Functional Remediation Research Articles

Study protocol - elucidating the neural correlates of functional remediation for older adults with bipolar disorder.

Beyond mood abnormalities, bipolar disorder (BD) includes cognitive impairments that worsen psychosocial functioning and quality of life. These deficits are especially severe in older adults with BD (OABD), a condition expected to represent most individuals with BD in the upcoming years. Restoring the psychosocial functioning of this population will thus soon represent a public health priority. To help tackle the problem, the Bipolar and Depressive Disorders Unit at the Hospital Clínic of Barcelona has recently adapted its Functional Remediation (FR) program to that population, calling it FROA-BD. However, while scarce previous studies localize the neural mechanisms of cognitive remediation interventions in the dorsal prefrontal cortex, the specific mechanisms are seldom unknown. In the present project, we will investigate the neural correlates of FR-OABD to understand its mechanisms better and inform for potential optimization. The aim is to investigate the brain features and changes associated with FROA-BD efficacy. Thirty-two individuals with OABD in full or partial remission will undergo a magnetic resonance imaging (MRI) session before receiving FR-OABD. After completing the FR-OABD intervention, they will undergo another MRI session. The MRI sessions will include structural, diffusion-weighted imaging (DWI), functional MRI (fMRI) with working memory (n-back) and verbal learning tasks, and frontal spectroscopy. We will correlate the pre-post change in dorsolateral and dorsomedial prefrontal cortices activation during the n-back task with the change in psychosocial functioning [measured with the Functioning Assessment Short Test (FAST)]. We will also conduct exploratory whole-brain correlation analyses between baseline or pre-post changes in MRI data and other clinical and cognitive outcomes to provide more insights into the mechanisms and explore potential brain markers that may predict a better treatment response. We will also conduct separate analyses by sex. The results of this study may provide insights into how FROA-BD and other cognitive remediations modulate brain function and thus could optimize these interventions.

Efficacy of Functional Remediation on Cognitive and Psychosocial Functioning in Patients with Bipolar Disorder: Study Protocol for a Randomized Controlled Study.

Neurocognitive impairment is a prominent characteristic of bipolar disorder (BD), linked with poor psychosocial functioning. This study's purpose is to evaluate the effectiveness of functional remediation (FR) in enhancing neurocognitive dysfunctions in a sample of remitted patients with diagnosis of BD in comparison to treatment as usual-TAU. To quantify the neurocognitive damage, the Brief Assessment of Cognition in Affective Disorders (BAC-A) will be used, and the overall psychosocial functioning will be measured with the Functioning Assessment Short Test-FAST. The randomized, rater-blinded, controlled study will include two arms (1:1) encompassing 54 outpatients with diagnosis of BD-I and BD-II, as defined by the DSM-5 criteria. In the experimental phase, remitted patients aged 18-55 years will be involved. At the baseline, at the end of intervention and at the 6-month follow-up, patients will be evaluated using clinical scales (Young Mania Rating Scale (Y-MRS) and Hamilton Depression Rating Scale (HAM-D)). Neurocognitive measurements and psychosocial functioning will be valued, respectively, with BAC-A and FAST. The primary expected outcome is that following FR intervention, patients will exhibit improved cognitive abilities and psychosocial outcomes compared to the participants in the TAU group. It is now recognized that neurocognitive deficits are potential predictors of functional outcome in patients with BD. In recent years, there has been a growing interest in the implementation of interventions that, in addition to symptomatic remission, are also aimed at neurocognitive dysfunctions in order to achieve a recovery of psychosocial functioning.

Neurotrophics correlates and functional remediation in bipolar disorder. A pilot study

IntroductionBipolar disorder (BD) is a complex mental disorder. Cognitive dysfunction represents a core feature, strongly related with patients’ functional outcome. Functional Remediation (FR), is an integrated neuropsychological and psychosocial rehabilitation treatment aimed at enhancing cognitive functions in order to achieve full functional recovery(Torrent et al., 2013). Evidence highlighted an association of neurotrophins and cognitive dysfunctions. Particularly, BDNF has been investigated a potential biomarker. Preliminary studies explored the effects induced through FR interventions on serum BDNF levels(Bonnin et al., 2019). Evidences suggest that high BDNF serum levels are related to good cognitive functioning(Mora et al., 2019). Results require further explorations. The present pilot study targets to identify the neurobiological correlates of response, investigating the potential neuroprotective role of the FR.ObjectivesAssess the effectiveness of FR in ameliorate cognitive deficits measured with BAC-A and psychosocial functioning with FAST, in modifying BDNF levels in a sample of euthymic patients with BD, compared to standard treatment.MethodsTwo arms(1:1)randomized, rater-blinded, controlled study of 30out-patients with BD-I and BD-II, according to DSM-5 criteria. Patients between 18 and 55 years in euthymic phase. Neurocognitive and clinical assessments, at the same times, serum assessment of BDNF levels will be performed.All patients will be assessed at baseline(T0), at the end of treatment(T1) and at the 3-month follow-up(T2).ResultsAfter treatment, patients receiving FR show better cognitive and psychosocial performance than those receiving TAU.ConclusionsGiven the important role of neutrophins in the pathogenesis of BD, identifying BD-specific biomarkers would contribute to understand the underlying neuro-pathophysiological processes and to personalize treatments.DisclosureNo significant relationships.

Long-term outcome predictors after functional remediation in patients with bipolar disorder.

Improving functioning in patients with bipolar disorder (BD) is one of the main objectives in clinical practice. Of the few psychosocial interventions that have been specifically developed to enhance the psychosocial outcome in BD, functional remediation (FR) is one which has demonstrated efficacy. The aim of this study was to examine which variables could predict improved functional outcome following the FR intervention in a sample of euthymic or subsyndromal patients with BD. A total of 92 euthymic outpatients were included in this longitudinal study, with 62 completers. Partial correlations controlling for the functional outcome at baseline were calculated between demographic, clinical and neurocognitive variables, and functional outcome at endpoint was assessed by means of the Functioning Assessment Short Test scale. Next, a multiple regression analysis was run in order to identify potential predictors of functional outcome at 2-year follow-up, using the variables found to be statistically significant in the correlation analysis and other variables related to functioning as identified in the previous scientific literature. The regression model revealed that only two independent variables significantly contributed to the model (F(6,53): 4.003; p = 0.002), namely verbal memory and inhibitory control. The model accounted for 31.2% of the variance. No other demographic or clinical variable contributed to the model. Results suggest that patients with better cognitive performance at baseline, especially in terms of verbal memory and executive functions, may present better functional outcomes at long term follow-up after receiving functional remediation.

CHALLENGES AND OPPORTUNITIES WITH POLYGENIC RISK SCORES IN PSYCHIATRY

The main aim of this study is to evaluate the impact of functional remediation (FR) in serum brain derived neurotrophic factor (BDNF) levels in euthymic adult patients with Bipolar Disorder (BD). A total of 128 participants were recruited at the Hospital Clinic of Barcelona. They were assessed at baseline and at the end of follow-up by the means of Hamilton Depression Scale (HAM-D), Young Mania Rating Scale (YMRS) and Functioning Assessment Short Test (FAST), as well as a clinical structured interview to collect clinical and demographic variables of interest. Blood samples were also collected to assess BDNF levels. After baseline assessment, patients received FR, Psychoeducation or treatment as usual (TAU).One hundred and two out of 126 participants finished the study distributed as follows: FR group (n = 39); Psychoeducation group (n = 47) and TAU group (n = 16). Longitudinal repeated-measures analyses addressing the treatment effect on BDNF levels showed non-significant differences between the three groups (Pillai's trace = 0.06; F(2,97)= 0.28; p = 0.75), suggesting no interaction between treatment allocation and time on BDNF levels. The results of this study suggest that FR has no effect on peripheral BDNF levels in euthymic patients with BD, despite the improvement in psychosocial functioning.

The effects of cognitive remediation on cognitive abilities and real-world functioning among people with bipolar disorder: A systematic review: Special Section on “Translational and Neuroscience Studies in Affective Disorders”. Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders.

BackgroundBipolar disorder (BD) is characterized by cognitive impairments that are known to predict psychosocial functioning and quality of life. While cognitive remediation (CR) was originally developed to directly target cognitive symptoms in traumatic brain injury and psychotic illnesses, the efficacy of CR in BD has begun to emerge only in the last decade. Functional Remediation (FR) is an integrated intervention that has been developed to restore psychosocial functioning by means of ecological neurocognitive techniques that involve psychoeducation about cognitive dysfunctions and their impact on the general functioning. Because of the heterogeneity of treatment targets and mechanisms of actions, here we aim to illustrate the effects induced by existing CR/FR approaches in BD. MethodsIn this systematic review, we evaluated cognitive and functional outcomes after CR/FR in studies conducted in BD. ResultsEleven studies met inclusion criteria: 3 RCTs that compared CR/FR to one or more control condition (n = 354), 5 secondary analyses that further examined data from these trials, 2 single-arm studies, and 1 naturalistic study. While features such as the use of computerized training tools and a group-based format recurred across studies, CR/FR paradigms targeting different cognitive and functional domains showed specificity of training focus to outcomes. Effect sizes were in the medium-large range, suggesting that patients with BD respond to treatment at or above the level reported in psychotic patients. Integrated approaches that combined cognitive exercises with group-based experiences were associated with both cognitive and functional improvements. ConclusionsIn this review, we found support for the use of CR/FR paradigms in patients with BD with evidence of cognitive and functional improvements. The scarcity of currently published RCTs as well as of data examining mechanisms of action and neural correlates limits the generalizability of our findings.

