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  • From neuroscience to evidence based psychological treatments - The promise and the challenge, ECNP March 2016, Nice, France.

    3 July 2018

    This ECNP meeting was designed to build bridges between different constituencies of mental illness treatment researchers from a range of backgrounds with a specific focus on enhancing the development of novel, evidence based, psychological treatments. In particular we wished to explore the potential for basic neuroscience to support the development of more effective psychological treatments, just as this approach is starting to illuminate the actions of drugs. To fulfil this aim, a selection of clinical psychologists, psychiatrists and neuroscientists were invited to sit at the same table. The starting point of the meeting was the proposition that we know certain psychological treatments work, but we have only an approximate understanding of why they work. The first task in developing a coherent mental health science would therefore be to uncover the mechanisms (at all levels of analysis) of effective psychological treatments. Delineating these mechanisms, a task that will require input from both the clinic and the laboratory, will provide a key foundation for the rational optimisation of psychological treatments. As reviewed in this paper, the speakers at the meeting reviewed recent advances in the understanding of clinical and cognitive psychology, neuroscience, experimental psychopathology, and treatment delivery technology focussed primarily on anxiety disorders and depression. We started by asking three rhetorical questions: What has psychology done for treatment? What has technology done for psychology? What has neuroscience done for psychology? We then addressed how research in five broad research areas could inform the future development of better treatments: Attention, Conditioning, Compulsions and addiction, Emotional Memory, and Reward and emotional bias. Research in all these areas (and more) can be harnessed to neuroscience since psychological therapies are a learning process with a biological basis in the brain. Because current treatment approaches are not fully satisfactory, there is an imperative to understand why not. And when psychological therapies do work we need to understand why this is the case, and how we can improve them. We may be able to improve accessibility to treatment without understanding mechanisms. But for treatment innovation and improvement, mechanistic insights may actually help. Applying neuroscience in this way will become an additional mission for ECNP.

  • The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial.

    3 July 2018

    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.

  • Depression and Violence in Adolescence and Young Adults: Findings From Three Longitudinal Cohorts.

    3 July 2018

    OBJECTIVE: Despite recent research demonstrating associations between violence and depression in adults, links in adolescents are uncertain. This study aims to assess the longitudinal associations between young people's depression and later violent outcomes. METHOD: We used data from three cohorts with different measurements of depression exposures and subsequent violent outcomes. In a Dutch community cohort Research on Adolescent Development And Relationships (RADAR; N = 623) and a population-based British birth cohort Avon Longitudinal Study of Parents and Children (ALSPAC; N = 4,030), we examined the longitudinal links between adolescent depressive symptoms and violent behaviors from age 13 to 17 years. In a total Finnish birth cohort (FBC 1987; N = 57,526), we estimated risk of violent convictions in individuals clinically diagnosed with depression from age 15 to 27 years. RESULTS: During a mean follow-up period of 4 years, the adjusted odds ratio (aOR) of violent behaviors per unit of increase in depressive symptoms was 1.7 (95% CI = 1.2-2.5) in the Dutch RADAR community sample and 1.8 (95% CI = 1.4-2.3) in the British ALSPAC birth cohort. In the FBC 1987 cohort, the aOR of violent convictions was 2.1 (95% CI = 1.7-2.7) among individuals with a depression diagnosis compared with general population controls without depression. All risk estimates were adjusted for family socioeconomic status and previous violence. CONCLUSION: Consistent findings across three longitudinal studies suggest that clinical guidelines should consider recommending risk assessment for violence in young people with depression. The benefits of targeting risk management in subgroups by gender need further investigation.

  • Clinical Insight Into Latent Variables of Psychiatric Questionnaires for Mood Symptom Self-Assessment.

    3 July 2018

    BACKGROUND: We recently described a new questionnaire to monitor mood called mood zoom (MZ). MZ comprises 6 items assessing mood symptoms on a 7-point Likert scale; we had previously used standard principal component analysis (PCA) to tentatively understand its properties, but the presence of multiple nonzero loadings obstructed the interpretation of its latent variables. OBJECTIVE: The aim of this study was to rigorously investigate the internal properties and latent variables of MZ using an algorithmic approach which may lead to more interpretable results than PCA. Additionally, we explored three other widely used psychiatric questionnaires to investigate latent variable structure similarities with MZ: (1) Altman self-rating mania scale (ASRM), assessing mania; (2) quick inventory of depressive symptomatology (QIDS) self-report, assessing depression; and (3) generalized anxiety disorder (7-item) (GAD-7), assessing anxiety. METHODS: We elicited responses from 131 participants: 48 bipolar disorder (BD), 32 borderline personality disorder (BPD), and 51 healthy controls (HC), collected longitudinally (median [interquartile range, IQR]: 363 [276] days). Participants were requested to complete ASRM, QIDS, and GAD-7 weekly (all 3 questionnaires were completed on the Web) and MZ daily (using a custom-based smartphone app). We applied sparse PCA (SPCA) to determine the latent variables for the four questionnaires, where a small subset of the original items contributes toward each latent variable. RESULTS: We found that MZ had great consistency across the three cohorts studied. Three main principal components were derived using SPCA, which can be tentatively interpreted as (1) anxiety and sadness, (2) positive affect, and (3) irritability. The MZ principal component comprising anxiety and sadness explains most of the variance in BD and BPD, whereas the positive affect of MZ explains most of the variance in HC. The latent variables in ASRM were identical for the patient groups but different for HC; nevertheless, the latent variables shared common items across both the patient group and HC. On the contrary, QIDS had overall very different principal components across groups; sleep was a key element in HC and BD but was absent in BPD. In GAD-7, nervousness was the principal component explaining most of the variance in BD and HC. CONCLUSIONS: This study has important implications for understanding self-reported mood. MZ has a consistent, intuitively interpretable latent variable structure and hence may be a good instrument for generic mood assessment. Irritability appears to be the key distinguishing latent variable between BD and BPD and might be useful for differential diagnosis. Anxiety and sadness are closely interlinked, a finding that might inform treatment effects to jointly address these covarying symptoms. Anxiety and nervousness appear to be amongst the cardinal latent variable symptoms in BD and merit close attention in clinical practice.

