big White Wall, Electromedical Products, Johnson and Johnson, Magstim and P1Vital. S.N. received honoraria from Lundbeck, Jensen and Otsuka. J.C.S. has received funds for research from Alkermes, Pfizer, Allergan, J&J, BMS and been a speaker or consultant for Astellas, Abbott, Sunovion, Sanofi. S.W has, within the past 3 years, attended advisory boards for Sunovion and LivaNova and has undertaken paid lectures for Lundbeck. D.J.S. has received honoraria from Lundbeck. T.S. has reported grants from Pathway Genomics, Stanley Medical Research Institute and Palo Alto Health Sciences; consulting fees from Sunovion Pharamaceuticals Inc.; honoraria from Medscape Education, Global Medical Education and CMEology; and royalties from Jones and Bartlett, UpToDate and Hogrefe Publishing. S.P. has served as a consultant or speaker for Janssen, and Sunovion. P.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. E.V. received grants/ research support, consulting fees or honoraria from Abbott, AB-Biotics, Allergan, Angelini, Dainippon Sumitomo, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka and Sunovion. L.N.Y. has received grants/research support, consulting fees or honoraria from Allergan, Alkermes, Dainippon Sumitomo, Janssen, Lundbeck, Otsuka, Sanofi, Servier, Sunovion, Teva and Valeant. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has also previously received funding for investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth. P.R.A.S. has received research funding support from Corcept Therapeutics Inc. Corcept Therapeutics Inc fully funded attendance at their internal conference in California USA and all related expenses. He has received grant funding from the Medical Research Council UK for a collaborative study with Janssen Research and Development LLC. Janssen Research and Development LLC are providing non-financial contributions to support this study. P.R.A.S. has received a presentation fee from Indivior and an advisory board fee from LivaNova.
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
We compare first-order (refractive) ionospheric effects seen by the MWA with the ionosphere as inferred from GPS data. The first-order ionosphere manifests itself as a bulk position shift of the observed sources across an MWA field of view. These effects can be computed from global ionosphere maps provided by GPS analysis centres, namely the CODE. However, for precision radio astronomy applications, data from local GPS networks needs to be incorporated into ionospheric modelling. For GPS observations, the ionospheric parameters are biased by GPS receiver instrument delays, among other effects, also known as receiver DCBs. The receiver DCBs need to be estimated for any non-CODE GPS station used for ionosphere modelling. In this work, single GPS station-based ionospheric modelling is performed at a time resolution of 10 min. Also the receiver DCBs are estimated for selected Geoscience Australia GPS receivers, located at Murchison Radio Observatory, Yarragadee, Mount Magnet and Wiluna. The ionospheric gradients estimated from GPS are compared with that inferred from MWA. The ionospheric gradients at all the GPS stations show a correlation with the gradients observed with the MWA. The ionosphere estimates obtained using GPS measurements show promise in terms of providing calibration information for the MWA.
GLEAM, the GaLactic and Extragalactic All-sky MWA survey, is a survey of the entire radio sky south of declination + 25° at frequencies between 72 and 231 MHz, made with the MWA using a drift scan method that makes efficient use of the MWA’s very large field-of-view. We present the observation details, imaging strategies, and theoretical sensitivity for GLEAM. The survey ran for two years, the first year using 40-kHz frequency resolution and 0.5-s time resolution; the second year using 10-kHz frequency resolution and 2 s time resolution. The resulting image resolution and sensitivity depends on observing frequency, sky pointing, and image weighting scheme. At 154 MHz, the image resolution is approximately 2.5 × 2.2/cos (δ + 26.7°) arcmin with sensitivity to structures up to ~ 10° in angular size. We provide tables to calculate the expected thermal noise for GLEAM mosaics depending on pointing and frequency and discuss limitations to achieving theoretical noise in Stokes I images. We discuss challenges, and their solutions, that arise for GLEAM including ionospheric effects on source positions and linearly polarised emission, and the instrumental polarisation effects inherent to the MWA’s primary beam.
This work experimentally examines the detachment of liquid droplets from both oleophilic and oleophobic fibres, using an atomic force microscope. The droplet detachment force was found to increase with increasing fibre diameter and forces were higher for philic fibres than phobic fibres. We also considered the detachment of droplets situated on the intersection of two fibres and arrays of fibres (such as found in fibrous mats or filters) and found that the required detachment forces were higher than for similarly sized droplets on a single fibre, though not as high as expected based on theory. A model was developed to predict the detachment force, from single fibres, which agreed well with experimental results. It was found that the entire dataset (single and multiple fibres) could be best described by power law relationships.
The Murchison Widefield Array is a Square Kilometre Array Precursor. The telescope is located at the Murchison Radio–astronomy Observatory in Western Australia. The MWA consists of 4 096 dipoles arranged into 128 dual polarisation aperture arrays forming a connected element interferometer that cross-correlates signals from all 256 inputs. A hybrid approach to the correlation task is employed, with some processing stages being performed by bespoke hardware, based on Field Programmable Gate Arrays, and others by Graphics Processing Units housed in general purpose rack mounted servers. The correlation capability required is approximately 8 tera floating point operations per second. The MWA has commenced operations and the correlator is generating 8.3 TB day−1 of correlation products, that are subsequently transferred 700 km from the MRO to Perth (WA) in real-time for storage and offline processing. In this paper, we outline the correlator design, signal path, and processing elements and present the data format for the internal and external interfaces.