Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative.

BACKGROUND: Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. STRUCTURE: The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.com/ ) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants' response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. CONCLUSIONS: The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.

Validation of the Italian Version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN): Some Considerations on its Screening Usefulness.

INTRODUCTION: Abnormalities in biological rhythms (BR) may have a role in the pathophysiology of Bipolar Disorders (BD). The objective of this study is to validate the Italian version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), a useful tool in studying BR, and measure its accuracy in discriminating BD. METHODS: 44 outpatients with DSM-IV-TR diagnosis of BD and 38 controls balanced for sex and age were consecutively recruited. The discriminant validity of BRIAN for the screening of BD and its test re-test reliability in two evaluations were assessed. RESULTS: BD patients scored 22.22±11.19 in BRIAN against 7.13±5.6 of the control group (P<0.0001). BRIAN showed a good accuracy to screen between BD non-BD at cutoff 16, a sensitivity was 68.2 and specificity was 92.5. The test-retest stability measured using Pearson's coefficient found very high r values for each section and the total score, thus indicating a correlation at the two times of statistical significance in all measures. Cohen's Kappa varied from 0.47 in the sociality section to 0.80 in the sleep section, with a total K mean of 0.65. CONCLUSION: The results show that the Italian version of BRIAN has good discriminant validity in detecting BD from healthy controls and shows good test-retest reliability. The study suggests the possibility of developing mixed screening tools by introducing items on dysregulation of biological rhythms to the usual measures of mood.

The need for a behavioural science focus in research on mental health and mental disorders.

Psychology as a science offers an enormous diversity of theories, principles, and methodological approaches to understand mental health, abnormal functions and behaviours and mental disorders. A selected overview of the scope, current topics as well as strength and gaps in Psychological Science may help to depict the advances needed to inform future research agendas specifically on mental health and mental disorders. From an integrative psychological perspective, most maladaptive health behaviours and mental disorders can be conceptualized as the result of developmental dysfunctions of psychological functions and processes as well as neurobiological and genetic processes that interact with the environment. The paper presents and discusses an integrative translational model, linking basic and experimental research with clinical research as well as population-based prospective-longitudinal studies. This model provides a conceptual framework to identify how individual vulnerabilities interact with environment over time, and promote critical behaviours that might act as proximal risk factors for ill-health and mental disorders. Within the models framework, such improved knowledge is also expected to better delineate targeted preventive and therapeutic interventions that prevent further escalation in early stages before the full disorder and further complications thereof develop. In contrast to conventional "personalized medicine" that typically targets individual (genetic) variation of patients who already have developed a disease to improve medical treatment, the proposed framework model, linked to a concerted funding programme of the "Science of Behaviour Change", carries the promise of improved diagnosis, treatment and prevention of health-risk behaviour constellations as well as mental disorders.

Validity and Reliability of the Italian Version of the Functioning Assessment Short Test (FAST) in Bipolar Disorder.

BACKGROUND: Functioning Assessment Short Test (FAST) is a brief instrument designed to assess the main functioning problems experienced by psychiatric patients, specifically bipolar patients. It includes 24 items assessing impairment or disability in six domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time. The aim of this study is to measure the validity and reliability of the Italian version of this instrument. METHODS: Twenty-four patients with DSM-IV TR bipolar disorder and 20 healthy controls were recruited and evaluated in three private clinics in Cagliari (Sardinia, Italy). The psychometric properties of FAST (feasibility, internal consistency, concurrent validity, discriminant validity (patients vs controls and eutimic patients vs manic and depressed), and test-retest reliability were analyzed. RESULTS: The internal consistency obtained was very high with a Cronbach's alpha of 0.955. A highly significant negative correlation with GAF was obtained (r = -0.9; p < 0.001) pointing to a reasonable degree of concurrent validity. FAST show a good test-retest reliability between two independent evaluation differing of one week (mean K =0.73). The total FAST scores were lower in controls as compared with Bipolar Patients and in Euthimic patients compared with Depressed or Manic. CONCLUSION: The Italian version of the FAST showed similar psychometrics properties as far as regard internal consistency and discriminant validity of the original version and show a good test retest reliability measure by means of K statistics.

Long-term mental health resource utilization and cost of care following group psychoeducation or unstructured group support for bipolar disorders: a cost-benefit analysis.

OBJECTIVE: To explore the short- and long-term mental health resource utilization and cost of care in a sample of 120 individuals with bipolar disorders who participated in a randomized controlled efficacy trial of group psychoeducation versus unstructured group support. METHOD: Prospective, independent monitoring of DSM-IV bipolar disorder type I or II patients aged 18 to 65 years was conducted during the intervention phase (6 months) and follow-up phase (5-year postintervention) of a randomized controlled trial reporting clinical outcomes and inpatient and outpatient mental health service utilization, with estimation of cost of treatment per patient. The study was conducted from October 1997 through October 2006. RESULTS: Compared with individuals with bipolar disorder receiving the control intervention, psychoeducated patients had twice as many planned outpatient appointments, but the estimated mean cost of emergency consultation utilization was significantly less. There were trends for psychoeducated patients to opt for self-funded psychotherapy after completing group psychoeducation and to utilize more medications. However, inpatient care accounted for 40% estimated total cost in the control group but only about 15% in the psychoeducation group. CONCLUSIONS: This study demonstrates the importance of taking a long-term overview of the cost versus benefits of adjunctive psychological therapy in bipolar disorders. If viewed only in the short-term, the psychoeducation group used more mental health care resources without clear additional health gain. However, extended follow-up demonstrated a long-term advantage for psychoeducated individuals, such that, compared to an unstructured support group intervention, group psychoeducation is less costly and more effective.

Validity and reliability of the Functioning Assessment Short Test (FAST) in bipolar disorder.

BACKGROUND: Numerous studies have documented high rates of functional impairment among bipolar disorder (BD) patients, even during phases of remission. However, the majority of the available instruments used to assess functioning have focused on global measures of functional recovery rather than specific domains of psychosocial functioning. In this context, the Functioning Assessment Short Test (FAST) is a brief instrument designed to assess the main functioning problems experienced by psychiatric patients, particularly bipolar patients. It comprises 24 items that assess impairment or disability in six specific areas of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time. METHODS: 101 patients with DSM-IV TR bipolar disorder and 61 healthy controls were assessed in the Bipolar Disorder Program, Hospital Clinic of Barcelona. The psychometric properties of FAST (feasibility, internal consistency, concurrent validity, discriminant validity (euthymic vs acute patients), factorial analyses, and test-retest reliability) were analysed. RESULTS: The internal consistency obtained was very high with a Cronbach's alpha of 0.909. A highly significant negative correlation with GAF was obtained (r = -0.903; p < 0.001) pointing to a reasonable degree of concurrent validity. Test-retest reliability analysis showed a strong correlation between the two measures carried out one week apart (ICC = 0.98; p < 0.001). The total FAST scores were lower in euthymic (18.55 +/- 13.19; F = 35.43; p < 0.001) patients, as compared with manic (40.44 +/- 9.15) and depressive patients (43.21 +/- 13.34). CONCLUSION: The FAST showed strong psychometrics properties and was able to detect differences between euthymic and acute BD patients. In addition, it is a short (6 minutes) simple interview-administered instrument, which is easy to apply and requires only a short period of time for its application.

[Spanish version of a scale for the assessment of mania: validity and reliability of the Young Mania Rating Scale]. / Versión española de una escala de evaluación de la manía: validez y fiabilidad de la Escala de Young.

BACKGROUND: The Young Mania Rating Scale is the most widely used tool for the assessment of the intensity of manic symptoms. Unfortunately, to date, there was no Spanish validated version available. This study validated the Spanish version of the YMRS. PATIENTS AND METHOD: A sample of 541 DSM-IV manic or hypomanic bipolar patients were recruited in 56 different psychiatric settings in Spain and assessed with the YMRS by 112 clinicians specifically trained in its use on days 1, 7, 14, 30, 45 and at 3 and 6 months. The mania subscale of the Clinical Global Impression for Bipolar Disorders was also performed in order to have a standard measure to compare our results. Feasibility, reliability, validity and sensitivity of the YMRS were analysed. RESULTS: The YMRS Spanish version showed reliability index of 0.88 (internal consistency) and 0.76 (test-retest reliability), and good internal validity and external (p < 0.001) when compared to the mania subscale of the Modified Clinical Global Impression. The results also showed good sensitivity and feasibility. CONCLUSIONS: The YMRS Spanish Version is a useful, valid and reliable tool for the assessment of manic symptoms.