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Symptoms of anxiety and depression often coexist, and evidence suggests that this has a genetic basis, among other possible causes. However, the current classification of comorbid generalised anxiety disorder (GAD) and depression (anxious depression) in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition; DSM-5) does not fully reflect the high prevalence of anxiety symptoms in people with depression and the International Classification of Diseases (10th and 11th revisions) has tended to identify anxious depression with minor disorders seen in primary care. As a result, few dedicated therapeutic trials have been conducted in patients with anxious depression, and specific treatment guidelines and recommendations are lacking. Fortunately, there is considerable therapeutic overlap between anxiety and depression, such that many agents with antidepressant efficacy are also effective for symptoms of GAD. The initial treatment of a patient with depression and symptoms of anxiety should be with an agent that is approved for both major depressive disorder and GAD, such as a selective serotonin reuptake inhibitor. There is an obvious need for greater recognition of anxious depression in order to boost the volume of high-quality clinical data, which should translate over time into better, more specific treatment recommendations and improved outcomes.

This narrative review summarizes and discusses the implications of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and the upcoming International Classification of Diseases (ICD)-11 classification systems on the prevalence of bipolar disorder and on the validity of the DSM-5 diagnosis of bipolar disorder according to the Robin and Guze criteria of diagnostic validity. Here we review and discuss current data on the prevalence of bipolar disorder diagnosed according to DSM-5 versus DSM-IV, and data on characteristics of bipolar disorder in the two diagnostic systems in relation to extended Robin and Guze criteria: 1) clinical presentation, 2) associations with para-clinical data such as brain imaging and blood-based biomarkers, 3) delimitation from other disorders, 4) associations with family history / genetics, 5) prognosis and long-term follow-up, and 6) treatment effects. The review highlights that few studies have investigated consequences for the prevalence of the diagnosis of bipolar disorder and for the validity of the diagnosis. Findings from these studies suggest a substantial decrease in the point prevalence of a diagnosis of bipolar with DSM-5 compared with DSM-IV, ranging from 30-50%, but a smaller decrease in the prevalence during lifetime, corresponding to a 6% reduction. It is concluded that it is likely that the use of DSM-5 and ICD-11 will result in diagnostic delay and delayed early intervention in bipolar disorder. Finally, we recommend areas for future research. (c) 2021 Elsevier B.V. and ECNP. All rights reserved.

Background Bipolar disorder (BD) is associated with excess and premature cardiovascular mortality. Elevated blood pressure (BP) is a leading contributor to cardiovascular risk. However, few studies have examined BP in BD in comparison to other psychiatric disorders. Furthermore, the association between BP and mood instability is not presently clear despite increasing interest in repurposing existing antihypertensive medications as possible novel BD treatments. Thus we examined BP differences between BD and borderline personality disorder (BPD), a disorder with a similar symptom profile through chronic mood instability. Methods A total of 106 adults (38 BD, 25 BPD, and 43 healthy controls), evaluated in the Automated Monitoring of Symptom Severity (AMoSS) study, completed a week-long home blood pressure monitoring assessment and ecological momentary assessment of mood. We examined group-wise differences in mean BP and BP variability and their association with mood instability. Results BD individuals had a significantly wider resting pulse pressure (40.8 ± 7.4, mmHg) compared to BPD (35.7 ± 5.3, mmHg, P = 0.03) and control participants (37.3 ± 6.3, mmHg, P = 0.036). Systolic BP was negatively associated with sad mood instability, and all measures of mean BP (systolic, diastolic, and mean arterial pressure) were negatively associated with positive mood instability. Conclusions This study demonstrates BP differences between BD and healthy and clinical controls that are within a normotensive range. Early pulse pressure widening may be a modifiable pathophysiological feature of BD that confers later cardiovascular risk. BP may be an important transdiagnostic predictor of mood instability and a potential explicit treatment target.

Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and outcome. This may be due to a high prevalence of somatic comorbidities and an increased risk of delays in and poorer treatment of somatic disease in patients with severe mental illness in general. Vaccination is the most important public health intervention to tackle the ongoing pandemic. We undertook a systematic review regarding the data on vaccinations in individuals with BD. Proportion of prevalence rates, efficacy and specific side effects of vaccinations and in individuals with BD were searched. Results show that only five studies have investigated vaccinations in individuals with BD, which substantially limits the interpretation of overall findings. Studies on antibody production after vaccinations in BD are very limited and results are inconsistent. Also, the evidence-based science on side effects of vaccinations in individuals with BD so far is poor. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

BackgroundDepressed patients often focus on negative life events. Effective antidepressant therapy reverses this negative emotional bias (NEB) within 1 week. Clinical therapeutic effect usually requires 4–6 weeks. The value of implementing NEB monitoring for the personalisation of antidepressant therapy is unknown.ObjectiveTo estimate the likely outcome and cost consequences of adopting the P1vital Oxford Emotional Test Battery (ETB) for this purpose in routine primary care in England.MethodsA hybrid decision analytic model (decision tree plus Markov model) was developed to estimate the cost-effectiveness of ETB monitoring versus no ETB over 52 weeks using quality-adjusted life years (QALYs). Differences in depression severity, episode type and analytical perspectives were considered. Input data were derived from relevant guidelines, literature, national databases, expert opinion and the developers for the year 2013. Multiple sensitivity analyses addressed uncertainty.FindingsThe mean number of ETB tests is 2.162 per newly diagnosed patient and 2.166 per patient with recurrent depression. The incremental cost-effectiveness of ETB versus ‘no ETB’ is £4355/QALY from the healthcare perspective. From the broader societal perspective, ETB is more effective and cost saving.ConclusionsMonitoring negative emotional bias in primary care in England for personalised antidepressant treatment using ETB seems as an effective and cost-effective option under all considered scenarios (including worst case). Its main economic value seems to lie in reduced productivity loss as opposed to healthcare savings.Clinical implicationsThe test supports accelerated application of evidence-based depression care. Further optimisation and implementation in the ongoing European PReDicT trial is ongoing.

Controversy continues with regard to antidepressants and withdrawal. Recent debates have focused on the prevalence and length of withdrawal, and some continue to state that withdrawal from these compounds constitutes ‘addiction’. In this editorial we examine the evidence underlying these recent debates. We acknowledge gaps in knowledge, and make suggestions for how the field can progress.

BackgroundLithium is the best documented maintenance treatment in bipolar disorder, but its use varies considerably across and within countries. It is not known whether regional differences in lithium prescription rates translate to differing regional outcomes.AimsTo estimate associations between county specific lithium prescription rates and county specific recurrence odds of bipolar disorder in Sweden.MethodData from 14,616 patients with bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified were extracted from the Swedish national quality assurance register for bipolar disorders (BipoläR). Lithium prescription frequencies were calculated for 21 counties. Logistic regression analyses were run adjusted for confounders, with any type of recurrence as primary outcome, and incident elated and depressive episodes as secondary outcomes. Subsets of patients with bipolar I, II and not otherwise specified disorder were also analysed separately.ResultsLithium prescription rates for populations with all bipolar subtypes ranged across counties from 37.7 to 84.9% (mean 52.4%). Higher regional prescription rates were significantly associated with lower rate of any type of recurrence. The association was stronger when bipolar I disorder was analysed separately.ConclusionsThe advantages for lithium use long acknowledged for bipolar I disorder are also seen for the rest of the bipolar spectrum. Results suggest that population level outcomes of bipolar disorder could be improved by increasing the number of patients using lithium.

Background: Remote monitoring and digital phenotyping harbor potential to aid clinical diagnosis, predict episode course and recognize early signs of mental health crises. Digital communication metrics, such as phone call and short message service (SMS) use may represent novel biomarkers of mood and diagnosis in Bipolar Disorder (BD) and Borderline Personality Disorder (BPD).Materials and Methods: BD (n = 17), BPD (n = 17) and Healthy Control (HC, n = 21) participants used a smartphone application which monitored phone calls and SMS messaging, alongside self-reported mood. Linear mixed-effects regression models were used to assess the association between digital communications and mood symptoms, mood state, trait-impulsivity, diagnosis and the interaction effect between mood and diagnosis.Results: Transdiagnostically, self-rated manic symptoms and manic state were positively associated with total and outgoing call frequency and cumulative total, incoming and outgoing call duration. Manic symptoms were also associated with total and outgoing SMS frequency. Transdiagnostic depressive symptoms were associated with increased mean incoming call duration. For the different diagnostic groups, BD was associated with increased total call frequency and BPD with increased total and outgoing SMS frequency and length compared to HC. Depression in BD, but not BPD, was associated with decreased total and outgoing call frequency, mean total and outgoing call duration and total and outgoing SMS frequency. Finally, trait-impulsivity was positively associated with total call frequency, total and outgoing SMS frequency and cumulative total and outgoing SMS length.Conclusion: These results identify a general increase in phone call and SMS communications associated with self-reported manic symptoms and a diagnosis-moderated decrease in communications associated with depression in BD, but not BPD, participants. These findings may inform the development of clinical tools to aid diagnosis and remote symptom monitoring, as well as informing understanding of differential psychopathologies in BD and BPD.

Objective : To examine the evolution of dementia in HIV-positive injecting drug users (IDU) in Edinburgh. Design : Case-control study. Participants : Twenty six (6%) out of 404 patients in the Edinburgh cohort of HIV-positive IDU who have developed HIV-1-associated dementia in the 10 years since infection and seroconversion. Methods : Patients were tested repeatedly, where possible, on a range of neuropsychological and neurophysiological measures. The results from patients with dementia were compared with those of age, sex and IQ-matched non-demented HIV-positive controls from the cohort. An auditory event-related potential (P3 or P300), a neurophysiological measure of cognitive function, detected the onset of a marked slowing of cognitive and psychomotor functions. Neuropsychological measures that involve the speed of information processing such as the Trail-Making task also identified the early stages of dementia. Results : Dementia was associated with a more advanced stage of systemic disease, increased rates of decline in CD4 cell counts and markedly reduced survival compared with the non-demented controls. No evidence for a protective effect of treatment with zidovudine was detected. Conclusion : In the first 10 years after infection with HIV-1 dementia is an individual development, not the clinical extreme of general intellectual impairment, and had occurred in at least 6% of our IDU cohort. Future questions concern the long-term rate of dementia, the critical neuropathological change and the true potential for early treatment.

Background Anxiety is highly prevalent in people diagnosed with bipolar disorder (BD), and can persist between acute episodes of mania and depression. Recent studies indicate that people with BD are prone to experiencing frequent, intrusive and emotional mental images which further fuel their levels of anxiety and mood instability. These intrusive emotional mental images represent a specific target for treatment for this disorder with the potential to reduce anxiety and improve mood stability. A new brief structured psychological intervention for BD called Imagery Based Emotion Regulation (IBER) has been developed, which translates experimental work in the area of imagery and emotion into a skills training programme to improve the regulation of intrusive and distressing emotional mental images in BD. A feasibility trial is required in order to assess whether a full randomised controlled trial is indicated in order to evaluate this approach. Methods The design is a two-arm feasibility randomised controlled trial (RCT), with 1:1 randomisation stratified by trial site and minimised on medication status and anxiety severity. Participants are 60 individuals diagnosed with bipolar disorder and experiencing at least a mild level of anxiety. Sites are defined by the geographical boundaries of two National Health Service (NHS) Trusts, with recruitment from NHS teams, GP surgeries and self-referral. The intervention is up to 12 sessions of Imagery Based Emotion Regulation within 16 weeks. The comparator is NHS standard care. The primary aim is to assess the feasibility of conducting a powered multi-site RCT to evaluate effectiveness. Measures of anxiety, depression, mania, mood stability and health care use will be conducted at baseline, end of treatment and at 16-week follow-up. Discussion This is the first feasibility trial of an imagery-based intervention for the treatment of anxiety in bipolar disorder. If the trial proves feasible, a large multi-site trial will be required. Trial registration ISRCTN16321795. Registered on October 16, 2018. 10.1186/ISRCTN16321795

Bipolar disorder is a chronic neuropsychiatric condition associated with mood instability, where patients present significant sleep and circadian rhythm abnormalities. Currently, the pathophysiology of bipolar disorder remains elusive, but treatment with lithium continues as the benchmark pharmacotherapy, functioning as a potent mood stabilizer in most, but not all patients. Lithium is well documented to induce period lengthening and amplitude enhancement of the circadian clock. Based on this, we sought to investigate whether lithium differentially impacts circadian rhythms in bipolar patient cell lines and crucially if lithium’s effect on the clock is fundamental to its mood-stabilizing effects. We analyzed the circadian rhythms of bipolar patient-derived fibroblasts (n = 39) and their responses to lithium and three further chronomodulators. Here we show, relative to controls (n = 23), patients exhibited a wider distribution of circadian period (p

Antidepressants must be taken for weeks before response can be assessed with many patients not responding to the first medication prescribed. This often results in long delays before effective treatment is started. Antidepressants induce changes in the processing of emotional stimuli early in the course of treatment. In the current study we assessed whether changes in emotional processing and subjective symptoms over the first week of antidepressant treatment predicted clinical response after 4-8 weeks of treatment. Such a predictive test may shorten the time taken to initiate effective treatment in depressed patients. Seventy-four depressed primary care patients completed measures of emotional bias and subjective symptoms before starting antidepressant treatment and then again 1 week later. Response to treatment was assessed after 4-6 weeks. The performance of classifiers based on these measures was assessed using a leave-one-out validation procedure with the best classifier then tested in an independent sample from a second study of 239 patients. The combination of a facial emotion recognition task and subjective symptoms predicted response with 77% accuracy in the training sample and 60% accuracy in the independent study, significantly better than possible using baseline response rates. The face based measure of emotional bias provided good quality data with high acceptability ratings. Changes in emotional processing can provide a sensitive early measure of antidepressant efficacy for individual patients. Early treatment induced changes in emotional processing may be used to guide antidepressant therapy and reduce the time taken for depressed patients to return to good mental health.

Depression and anxiety are negative emotional states familiar to us all through personal experience. Less familiar are severe states of depression, in particular, which can actually shorten the lives of sufferers by over a decade. The relationship of these very severe states of illness to the milder cases more common earlier in development is important. Most patients who have suffered from depression will suffer from further episodes during their lifetime, and an early onset may make recurrence more likely. A number of factors increase the risk for depression, including family history, stressful life events, early life experiences, personality (particularly the traits of neuroticism and perfectionism) and mood lability (marked ups and downs). Sleep disturbance may both provoke and/or signal the onset of mood disorder. Sleep is therefore doubly important as a gateway to treatment. Understanding more about how sleep interacts with the established risk factors would allow vulnerable young people to be identified earlier for more effective intervention. Early identification of sleep disorder and depression allows psychological treatments to be used, which are less effective once a full depressive episode and a cascade of neurobiological and psychological effects have occurred.

Background:Cognitive behavioral therapy (CBT) is an efficacious intervention for generalized anxiety disorder (GAD). Digital CBT may provide a scalable means of delivering CBT at a population level. We investigated the efficacy of a novel digital CBT program in those with GAD for outcomes of anxiety, worry, depressive symptoms, sleep difficulty, wellbeing, and participant‐specific quality of life. Methods:This online, two‐arm parallel‐group superiority randomized controlled trial compared digital CBT with waitlist control in 256 participants with moderate‐to‐severe symptoms of GAD. Digital CBT (Daylight), was delivered using participants’ own smartphones. Online assessments took place at baseline (Week 0; immediately preceding randomization), mid‐intervention (Week 3; from randomization), post‐intervention (Week 6; primary endpoint), and follow‐up (Week 10). Results:Overall, 256 participants were randomized and intention‐to‐treat analysis foundDaylightreduced symptoms of anxiety compared with waitlist control at post‐intervention, reflecting a large effect size (adjusted difference [95% CI]: 3.22 [2.14, 4.31],d = 1.08). Significant improvements were found for measures of worry; depressive symptoms, sleep difficulty, wellbeing, and participant‐specific quality of life. Conclusion:Digital CBT (Daylight) appears to be safe and efficacious for symptoms of anxiety, worry, and further measures of mental health compared with waitlist control in individuals with GAD.

This chapter was edited from Professor Pichot’s contribution to the last edition. It presents a history of psychiatry from the perspective of doctors. It is not a historigraphy of mental illness, that is a history of how it has been described or written about by other groups or individuals. Nor is it a history of the people who have suffered with mental illness over the centuries. It describes the evolution of what is sometimes called the medical model of severe mental illness, starting with the founders of humane care, such as Pinel, and moving to the idea of an objective psychopathology, the confounding by psychological explanation, and the continuing conflicts between those favouring biological opposed to social approaches to aetiology and treatment.

BACKGROUND People with intellectual disabilities (IDs) have very high rates of osteoporosis and fractures, to which their widespread vitamin D deficiency and other factors could contribute. We aimed to assess in people with IDs previously treated for vitamin D deficiency (1) long-term adherence to vitamin D supplementation and (2) bone mineral density (BMD), as an indicator for risk of fractures, according to vitamin D supplementation and other factors. METHOD We recorded height, weight, medical, pharmacological, dietary and lifestyle assessment. Blood sample were taken for vitamin D and related analytes. dual-energy X-ray absorptiometry for BMD was performed. RESULTS Of 51 study participants (mean [standard deviation, SD] age 51.5 [13.6] years, 57% male), 41 (80.4%) were taking vitamin D and 10 were not. Mean [SD] serum vitamin D was 81.3 [21.3] vs. 25.2 [10.2] nmol/L (P

Objectives: For the first time to present a systematic review of observational studies on the efficiency of lithium monotherapy in comparison with other maintenance mood stabilizers and in combination. Methods: As part of the International Society for Bipolar Disorders (ISBD) Task Force on Lithium Treatment we undertook a systematic literature search of non-randomized controlled observational studies on 1) lithium monotherapy versus treatment with another maintenance mood stabilizer in monotherapy 2) lithium in combination with other mood stabilizers versus monotherapy. Results: In eight out of nine identified studies including more than a total of 14.000 patients, maintenance lithium monotherapy was associated with improved outcome compared with another mood stabilizer in monotherapy including valproate, lamotrigine, olanzapine, quetiapine, unspecified anticonvulsants, carbamazepine/lamotrigine, unspecified atypical antipsychotics and unspecified antipsychotics. Among the four identified studies including a total of more than 4.000 patients comparing maintenance combination therapy with maintenance monotherapy, a few combination therapies were found to be superior to monotherapy in some analyses, but many were not. Conclusions: The results show the superiority in real life of lithium monotherapy compared with monotherapy with other maintenance mood stabilizers. The four largest register-based studies largely addressed confounding, but, as ever, residual confounding cannot be excluded. Nevertheless, the observational findings substantially add to the findings from randomized controlled trials, whose designs often limit the validity of comparison between medicines.

Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients. Trial registration ClinicalTrials.gov, ID: NCT02790970. Registered on 30 March 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2247-2) contains supplementary material, which is available to authorized users.

Contains fulltext : 191289.pdf (Publisher’s version ) (Open Access) Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 x 10(-21)), left fusiform gyrus (d=-0.288; P=8.25 x 10(-21)) and left rostral middle frontal cortex (d=-0.276; P=2.99 x 10(-19)). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

BackgroundClinical trials have examined the efficacy of drugs to prevent relapse in patients with bipolar disorder, however, their design often limits generalisation to routine clinical practice.AimsTo estimate the effectiveness of drugs used for maintenance treatment in bipolar disorder.MethodWe used national registers to identify 35022 individuals diagnosed with bipolar disorder and information on lithium, valproate, carbamazepine, lamotrigine, quetiapine and olanzapine treatment from 2006 to 2009. The main outcome was psychiatric hospital admissions. We used stratified cox regression to compare periods on and off medication within the same individual.ResultsMedication with lithium, valproate, lamotrigine, olanzapine and quetiapine was associated with reduced rates of admission to hospital. Lithium was more effective than quetiapine and olanzapine. The effects of specific drugs depended on the polarity of the mood episode.ConclusionsOur findings complement results from randomised controlled trails, but suggest that lithium is more effective than both quetiapine and olanzapine in routine clinical practice.

