Bipolar 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.

Assess 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.

Two 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).

After treatment, patients receiving FR show better cognitive and psychosocial performance than those receiving TAU.

Given 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.

No significant relationships.

Bipolar disorder (BD) represents one of the most therapeutically complex psychiatric disorders. The development of a feasible comprehensive psychological approach to complement pharmacotherapy to improve its clinical management is required. The main objective of the present randomized controlled trial (RCT) was to test the efficacy of a novel adjunctive treatment entitled integrative approach in patients with BD, including: psychoeducation, mindfulness training, and functional remediation.

This is a parallel two-armed, rater-blind RCT of an integrative approach plus treatment as usual (TAU), v. TAU alone. Participants were recruited at the Hospital Clinic of Barcelona and randomized to one of the two conditions. They were assessed at baseline and after finishing the intervention. The main outcome variable included changes in psychosocial functioning assessed through the Functioning Assessment Short Test (FAST).

After finishing the treatment, the repeated-measures analyses revealed a significant group × time interaction in favor of the patients who received the integrative approach (n = 28) compared to the TAU group (n = 37) (Pillai's trace = 0.10; F(1,57) = 6.9; p = 0.01), improving the functional outcome. Significant effects were also found in two out of the six domains of the FAST, including the cognitive domain (Pillai's trace = 0.25; F(1,57) = 19.1; p < 0.001) and leisure time (Pillai's trace = 0.11; F(1,57) = 7.15; p = 0.01). Regarding the secondary outcomes, a significant group × time interaction in Hamilton Depression Rating Scale changes was detected (Pillai's trace = 0.08; F(1,62) = 5.6; p = 0.02).

This preliminary study suggests that the integrative approach represents a promising cost-effective therapy to improve psychosocial functioning and residual depressive symptoms in patients suffering from BD.

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.

Functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients.

A total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants’ neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients.

Patients receiving functional remediation (n = 56) showed an improvement on delayed free recall when compared with the TAU (n = 63) and psychoeducation (n = 69) groups as shown by the group × time interaction at 6-month follow-up [F2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU (p = 0.04), but not with psychoeducation (p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome (F2,158 = 4.26, df = 2, p = 0.016).

Functional remediation is effective at improving verbal memory and psychosocial functioning in a sample of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation.