Adriane Ribeiro Rosa

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes.

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p=0.019) and depressed (p=0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r=-0.37, p=0.005) and depressive (r=-0.30, p=0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.

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

BackgroundNumerous 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.Methods101 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.ResultsThe internal consistency obtained was very high with a Cronbachs 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).ConclusionThe 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.

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Clinical predictors of functional outcome of bipolar patients in remission.

OBJECTIVES A number of studies have now shown that subjects with bipolar disorder (BD) have significant psychosocial impairment during interepisode intervals. This study was carried out to assess the level of functioning as well as to identify potential predictors of functioning in a well-defined, euthymic bipolar sample. METHODS The study included 71 euthymic bipolar patients and 61 healthy controls. The Functioning Assessment Short Test (FAST) was used to assess multiple areas of functioning such as autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time. Multivariate analysis was used to determine the global and specific clinical predictors of outcome. RESULTS Sixty percent (n = 42) of the patients had overall functional impairment (defined as a FAST total score > 11) compared to 13.1% (n = 8) of the control group (p = 0.001). Bipolar patients showed a worse functioning in all the areas of the FAST. Only four variables-older age, depressive symptoms, number of previous mixed episodes, and number of previous hospitalizations-were associated with poor functioning, on a linear regression model, which accounted for 44% of the variance (F = 12.54, df = 58, p < 0.001). CONCLUSIONS A substantial proportion of bipolar patients experience unfavorable functioning, suggesting that there is a significant degree of morbidity and dysfunction associated with BD, even during remission periods. Previous mixed episodes, current subclinical depressive symptoms, previous hospitalizations, and older age were identified as significant potential clinical predictors of functional impairment.

Functional Impairment and Disability across Mood States in Bipolar Disorder

BACKGROUND Bipolar disorder (BD) represents a chronic and recurrent illness that can lead to severe disruptions in family, social, and occupational functioning. The severity of mood symptomatology has been associated with functional impairment in this population. However, the majority of studies have assessed global functioning without considering specific domains. The main objective of the current study was to assess specific life domains of functioning as well as the overall functioning in patients with BD across different mood states ([hypo] mania, depression, or euthymia) compared with healthy controls by the means of a standardized scale validated for BD. METHODS The sample included 131 subjects with BD (68 in remission, 31 hypo [manic], and 32 depressed) and 61 healthy controls. The Functioning Assessment Short Test was used to assess overall and multiple areas of functional impairment (autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time). RESULTS The results showed significant intergroup differences; depressed patients had the lowest functioning (48.03 ± 12.38) followed by (hypo) manic patients (39.81 ± 13.99). The euthymic group showed least impairment in functioning compared with the depression and (hypo) mania groups (11.76 ± 12.73) but still displayed significant impairment when compared with the healthy control group (5.93 ± 4.43). CONCLUSIONS This study indicates that depressive symptoms are associated with greater negative impact on psychosocial functioning than (hypo) manic symptoms. Further deficits in functioning seem to persist during remission. The results highlight the importance of aggressively treating depression and mania and the need to develop psychosocial interventions targeting to improve functional outcomes.

Long-term outcome of cognitive impairment in bipolar disorder.

OBJECTIVE To evaluate the longitudinal course and outcome of cognitive deficits and their clinical correlates in bipolar disorder. METHOD One hundred thirteen participants (68 patients and 45 healthy controls) were assessed by the means of a neuropsychological battery targeting attention, psychomotor speed, verbal memory, and executive functions at baseline: 68 euthymic outpatients with a DSM-IV diagnosis of bipolar disorder (53 bipolar I and 15 bipolar II) were enrolled at the Bipolar Disorder Unit of the Hospital Clinic of Barcelona. Forty-five patients completed the follow-up. The assessments started in February 1999 and finished in July 2010. The primary outcome of the study was the change in the neuropsychological performance in the patient group. RESULTS Repeated-measures analyses showed significant effects of time in 2 cognitive domains: attention and executive functions. Attention slightly improved (P = .043) but executive function worsened (P = .001). Regression analyses showed that the duration of illness and baseline subdepressive symptoms were associated with poor performance in executive function. Subdepressive symptoms at endpoint were associated with poor functioning. The best predictor of low functioning was verbal memory dysfunction at baseline. CONCLUSIONS The cognitive impairment remained stable across the follow-up period in many measures assessed except for a worsening of executive measures, which have been found to be associated with the duration of illness and subdepressive symptoms.

Clinical staging in bipolar disorder: focus on cognition and functioning.

OBJECTIVE Clinical staging has increasingly been considered suitable for psychiatric disorders such as bipolar disorder. A staging model of bipolar disorder could help clinicians understand the mechanisms underlying the course of the illness and guide prognosis and therapy. This study aimed to investigate differences in functional status and cognitive functioning in patients in different clinical stages of bipolar disorder. METHOD Subjects who met DSM-IV criteria for bipolar disorder (n = 54) were recruited from the Bipolar Disorders Program at Hospital de Clínicas de Porto Alegre (Brazil) from October 2012 to October 2013. All patients had been in remission (score < 7 on the 17-item HDRS and the YMRS) for at least 1 month before assessment. They were classified into 4 clinical stages according to the model described by Kapczinski et al and compared to 43 healthy controls. Functional status was assessed by using the Functioning Assessment Short Test (FAST). Neuropsychological measures were performed to investigate cognitive functioning. RESULTS Significant differences in functional status were found between patients in all stages compared to controls (F = 33.014, P < .001), except for stage I (P = .104). Additionally, a very strong linear association was found between FAST scores and clinical stages, with FAST scores increasing from stage I to IV (F = 149.55, P < .001). In the bipolar group, stage I was associated with better occupational functioning than stage II (F = 48.344, P = .003). Stage IV patients experienced greater impairment in autonomy than stage III patients (F = 26.646, P = .004), and stage III patients experienced poorer autonomy than those in stage II (P = .004). With regard to cognitive measures, patients in late stages (stages III and IV) were more impaired than healthy controls (P < .001). A similar performance was found between patients in early stages (stages I and II) and healthy controls. DISCUSSION This study showed progressive functional changes from stage I to stage IV of bipolar disorder, with a greater impairment in patients in later stages of the illness. FAST scores seem to have a good discriminant ability to distinguish between patients in early versus late stages of bipolar disorder and could therefore contribute to the development of a bipolar disorder staging system.

Increased serum glial cell line-derived neurotrophic factor immunocontent during manic and depressive episodes in individuals with bipolar disorder

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor beta family, which plays a role in the development and function of hippocampal cells. Preclinical studies suggest that changes in neurotrophic growth factor systems might be involved in the pathophysiology of mood disorders including bipolar disorder (BD) [E.J. Nestler, M. Barrot, R.J. DiLeone, A.J. Eisch, S.J. Gold, L.M. Monteggia, Neurobiology of depression, Neuron 34 (2002) 13-25]. This is the first study to analyze GDNF immunocontent in BD subjects across different mood states, including mania, depression, and remission (euthymia). Fourty-four bipolar patients (14 depressed, 15 manic, and 15 euthymic) and 14 healthy controls, diagnosed according to the Structural Clinical Interview for DSM-IV were studied. Serum GDNF immunocontent was measured using Western blotting. Serum GDNF immunocontent was increased in manic (F=42.31; p=0.001; one-way ANOVA) and depressed (F=42.31; p=0.004; one-way ANOVA) bipolar patients, but not in euthymic patients as compared with controls. Our results indicate that changes in GDNF immunocontent occur during acute major affective episodes in bipolar subjects. These results further support the role of neurotrophins in the pathophysiology of bipolar disorder. Whether the observed increase in GDNF immunocontent correspond to a pathological or an adaptive response remains to be determined.

Gender differences in a cohort study of 604 bipolar patients: The role of predominant polarity

BACKGROUND Some clinical differences between gender regarding the course and outcome of bipolar disorders have already been described and some others remain still controversial. AIMS To explore gender differences regarding clinical and socio-demographic characteristics amongst bipolar patients with particular attention to predominant polarity and depressive symptoms. METHOD Data were collected from DSM-IV type I and II bipolar patients (n=604), resulting from the systematic follow-up of the Bipolar Disorders Program, Hospital Clinic of Barcelona, over an average follow-up of 10 years. Socio-demographic and clinical variables were collected in order to detect gender-related differences. RESULTS Bipolar women are more likely than men to show a predominance of depressive polarity as well as a depressive onset whilst men would be more likely to suffer from comorbid substance use disorders. Women significantly have a higher lifetime prevalence of psychotic depression and a higher prevalence of axis II comorbid disorders. Bipolar women are also more likely to have a family history of suicide and a lifetime history of attempted suicide. Suicide attempts are more often violent amongst bipolar men. In a backward logistic regression model, two variables were responsible for most gender-related clinical differences: type of predominant polarity - more likely to be depressive amongst women - (B=-0.794, p=0.027, Exp(B)=0.452; CI= 0.223-0.915), alcohol abuse (B=-1.095, p=0.000, Exp(B)=2990; CI= 1.817-4.919) and cocaine abuse (B=0.784, p=0.033, Exp(B)=2.189; CI= 1.066-4.496) - more prevalent amongst men. CONCLUSION The main characteristic featuring bipolar women is depression, both at illness onset and as a predominant polarity all along the illness course. This may have important diagnostic and therapeutic implications.

Development and use of a biological rhythm interview.

INTRODUCTION As several lines of evidence point to irregular biological rhythms in bipolar disorder, and its disruption may lead to new illness episodes, having an instrument that measures biological rhythms is critical. This report describes the validation of a new instrument, the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), designed to assess biological rhythms in the clinical setting. METHODS Eighty-one outpatients with a diagnosis of bipolar disorder and 79 control subjects matched for type of health service used, sex, age and educational level were consecutively recruited. After a pilot study, 18 items evaluating sleep, activities, social rhythm and eating pattern were probed for discriminant, content and construct validity, concurrent validity with the Pittsburgh Sleep Quality Index (PSQI), internal consistency and test-retest reliability. RESULTS A three-factor solution, termed sleep/social rhythm factor, activity factor and feeding factor, provided the best theoretical and most parsimonious account of the data; items essentially loaded in factors as theoretically intended, with the exception of the sleep and social scales, which formed a single factor. Test-retest reliability and internal consistency were excellent. Highly significant differences between the two groups were found for the whole scale and for each BRIAN factor. Total BRIAN scores were highly correlated with the global PSQI score. DISCUSSION The BRIAN scale presents a consistent profile of validity and reliability. Its use may help clinicians to better assess their patients and researchers to improve the evaluation of the impact of novel therapies targeting biological rhythm pathways.