Introduction: Lockdowns implemented in response to the COVID-19 pandemic are thought to impact mental health [1,2] Understanding the mechanisms underlying this impact is critical to mitigating it [3] We tested the hypothesis that one such mechanism involves impaired mood homeostasis (i e , failure to stabilize mood via mood-modifying activities) [4,5] Methods: In this ecological momentary assessment cohort study, students in the Netherlands reported their mood and activities 4 times a day between March 16 and 29, 2020 New and immediate lockdown measures were announced on March 23 The average change in mood an individual experienced when engaging in an activity was recorded as its pleasantness Mood homeostasis was defined as the extent to which participants preferentially engaged in pleasant activities at time t+1 when their mood was low at time t, thus stabilizing their mood Participants' history of mental illness was screened at baseline Using linear regressions we assessed (i) changes in mood homeostasis from before to during lockdown, (ii) their moderation by mental illness history, (iii) their association with changes in mood level, and (iv) their mediation by changes in range of activities undertaken How changes in mood homeostasis might impact the risk of depression was estimated using computer simulations Statistical significance was set at 2-sided P< 05 Results: Seventy-eight students were included Mood homeostasis was significantly higher before than during lockdown (0 37 vs 0 28;95% CI of the difference [0 03,0 15];P= 003) For every 0 1 point drop in mood homeostasis, average mood decreased by 1 9 points (95% CI, [1 3,3 6], P< 001) This is enough to bring someone's average mood from the population's mean to its bottom quartile The change in mood homeostasis from before to during lockdown was mediated by a reduction in the range of activities (proportion mediated: 11 9%, P< 001) Mood homeostasis dropped significantly more among people with (vs without) a history of mental illness (P< 001): from similar values before lockdown (0 31 vs 0 36;P= 37) to significantly different values during lockdown (0 13 vs 0 35;95% CI of the difference [0 11,0 33];P< 001) In computer simulations, changes in mood homeostasis attributed to the lockdown led to a 3-fold increase in the the yearly incidence of depressed mood episodes: from 9 0% (95% CI [6 6%,11 4%]) before lockdown to 28 2% (95% CI [23 6%,32 6%]) during lockdown Conclusions: Mood homeostasis appears to decrease during lockdown Larger decreases correlate with larger decreases in mood level The impact was larger for students with a history of mental illness The lack of a control group (as the lockdown was implemented nationally) is the main limitation of our study However, since the same participants were monitored before and during lockdown, the lockdown itself seems to be the most likely explanation for the observed difference Identifying interventions that increase mood homeostasis might be a promising avenue to mitigate the impact of lockdowns on mental health Table 1 No conflict of interest

Background: The limited reliability of depression diagnosis impedes research in psychiatry. This impediment is often attributed to biases in the reporting and recording of symptoms. But a fundamental and overlooked explanation may lie in the ambiguity of the very definition of depressed mood. Digital phenotyping enables isolating the effects of this ambiguity from other factors. Methods: We used data from two large independent ecological momentary assessment studies: the 58sec study for testing and the Emotion Sense study for replication. We compared the yearly incidences of depressed mood episodes from 125 interpretations of the ICD-10 criteria. We then assessed agreement between interpretations that lead to similar (and realistic) yearly incidences. Outcomes: In the 58sec and Emotion Sense studies, respectively 2042 and 2009 people reported their mood frequently for an average of 114 and 132 days. Vastly different yearly incidences of depressed mood episodes were observed for different interpretations of the ICD-10 criteria (0%–65.7% in the 58sec study, and 0.3%–52.8% in the Emotion Sense study). Interpretations leading to similar yearly incidence identified different depressive episodes (Cohen’s kappa as low as 0.25 in the 58sec study and 0.47 in the Emotion Sense study). Interpretation: A fundamental cause for the unreliability of depression diagnosis appears to lie in the ambiguity of the definition of depressed mood. Improving this definition with digital phenotyping can be achieved if measurements are combined with a representation of depressed mood along underlying dimensions. Our findings thus offer a potential bridge between conventional diagnostic practice and newer dimensional approaches to psychopathology. Funding Statement: National Institute of Health Research. Declaration of Interests: Prof Goodwin is Medical Director at P1vital products, holds shares in P1vital and P1Vital products and has served as consultant, advisor or CME speaker in the last 3 years for Beckley Psytech, Clerkenwell Health, Compass pathways, Evapharma, Janssen, Lundbeck, Medscape, Novartis, P1Vital, Sage, Servier. The other authors declare no conflict of interest. Ethics Approval Statement: The 58sec study was approved by the Ethics Committee of ESADE (Escuela Superior de Administracion y Direccion de Empresas) Business School, Barcelona, Spain. The Emotion Sense study was approved by the Research Ethics Committee of the University of Cambridge.

Background and objectives Cognitive behavioral therapy (CBT) is a first-line treatment for anxiety, but it is not widely available as clinical guidelines recommend. We examined the feasibility and efficacy of a novel smartphone-based fully automated digital CBT intervention, ‘Daylight™‘, to improve symptoms of Generalized Anxiety Disorder (GAD). Methods In this multiple-baseline design, 21 adults (20 F; mean age 43yrs. range 19–65yrs.) with moderate-to-severe symptoms of GAD were randomized to one of three baseline durations (2-, 4-, or 6-weeks) and then received access to digital CBT. Participants completed daily ratings of anxiety and worry, weekly measures of anxiety, depressive symptoms, and sleep, and measures of anxiety, worry, wellbeing, quality of life, CBT skill acquisition, and work performance at initial assessment prior to baseline randomization, post-intervention, and follow-up. Results Digital CBT was found to be feasible in terms of engagement, satisfaction, and safety. For preliminary efficacy, improvements were detected in daily and weekly outcomes of anxiety for most participants. Despite individual differences, significant improvements occurred with the introduction of digital CBT and not during baseline. Overall, 70% of participants no longer had clinically significant symptoms of GAD, 61% no longer had significant depressive symptoms, and 40% no longer had significant sleep difficulty at post-intervention. Limitations The study sample was recruited using the internet and was mostly female, limiting the generalizability of the findings. Conclusions Findings support the feasibility and efficacy of Daylight. Further examination in randomized controlled trials is now warranted.

BackgroundThere is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder.AimsWe conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder.MethodWe used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses.ResultsAcross different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10−8, lifetime smoking ORIVW = 1.72, 95% CI 1.29–2.28, P = 1.8 × 10−4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003–0.053, P = 2.9 × 10−2).ConclusionsThese findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.