  • The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Acute and long-term treatment of mixed states in bipolar disorder.

    3 July 2018

    OBJECTIVES: Although clinically highly relevant, the recognition and treatment of bipolar mixed states has played only an underpart in recent guidelines. This WFSBP guideline has been developed to supply a systematic overview of all scientific evidence pertaining to the acute and long-term treatment of bipolar mixed states in adults. METHODS: Material used for these guidelines is based on a systematic literature search using various data bases. Their scientific rigour was categorised into six levels of evidence (A-F), and different grades of recommendation to ensure practicability were assigned. We examined data pertaining to the acute treatment of manic and depressive symptoms in bipolar mixed patients, as well as data pertaining to the prevention of mixed recurrences after an index episode of any type, or recurrence of any type after a mixed index episode. RESULTS: Manic symptoms in bipolar mixed states appeared responsive to treatment with several atypical antipsychotics, the best evidence resting with olanzapine. For depressive symptoms, addition of ziprasidone to treatment as usual may be beneficial; however, the evidence base is much more limited than for the treatment of manic symptoms. Besides olanzapine and quetiapine, valproate and lithium should also be considered for recurrence prevention. LIMITATIONS: The concept of mixed states changed over time, and recently became much more comprehensive with the release of DSM-5. As a consequence, studies in bipolar mixed patients targeted slightly different bipolar subpopulations. In addition, trial designs in acute and maintenance treatment also advanced in recent years in response to regulatory demands. CONCLUSIONS: Current treatment recommendations are still based on limited evidence, and there is a clear demand for confirmative studies adopting the DSM-5 specifier with mixed features concept.

  • Dynamic Imaging of the Eye, Optic Nerve, and Extraocular Muscles With Golden Angle Radial MRI.

    3 July 2018

    Purpose: The eye and its accessory structures, the optic nerve and the extraocular muscles, form a complex dynamic system. In vivo magnetic resonance imaging (MRI) of this system in motion can have substantial benefits in understanding oculomotor functioning in health and disease, but has been restricted to date to imaging of static gazes only. The purpose of this work was to develop a technique to image the eye and its accessory visual structures in motion. Methods: Dynamic imaging of the eye was developed on a 3-Tesla MRI scanner, based on a golden angle radial sequence that allows freely selectable frame-rate and temporal-span image reconstructions from the same acquired data set. Retrospective image reconstructions at a chosen frame rate of 57 ms per image yielded high-quality in vivo movies of various eye motion tasks performed in the scanner. Motion analysis was performed for a left-right version task where motion paths, lengths, and strains/globe angle of the medial and lateral extraocular muscles and the optic nerves were estimated. Results: Offline image reconstructions resulted in dynamic images of bilateral visual structures of healthy adults in only ∼15-s imaging time. Qualitative and quantitative analyses of the motion enabled estimation of trajectories, lengths, and strains on the optic nerves and extraocular muscles at very high frame rates of ∼18 frames/s. Conclusions: This work presents an MRI technique that enables high-frame-rate dynamic imaging of the eyes and orbital structures. The presented sequence has the potential to be used in furthering the understanding of oculomotor mechanics in vivo, both in health and disease.

  • Quantitative characterization of optic nerve atrophy in patients with multiple sclerosis.

    3 July 2018

    BACKGROUND: Optic neuritis (ON) is one of the most common presentations of multiple sclerosis (MS). Magnetic resonance imaging (MRI) of the optic nerves is challenging because of retrobulbar motion, orbital fat and susceptibility artifacts from maxillary sinuses; therefore, axonal loss is investigated with the surrogate measure of a single heuristically defined point along the nerve as opposed to volumetric investigation. OBJECTIVE: The objective of this paper is to derive optic nerve volumetrics along the entire nerve length in patients with MS and healthy controls in vivo using high-resolution, clinically viable MRI. METHODS: An advanced, isotropic T2-weighted turbo spin echo MRI was applied to 29 MS patients with (14 patients ON+) or without (15 patients ON-) history of ON and 42 healthy volunteers. An automated tool was used to estimate and compare whole optic nerve and surrounding cerebrospinal fluid radii along the length of the nerve. RESULTS AND CONCLUSION: Only ON+ MS patients had a significantly reduced optic nerve radius compared to healthy controls in the central segment of the optic nerve. Using clinically available MRI methods, we show and quantify ON volume loss for the first time in MS patients.