Objective assessment of motor activity in a clinical sample of adults with attention-deficit/hyperactivity disorder and/or cyclothymic temperament.

BACKGROUND: Most research on patterns of motor activity has been conducted on adults with mood disorders, but few studies have investigated comorbid attention-deficit/hyperactivity disorder (ADHD) or temperamental factors that may influence the clinical course and symptoms. Cyclothymic temperament (CT) is particularly associated with functional impairment. Clinical features define both disorders, but objective, biological markers for these disorders could give important insights with regard to pathophysiology and classification. METHODS: Seventy-six patients, requiring diagnostic evaluation of ADHD, mood or anxiety disorders were recruited. A comprehensive diagnostic evaluation, including the CT scale of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego - Auto-questionnaire (TEMPS-A), neuropsychological tests and actigraphy, was performed. ADHD was diagnosed according to the DSM-IV criteria. There was a range of different conditions in this clinical sample, but here we report on the presence of CT and ADHD in relation to motor activity. Twenty-nine healthy controls were recruited. We analyzed motor activity time series using linear and nonlinear mathematical methods, with a special focus on active and inactive periods in the actigraphic recordings. RESULTS: Forty patients fulfilled the criteria for ADHD, with the remainder receiving other psychiatric diagnoses (clinical controls). Forty-two patients fulfilled the criteria for CT. Twenty-two patients fulfilled the criteria for ADHD and CT, 18 patients met the criteria for ADHD without CT, and 15 patients had neither. The ratio duration of active/inactive periods was significantly lower in patients with CT than in patients without CT, in both the total sample, and in the ADHD subsample. CONCLUSIONS: CT is associated with objectively assessed changes in motor activity, implying that the systems regulating motor behavior in these patients are different from both healthy controls and clinical controls without CT. Findings suggest that actigraphy may supplement clinical assessments of CT and ADHD, and may provide an objective marker for CT.

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.