Study objectives Intrusive memories of psychological trauma are a core clinical feature of posttraumatic stress disorder (PTSD), and in the early period post-trauma may be a potential target for early intervention. Disrupted sleep in the weeks post-trauma is associated with later PTSD. The impact of sleep and intrusive memories immediately post-trauma, and their relation to later PTSD, is unknown. This study assessed the relationship between sleep duration on the first night following a real-life traumatic event and intrusive memories in the subsequent week, and how these might relate to PTSD symptoms at 2 months. Methods Patients (n = 87) recruited in the emergency department completed a sleep and intrusive memory diary from the day of their trauma and for the subsequent week, with optional actigraphy. PTSD, anxiety, and depression symptoms were assessed at 1 week and 2 months. Results A U-shaped relationship was observed between sleep duration on the first night and intrusive memories over the subsequent week: sleeping “too little” or “too much” was associated with more intrusive memories. Individuals who met Clinician-Administered PTSD Scale (CAPS) criteria for PTSD at 2 months had three times more intrusive memories in the first week immediately post-trauma than those who did not (M = 28.20 vs 9.96). Post hoc analysis showed that the absence of intrusive memories in the first week post-trauma was only observed in those who did not meet CAPS criteria for PTSD at 2 months. Conclusions Monitoring intrusive memories and sleep in the first week post-trauma, using a simple diary, may help identify individuals more vulnerable to later psychopathology.

Objectives: Emotional processing abnormalities have been implicated in bipolar disorder (BD) but studies are typically small and uncontrolled. Here, facial expression recognition was explored in a large and naturalistically recruited cohort of BD patients. Methods: 271 patients with BD completed the facial expression recognition task. The effects of current medication together with the influence of current mood state and diagnostic subtype were assessed whilst controlling for the effects of demographic variables. Results: Patients who were currently receiving treatment with lithium demonstrated significantly poorer accuracy in recognising angry faces, an effect that held in a monotherapy sub-analysis comparing those participants on lithium only and those who were medication-free. Accuracy in recognising angry faces was also lower amongst participants currently taking dopamine antagonists (antipsychotics). Higher levels of current depressive symptoms were linked to poorer accuracy at identifying happy faces. Conclusion: Use of lithium and possibly dopamine antagonists may be associated with reduced processing of anger cues in BD. Findings support the existence of mood-congruent negative biases associated with depressive symptoms in BD. Observational cohort studies provide opportunities to explore the substantial effects of demographic, psychometric and clinical variables on cognitive performance and emotional processing.

In 1997, neuropsychological and neuroimaging evidence supported the involvement of the frontal lobes and indeed the brain in depression. This was a challenge to conventional phenomenology and linked with the imperative to use neuroscience to understand major mental illness. Since that time, we are seeing ever more convincing evidence for the genetic basis of mental illness (including depression), relevant abnormality in grey and white matter and neuropsychological analysis of brain function. It has proved more difficult to pin down structural abnormality in major depression at the cellular level, but a focus on glial cells is increasingly justified by the evidence. Neuroscience continues to be a buttress against anti-scientific impulses in psychiatry and can help attract young people to enter it as a profession.

There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder. We aimed to investigate the direction and causal nature of the relationship between smoking and bipolar disorder we conducted a bidirectional Mendelian randomization (MR) study. Publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e., a compound measure of heaviness, duration and cessation). We applied multiple analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger or Egger SIMEX, weighted median, weighted mode, and Steiger filtered analyses. Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW=1.46, 95% CI=1.28-1.66, P=1.44x10-8, lifetime smoking ORIVW=1.72, 95% CI=1.29-2.28, P=1.8x10-4). The MR analyses of the liability of bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW=0.028, 95% CI= 0.003-0.053, P=2.9x10-2). These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.

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Background Faecal calprotectin [FCal] levels are used as a surrogate marker for mucosal inflammation, but thresholds for defining endoscopic or histological disease activity in ulcerative colitis [UC] remain unclear. Methods Using validated indices, prospective measurements of FCal, symptoms [Simple Colitis Clinical Activity Index, SCCAI], endoscopic [Ulcerative Colitis Endoscopic Index of Severity, UCEIS] and histological activity [Nancy index] were made over 6 months in patients enrolled into the TrueColours UC web-based monitoring programme. Repeated measurements correlation was performed between FCal and SCCAI, UCEIS, and Nancy indices using definitions for remission and active disease [UCEIS: remission ≤1, active ≥4; Nancy: remission ≤1, active ≥2; combined criteria: remission UCEIS ≤1 and Nancy ≤1, active UCEIS ≥4 and Nancy ≥2]. Receiver operating characteristic curves investigated FCal thresholds after maximising sensitivity for active disease. Results In 39 patients followed prospectively for 6 months, correlation coefficients between FCal and SCCAI, UCEIS, and Nancy indices were 0.271 (95% confidence interval [CI] 0.114–0.415), 0.741 [95% CI 0.289–0.922], and 0.876 [95% CI 0.605–0.965], respectively. Median FCal thresholds for remission using endoscopic, histological, or combined criteria were 71 μg/g [range 8–624], 91 μg/g [range 8–858], and 67 μg/g [range 8–479], respectively. The FCal threshold above which active disease was confirmed was 187 μg/g for UCEIS (area under the curve [AUC] 0.915), 72 μg/g for Nancy [AUC 0.824], and 187 μg/g for combined endoscopic and histological criteria [AUC 0.936]. Conclusions Correlation between FCal and symptoms in UC is weak. In contrast, the correlation between FCal and endoscopic or histological activity is strong. An FCal ≥72 μg/g indicates histological inflammation [Nancy ≥2] and ≥187 μg/g indicates endoscopically active disease [UCEIS ≥4], whether combined with histopathology or not.

Objectives Although not licensed for acute bipolar depression, lamotrigine has evidence for efficacy in trials and its use is recommended in guidelines. So far there had been no prospective health economic evaluation of its use. Methods Cost‐utility analysis of the CEQUEL trial comparing quetiapine plus lamotrigine vs quetiapine monotherapy (and folic acid vs placebo in an add‐on factorial design) for patients with bipolar depression (n = 201) from the health and social care perspective. Differences in costs together with quality‐adjusted life years (QALYs) between the groups were assessed over 52 weeks using a regression‐based approach. Results Health‐related quality of life improved substantially for all randomization groups during follow‐up with no significant difference in QALYs between any of the comparisons (mean adjusted QALY difference: lamotrigine vs placebo −0.001 (95% CI: −0.05 to 0.05), folic acid vs placebo 0.002 (95% CI: −0.05 to 0.05)). While medication costs in the lamotrigine group were higher than in the placebo group (£647, P

Background:Despite the global impact of bipolar disorder (BD), treatment success is limited. Challenges include syndromal and subsyndromal mood instability, comorbid anxiety, and uncertainty around mechanisms to target. The Oxford Mood Action Psychology Programme (OxMAPP) offered a novel approach within a cognitive behavioural framework, via mental imagery-focused cognitive therapy (ImCT).Aims:This clinical audit evaluated referral rates, clinical outcomes and patient satisfaction with the OxMAPP service.Method:Eleven outpatients with BD received ImCT in addition to standard psychiatric care. Mood data were collected weekly from 6 months pre-treatment to 6 months post-treatment via routine mood monitoring. Anxiety was measured weekly from start of treatment until 1 month post-treatment. Patient feedback was provided via questionnaire.Results:Referral and treatment uptake rates indicated acceptability to referrers and patients. From pre- to post-treatment, there was (i) a significant reduction in the duration of depressive episode relapses, and (ii) a non-significant trend towards a reduction in the number of episodes, with small to medium effect size. There was a large effect size for the reduction in weekly anxiety symptoms from assessment to 1 month follow-up. Patient feedback indicated high levels of satisfaction with ImCT, and underscored the importance of the mental imagery focus.Conclusions:This clinical audit provides preliminary evidence that ImCT can help improve depressive and anxiety symptoms in BD as part of integrated clinical care, with high patient satisfaction and acceptability. Formal assessment designs are needed to further test the feasibility and efficacy of the new ImCT treatment on anxiety and mood instability.

BackgroundAdjunctive antidepressant therapy is commonly used to treat acute bipolar depression but few studies have examined this strategy.AimsTo examine the efficacy of agomelatine v. placebo as adjuncts to lithium or valproate in bipolar depression.MethodPatients who were currently depressed despite taking lithium or valproate for at least 6 weeks were randomised to treatment with agomelatine (n = 172) or placebo (n = 172) for 8 weeks of acute therapy and 44 weeks of continuation therapy (trial registration: ISRCTN28588282).ResultsNo significant differences in improvement of depressive symptoms were observed between the two groups either at 8 weeks or 52 weeks on the primary efficacy measure of change in Montgomery–Åsberg Depression Rating Scale scores from baseline to end-point. Adverse events including switches into mania/hypomania were low and similar in both groups.ConclusionsAgomelatine adjunctive therapy was not superior to placebo adjunctive therapy for acute bipolar depression.

The anxiety disorders include generalized anxiety disorder, specific phobia, social phobia, agoraphobia, and panic disorder. In addition to the specific symptoms of these disorders, there may be a common experience of anxiety and even dysphoria across the conditions, and of course recourse to the same drug or choice of drugs for treatment. This overlap probably occurs because of universal dimensions of distress or negative affectivity, a shared genetic predisposition, and a common neurobiology Evidence of shared genes is still based mainly on twin studies, but the shared neurobiology can be investigated directly by the investigation of emotional or cognitive bias either behaviorally or using functional brain imaging. This intermediate phenotype can then provide a substrate for understanding and developing medicines and psychological treatments.Los trastornos de ansiedad incluyen el trastorno de ansiedad generalizada, la fobia específica, la fobia social, la agorafobia y el trastorno de pánico. Además de los síntomas específicos de estos trastornos, en estas condiciones puede existir una experiencia común de ansiedad e incluso disforia y, por supuesto, el hecho de recurrir al mismo fármaco o a la elección de medicamentos para el tratamiento. Esta sobreposición se debe probablemente a las dimensiones universales del distrés o afectividad negativa, a una predisposición genética compartida y a una neurobiología común. Todavía la evidencia de genes compartidos se basa principalmente en estudios en gemelos, pero la neurobiología compartida puede ser investigada directamente por medio de la investigación de sesgos emocionales o cognitivos ya sea a través del comportamiento o empleando imágenes cerebrales funcionales. Este fenotipo intermedio puede proporcionar entonces un sustrato para la comprensión y el desarrollo de medicamentos y terapias psicológicas.L'anxiété généralisée, la phobie spécifique, la phobie sociale, l'agoraphobie et le trouble panique font partie des troubles anxieux. En plus des symptômes propres à ces troubles, il peut cependant exister un vécu commun d'anxiété et même de dysphorie entre ces pathologies, nécessitant bien sûr un recours au même médicament ou au même choix de médicament pour le traitement. Les dimensions universelles de la souffrance ou de l'affectivité négative, une prédisposition génétique partagée et une neurobiologie commune sont probablement à l'origine de ce chevauchement. Les données des gènes partagés sont toujours fondées sur des études de jumeaux, mais la neurobiologie partagée peut être étudiée directement par la recherche de biais émotionnels ou cognitifs soit de façon comportementale ou en utilisant l'imagerie cérébrale fonctionnelle. Ce phénotype intermédiaire peut alors fournir un substrat pour comprendre et développer des médicaments et des traitements psychologiques.

International audience; Bipolar disorder is associated with impaired decision-making. Little is known about how treatment, especially lithium, influences decision-making abilities in bipolar patients when euthymic. We aimed at testing for an association between lithium medication and decision-making performance in remitted bipolar patients. Decision-making was measured using the Iowa Gambling Task in 3 groups of subjects: 34 and 56 euthymic outpatients with bipolar disorder, treated with lithium (monotherapy and lithium combined with anticonvulsant or antipsychotic) and without lithium (anticonvulsant, antipsychotic and combination treatment), respectively, and 152 matched healthy controls. Performance was compared between the 3 groups. In the 90 euthymic patients, the relationship between different sociodemographic and clinical variables and decision-making was assessed by stepwise multivariate regression analysis. Euthymic patients with lithium (p=0.007) and healthy controls (p=0.001) selected significantly more cards from the safe decks than euthymic patients without lithium, with no significant difference between euthymic patients with lithium and healthy controls (p=0.9). In the 90 euthymic patients, the stepwise linear multivariate regression revealed that decision-making was significantly predicted (p

Pharmacotherapy is effective in helping many patients suffering from psychiatric and neurological disorders, and both psychotherapeutic and stimulation-based techniques likewise have important roles to play in their treatment. However, therapeutic progress has recently been slow. Future success for improving the control and prevention of brain disorders will depend upon deeper insights into their causes and pathophysiological substrates. It will also necessitate new and more rigorous methods for identifying, validating, developing and clinically deploying new treatments. A field of Research and Development (R and D) that remains critical to this endeavour is Neuropsychopharmacology which transformed the lives of patients by introducing pharmacological treatments for psychiatric disorder some 60 years ago. For about half of this time, the European College of Neuropsychopharmacology (ECNP) has fostered efforts to enhance our understanding of the brain, and to improve the management of psychiatric disorders. Further, together with partners in academia and industry, and in discussions with regulators and patients, the ECNP is implicated in new initiatives to achieve this goal. This is then an opportune moment to survey the field, to analyse what we have learned from the achievements and failures of the past, and to identify major challenges for the future. It is also important to highlight strategies that are being put in place in the quest for more effective treatment of brain disorders: from experimental research and drug discovery to clinical development and collaborative ventures for reinforcing "R and D". The present article sets the scene, then introduces and interlinks the eight articles that comprise this Special Volume of European Neuropsychopharmacology. A broad-based suite of themes is covered embracing: the past, present and future of "R and D" for psychiatric disorders; complementary contributions of genetics and epigenetics; efforts to improve the treatment of depression, neurodevelopmental and neurodegenerative disorders; and advances in the analysis and neuroimaging of cellular and cerebral circuits.

Background Online self-monitoring of mood can be used to investigate differences in course patterns across patient groups. This study explored the feasibility of remote symptom capture with True Colours, a self-rated online mood monitoring tool completed on a weekly basis. Methods Participants with bipolar disorder (N = 297) completed weekly depression and mania questionnaires over an average of 27.5 months (range 1 –81 months). Subgroups defined by sex, age, and bipolar I vs. II status were compared on time in various mood states, number of episodes, and week-to-week mood variability. Results Compliance with weekly questionnaires was generally high (median, 92% of weeks). Mood symptoms occurred for an average of 55.4% of weeks across the follow-up period. Females spent more time with hypomanic/manic and depressive symptoms and had more depressive episodes compared to males. Younger participants were found to experience more hypomanic/manic episodes and showed greater variability in mood symptoms than older participants. No significant differences in mood symptoms or variability were observed between bipolar I and II patients. Limnitations This was a naturalistic study with a heterogeneous cohort, and did not include a control group. True Colours does not identify mood fluctuations that may occur in the days between weekly assessments. Conclusions Monitoring moods through an online tool is both feasible and informative regarding course of illness in patients with bipolar disorder. Interventions aiming to reduce mood variability and manic/hypomanic episodes in the early phases of bipolar disorder may enhance the long-term symptomatic course of the illness.

Background:Remote monitoring of mood disorders may be an effective and low resource option for patient follow-up, but relevant evidence remains very limited. This study explores real-life compliance and health services impacts of mood monitoring among patients with bipolar disorder in the UK.Methods:Patients with a diagnosis of bipolar disorder who were registered users of the True Colours monitoring system for at least 12 months at study assessment were included in this retrospective cohort study (n = 79). Compliance was measured as the proportion of valid depression and mania scale messages received in comparison to their expected numbers over the first 12 months of monitoring. Mental health service use data were extracted from case notes, costed using national unit costs, and compared 12 months before (pre-TC period) and 12 months after (TC period) patients’ engagement with monitoring. Associations with relevant patient factors were investigated in a multiple regression model.Results:Average compliance with monitoring was 82%. Significant increases in the annual use and costs of psychiatrist contacts and total mental health services were shown for patients newly referred to the clinic during the pre-TC period but not for long-term patients of the clinic. Psychiatric medication costs increased significantly between the pre-TC and TC periods (£ 235, P = 0.005) unrelated to patients’ referral status.Conclusions:Remote mood monitoring has good compliance among consenting patients with bipolar disorder. We found no associations between observed changes in mental health service costs and the introduction of monitoring except for the increase in psychiatric medication costs.

Plant-based psychedelics such as psilocybin have an ancient history of medicinal use. After the first English-language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aides to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programmes. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and 3 separate clinical trials of psilocybin for depressive symptoms. In this Circumspective piece, Robin Carhart-Harris and Guy Goodwin share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.

BACKGROUND: Peer support is an established component of recovery from bipolar disorder, and online support groups may offer opportunities to expand the use of peer support at the patient's convenience. Prior research in bipolar disorder has reported value from online support groups.AIMS: To understand the use of online support groups by patients with bipolar disorder as part of a larger project about information seeking.METHODS: The results are based on a one-time, paper-based anonymous survey about information seeking by patients with bipolar disorder, which was translated into 12 languages. The survey was completed between March 2014 and January 2016 and included questions on the use of online support groups. All patients were diagnosed by a psychiatrist. Analysis included descriptive statistics and general estimating equations to account for correlated data.RESULTS AND CONCLUSIONS: The survey was completed by 1222 patients in 17 countries. The patients used the Internet at a percentage similar to the general public. Of the Internet users who looked online for information about bipolar disorder, only 21.0% read or participated in support groups, chats, or forums for bipolar disorder (12.8% of the total sample). Given the benefits reported in prior research, clarification of the role of online support groups in bipolar disorder is needed. With only a minority of patients using online support groups, there are analytical challenges for future studies.

The present paper reports in parallel the findings of the two phase III trials that evaluated the efficacy of agomelatine in older depressed patients. It describes how the particular methodological innovations (particularly in relation to patient selection, design and accuracy of diagnosis of depression) introduced in study 2 have improved the quality of recruitment of patients and the assay sensitivity. Study 1 lacked assay sensitivity, and among the many differences with study 2, the inclusion of unexpected mildly ill patients could have inflated the placebo response. The increased demands on investigators in study 2 appear to have reduced the placebo effect and showed a robust benefit of agomelatine. The two agomelatine studies offer the opportunity to discuss hypotheses that have been raised to explain the low level of response of older patients to available antidepressants.

Emotional blunting is regularly reported in depressed patients on antidepressant treatment but its actual frequency is poorly understood. We have previously used qualitative methods to develop an appropriate scale, the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants (OQESA).Six hundred and sixty nine depressed patients on treatment and 150 recovered (formerly depressed) controls (aged ≥18 years) participated in this internet-based survey. The rate of emotional blunting in treated depressed patients was 46%, slightly more frequent in men than women (52% versus 44%) and in those with higher Hospital Anxiety and Depression (HAD) scale scores. There was no difference according to antidepressant agent, though it appeared less frequent with bupropion. Depressed patients with emotional blunting had much higher total blunting scores on OQESA than controls (42.83 ± 14.73 versus 25.73 ± 15.00, p < 0.0001) and there was a correlation between total blunting score and HAD-Depression score (r = 0.521). Thus, those with HAD-D score >7 (n = 170) had a higher total questionnaire score, 49.23±12.03, than those with HAD-D score ≤7 (n = 140), 35.07 ± 13.98, and the difference between the two groups was highly significant. However, patients with HAD-D score ≤7 (n = 140) had a higher total score (35.07 ± 13.98) than the recovered controls (n = 150) (25.73 ± 15.00), and the difference between the two groups was significant. Among the patients with emotional blunting, 37% had a negative perception of their condition and 38% positive. Men reported a more negative perception than women (p=0.008), and patients with a negative perception were more likely to have higher HAD scores. Higher levels of emotional blunting are associated with a more negative perception of it by the patient (r = -0.423).Include self-evaluation and the modest size of the sample for detection of differences between antidepressants.Emotional blunting is reported by nearly half of depressed patients on antidepressants. It appears to be common to all monoaminergic antidepressants. The OQESA scores are highly correlated with HAD depression score; emotional blunting cannot be described simply as a side-effect of antidepressants, but also as a symptom of depression. A higher degree of emotional blunting is associated with a poorer quality of remission. The OQESA scale allows the detection of this phenomenon.