Functional remediation improves bipolar disorder functioning with no effects on brain-derived neurotrophic factor levels

The main aim of this study is to evaluate the impact of functional remediation (FR) in serum brain derived neurotrophic factor (BDNF) levels in euthymic adult patients with Bipolar Disorder (BD). A total of 128 participants were recruited at the Hospital Clinic of Barcelona. They were assessed at baseline and at the end of follow-up by the means of Hamilton Depression Scale (HAM-D), Young Mania Rating Scale (YMRS) and Functioning Assessment Short Test (FAST), as well as a clinical structured interview to collect clinical and demographic variables of interest. Blood samples were also collected to assess BDNF levels. After baseline assessment, patients received FR, Psychoeducation or treatment as usual (TAU).One hundred and two out of 126 participants finished the study distributed as follows: FR group (n = 39); Psychoeducation group (n = 47) and TAU group (n = 16). Longitudinal repeated-measures analyses addressing the treatment effect on BDNF levels showed non-significant differences between the three groups (Pillai's trace = 0.06; F(2,97)= 0.28; p = 0.75), suggesting no interaction between treatment allocation and time on BDNF levels. The results of this study suggest that FR has no effect on peripheral BDNF levels in euthymic patients with BD, despite the improvement in psychosocial functioning.

Testing the efficacy of INtegral Cognitive REMediation (INCREM) in major depressive disorder: study protocol for a randomized clinical trial

BackgroundGiven the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life.MethodsA single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR + CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110 min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes.DiscussionTo our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR + CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning.Trial registrationClinical Trials NCT03624621. Date registered 10th of August 2018 and last updated 24th August 2018.

Functional remediation for patients with bipolar II disorder: Improvement of functioning and subsyndromal symptoms

Recently, Functional Remediation (FR) has proven to be effective in improving the functional outcome of euthymic bipolar patients. The aim of this study was to test the efficacy of the FR program in a subsample of euthymic bipolar II patients (BPII). A post-hoc analyses were undertaken using data of 53 BPII outpatients who had participated in a multicenter, rater-blind, randomized, controlled trial exploring the efficacy of FR (n=17) as compared with a Psychoeducation group (PSY) (n=19) and a treatment as usual control group (TAU n=17). The primary outcome variable was the functional improvement defined as the mean change in the Functioning Assessment Short Test (FAST) from baseline to endpoint after the intervention. Regarding the treatment effect, data reveal a significant functional improvement from baseline to endpoint, suggestive for an interaction between program pertinence and time (pre-post). Nevertheless, Tukey׳s post-hoc test only revealed a trend in favor of a better outcome for FR when compared to the other two groups. We also found an interaction between program pertinence and time when analysing the subdepressive symptoms, with BPII patients in FR showing a significant reduction when compared to the PSY group. Our results suggest that the FR appears to be effective in improving the overall functional outcome in BPII, as well as in reducing subdepressive symptoms.

EPA-0492 - Functional remediation in bipolar II patients: improvement of functioning and subsyndromal symptoms

Introduction Recently, Functional Remediation (FR) has proven to be effective in improving the functional outcome of euthymic bipolar patients. Objective Our objective was to test the efficacy of FR programme in a subsample of euthymic bipolar II patients (BPII). Aims The main aim was improve the functional outcome in these patients. Method Post-hoc analyses were undertaken using data of 53 DSM-IV diagnosed BPII outpatients who had participated in a multicentre, rater blind, randomized, controlled trial (RCT) exploring the efficacy of FR (n=17) as compared with a Psychoeducation (PSY) (n=19) and a control (n=17) groups which only treatment as usual (TAU). The primary outcome variable was a functional improvement measured as the mean change in the Functioning Assessment Short Test (FAST) from baseline to endpoint after intervention. Results Data revealed a significant functional improvement from baseline to endpoint (Pillai's Trace =0.164; F =3.619; p =0.037), suggestive for an interaction between program pertinence and time (pre-post). Nevertheless, Tukey's post-hoc test only revealed a trend in favour of a better outcome for FR when compared to the TAU (p =0.058) and to the PSY group (p =0.062). We also found an interaction between program pertinence and time when analysing the subdepressive symptoms (Pillai's Trace =0.157; F =3.635; p =0.036), so that patients in FR showed a significant reduction in subdepressive symptomatology when compared to the PSY group (p= 0.041). Conclusions The FR program appears to be effective in improving the overall functional outcome in BPII patients, as well as in reducing subdepressive symptoms.