The publisher regrets the omission of the following Acknowledgements, Role of funding source and Conflict of interest information in the original publication. RHMW, KB, GMG, JH, CK, JR, SS and AHY contributed as authors on the manuscript and meet the criteria for authorship as recommended by the International Committee of Medical Journal Editors. They take full responsibility for the scope, direction, content of, and editorial decisions relating to the manuscript, were involved at all stages of manuscript development and have approved the submitted manuscript. The steering committee was initiated and supported by the pharmaceutical company Lundbeck Ltd, through an educational grant. Lundbeck Ltd had no input or influence on content, on the decision to publish, or on the preparation of the manuscript. Medical writing assistance was contracted and compensated by Lundbeck Ltd. The authors received no compensation related to the development of the manuscript. Conflict of interest disclosures. AHY has received payment for lectures and advisory boards from all major pharmaceutical companies with drugs used in affective and related disorders; is the Lead Investigator for the Embolden Study (AstraZeneca), BCI Neuroplasticity Study and Aripiprazole Mania Study; investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth; and received grant funding (past and present) from NIMH (USA), CIHR (Canada), NARSAD (USA), Stanley Medical Research Institute (USA), MRC (UK), Wellcome Trust (UK), Royal College of Physicians (Edinburgh, UK), BMA (UK), UBC-VGH Foundation (Canada), WEDC (Canada), CCS Depression Research Fund (Canada), MSFHR (Canada) and NIHR (UK). AHY is funded by the NIHR: the views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. GMG has received payment for consulting/advisory roles from H. Lundbeck, Medscape, MSD, Otsuka, Servier, Sunovion and Takeda; received speaker honoraria from H. Lundbeck, Medscape and Servier; received payment for clinical trials/research grants from Bailey Thomas Charitable Trust, Wellcome Trust and NIHR; has stocks with P1VITAL; and received book royalties from Fast Facts: Bipolar Disorder. GMG is an NIHR senior investigator; the views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. JH has in the past 2 years received paid consultancy from the following companies and organisations: Abbvie, Access to Quality, Amgen, Anavex, AstraZeneca, Avonex, Avraham, Axon, Axovant, Biogen Idec, Boehringer Ingelheim, Bracket, Catenion, CRF Health, DeNDRoN, EnVivo Pharma, Enzymotec, ePharmaSolutions, Eisai, Eli Lilly, Forum Pharma, GfHEu, Heptares, Janssen AI, Johnson & Johnson, Kaasa Health, Kyowa Hakko Kirin, Lundbeck, MedAvante, Merck, MyCognition, Mind Agilis, Neurocog, Neurim, Neurotrack, Novartis, Nutricia, Orion Pharma, Pharmanet/i3, Pfizer, Prana Biotech, PriceSpective, Probiodrug, Prophase, Prostrakan, Regeneron, Reviva, Roche, Sanofi, Servier, Shire, Takeda, TCG, TransTech Pharma, Velacor; has received payment for CME activities from Medscape and Lundbeck; holds options and a patent in Neurotrack and MyCognition, respectively; has received royalties from Oxford University Press and Blackwell Publishers; and has received research funding from Memorabel. CK has received honoraria, grant funding and consultancy payments from pharmaceutical companies including H. Lundbeck and Eli Lilly. RHMW has received speaker fees from AstraZeneca, Bristol Myers-Squibb, Eli Lilly, Ferrer, GlaxoSmithKline, Janssen-Cilag, H. Lundbeck, Merck Sharp & Dohme, Pfizer, Servier, SPIMACO, Sunovian and Wyeth; received consultancy fees from AstraZeneca, Bristol Myers-Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, H. Lundbeck, Merck Sharp & Dohme, MyTomorrow, Servier, Sunovian and Wyeth; and received independent investigator-led research support from AstraZeneca, Eli Lilly and Wyeth. JR has received payment for consultancy/advisory boards/Speaker Bureaus from Alzheimer's Society, Cerestim Ltd, Chase Pharmaceuticals, Edmund de Rothschild, Eli Lilly, H. Lundbeck, Ono, Otsuka, Pfizer, Roche, Servier, Wellcome Trust and Psi-napse, and is a non-executive Director for Cerestim. KB and SS have no conflicts of interest to disclose.

The True Colours remote mood monitoring system was developed over a decade ago by researchers, psychiatrists, and software engineers at the University of Oxford to allow patients to report on a range of symptoms via text messages, Web interfaces, or mobile phone apps. The system has evolved to encompass a wide range of measures, including psychiatric symptoms, quality of life, and medication. Patients are prompted to provide data according to an agreed personal schedule: weekly, daily, or at specific times during the day. The system has been applied across a number of different populations, for the reporting of mood, anxiety, substance use, eating and personality disorders, psychosis, self-harm, and inflammatory bowel disease, and it has shown good compliance. Over the past decade, there have been over 36,000 registered True Colours patients and participants in the United Kingdom, with more than 20 deployments of the system supporting clinical service and research delivery. The system has been adopted for routine clinical care in mental health services, supporting more than 3000 adult patients in secondary care, and 27,263 adolescent patients are currently registered within Oxfordshire and Buckinghamshire. The system has also proven to be an invaluable scientific resource as a platform for research into mood instability and as an electronic outcome measure in randomized controlled trials. This paper aimed to report on the existing applications of the system, setting out lessons learned, and to discuss the implications for tailored symptom monitoring, as well as the barriers to implementation at a larger scale.

Objectives Polyuria increases the risk of dehydration and lithium toxicity in lithium-treated patients. Risk factors have been inconsistently described and the variance of this adverse effect remains poorly understood. This study aimed to establish independent risk factors for polyuria in a community, secondary-level lithium-treated sample of patients. Methods This was a cross-sectional study of the lithium-treated patients attending a general adult and an old age psychiatry service. Participants completed a 24-hour urine collection. Urine volume and the presence of polyuria were the outcomes of interest. The relationship between outcome and the participant's demographic and clinical characteristics was explored with univariable and multivariable analysis. Results A total of 122 participants were included in the analysis, with 38% being diagnosed with polyuria. Female gender and increased body weight independently predicted the presence of polyuria (standardized regression coefficient 1.01 and 0.94, respectively; p = 0.002 and p = 0.003, respectively). Female gender and increased body weight, lithium dose, and duration of lithium treatment independently predicted higher 24-hour urine volumes (standardized regression coefficients 0.693, p

Background: Synergistic effects of NK1 receptor antagonism combined with serotonin reuptake inhibition have been reported in preclinical models. GSK424887 is a selective competitive antagonist of the human NK1 receptor and inhibitor of the serotonin transporter. However, its actions in human models of depression have not been assessed. Methods: This study explored the effects of acute administration of GSK424887 compared to placebo in healthy male volunteers. The selective serotonin reuptake inhibitor (SSRI) citalopram was used as a positive control. A battery of emotional processing tasks was given at the peak time of drug effect. Results: GSK424887 enhanced attentional vigilance in the dot-probe task to both positive and negative stimuli. By contrast, citalopram enhanced perception of angry, sad and happy facial expressions and increased positive bias in the facial expression recognition task. Neither drug significantly affected emotion potentiated startle responses or emotional memory. Conclusions: These results suggest that acute administration of GSK424887 modulated some aspects of emotional processing but these effects were not similar to those seen previously with antidepressant agents. This was the first use of the battery of emotional processing tasks in a Phase 1 study. Repeated administration of the test and active control drugs may be needed to reliably characterise their effects.