Sara Barbeito

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.

Cannabis and First-Episode Psychosis: Different Long-term Outcomes Depending on Continued or Discontinued Use

Objective: To examine the influence of cannabis use on long-term outcome in patients with a first psychotic episode, comparing patients who have never used cannabis with (a) those who used cannabis before the first episode but stopped using it during follow-up and (b) those who used cannabis both before the first episode and during follow-up. Methods: Patients were studied following their first admission for psychosis. They were interviewed at years 1, 3, and 5. At follow-up after 8 years, functional outcome and alcohol and drug abuse were recorded. Patients were classified according to cannabis use: 25 had cannabis use before their first psychotic episode and continuous use during follow-up (CU), 27 had cannabis use before their first episode but stopped its use during follow-up (CUS), and 40 never used cannabis (NU). Results: The 3 groups did not differ significantly in symptoms or functional outcome at baseline or during short-term follow-up. The CUS group exhibited better long-term functional outcome compared with the other 2 groups and had fewer negative symptoms than the CU group, after adjusting for potential confounders. For the CUS group, the effect size was 1.26 (95% confidence interval [CI] = 0.65 to 1.86) for functional outcome and −0.72 (95% CI = −1.27 to −0.14) for negative symptoms. All patients experienced improvements in positive symptoms during long-term follow-up. Conclusion: Cannabis has a deleterious effect, but stopping use after the first psychotic episode contributes to a clear improvement in outcome. The positive effects of stopping cannabis use can be seen more clearly in the long term.

Poor Long-Term Prognosis in Mixed Bipolar Patients: 10-Year Outcomes in the Vitoria Prospective Naturalistic Study in Spain

OBJECTIVE There have been few prospective long-term naturalistic studies of patients with mixed episodes of bipolar disorder. The aim of this study was to examine 10-year outcomes in patients with at least 1 mixed episode. METHOD A naturalistic sample of bipolar I disorder patients (n = 120), representative of bipolar patients treated in a catchment area of Spain, was followed prospectively for up to 10 years. Outcomes including number (primary study outcome) and severity of episodes, hospitalizations, and suicide attempts were recorded at bimonthly visits. Bivariate and logistic regression models identified factors significantly associated with mixed episodes. The study was conducted from 1994 through 2004. RESULTS 37% of patients had mixed episodes. Mixed-episode patients had younger mean age at onset compared with the nonmixed group (25.3 vs 30.8 years; P = .025). After adjusting for age at onset, mixed-episode patients had an increased risk of hospitalization compared with the nonmixed group (OR = 2.86; 95% CI, 1.09-7.52; P = .033) and more episodes (OR = 1.21; 95% CI, 1.10-1.31; P < .001). Other differences between mixed and nonmixed patients, such as alcohol abuse, psychotic symptoms, and suicidality, were partially mediated by age at onset and were not significantly different after controlling for this variable. Mixed-episode patients with previous suicide attempts had a significantly shorter time to first suicide attempt during follow-up than those without history of suicide attempts (P = .014). CONCLUSIONS Although some factors associated with mixed episodes are mediated by a younger age at onset, the long-term prognosis of mixed-episode patients is worse than patients with nonmixed episodes.

Different profile of substance abuse in relation to predominant polarity in bipolar disorder: The Vitoria long-term follow-up study

BACKGROUND There is a need for comparisons of long-term outcomes in bipolar disorder patients with predominantly manic symptoms vs. predominantly depressive symptoms, especially the course of comorbid alcohol/substance abuse. METHOD A naturalistic sample of bipolar I patients (n=120) was followed prospectively for up to 10years. At baseline, number and polarity of past episodes were used to classify patients as predominantly manic or predominantly depressive if there were more manic or more depressive episodes, respectively. 25 patients were excluded from the analyses. Outcomes including episodes, hospitalisations and suicide attempts were recorded at bimonthly visits. Mixed effects models compared the course of alcohol and other substance abuse in predominantly manic vs. depressive patients. RESULTS Of the 95 patients analyzed, 44 (46.3%) had predominantly manic episodes and 51 (53.7%) had predominantly depressive episodes. At baseline, the predominantly depressive group had more history of suicide attempts (45.1% vs. 20.5%; p=0.021) and more family history of affective disorders (64.7% vs. 38.6%; p=0.020), but they had fewer previous hospitalisations than the manic group (mean 0.38 vs. 0.50; p=0.025). During the 10-year follow-up, the predominantly depressive group was associated with more episodes (p=0.001), more hospitalisations (p=0.004) and more suicide attempts (p=0.002). At baseline, there were no differences between the manic and depressive groups in the frequency of alcohol abuse (43.2% and 35.3%, p=0.565) or other substance abuse (13.6% and 9.8%, p=0.794). During the 10-year follow-up, the frequency of alcohol and other substance abuse decreased significantly in the manic group only, after controlling by age at onset and civil (marital) status. CONCLUSION Long-term clinical outcomes differ between predominantly manic vs. depressive bipolar patients, with the predominantly depressive group having a worse prognosis and maintained alcohol and other substance abuse. These differences should be considered when designing treatment approaches for bipolar patients with comorbid alcohol/substance abuse.

In-patient care costs of patients with bipolar I disorder: A comparison between two European centers

BACKGROUND Bipolar disorder (BPD) is a disabling disease with high morbidity rates. An international (Spain, France) comparative study about hospitalizations and in-patient care costs associated with BPD I was performed. Centers were included if they had access to a database of computerized patient charts exhaustively covering a defined catchment area. METHODS Economic evaluation was performed by multiplying the average cumulated annual length of stay (LOS) of hospitalized bipolar patients by a full cost per day of hospitalization in each center to obtain the corresponding annual costs. RESULTS Hospitalization rates per annum and per 100,000 individuals (general population aged 15+) were similar between France (43.6) and Spain (43.1). There were only slight differences in relation to length of stay (LOS) per patient hospitalized with 18.1 days in Spain and 20.4 days in France. The overall estimated annual hospitalization costs were in the same order of magnitude after adjustment to an adult population of 100,000: euro 232,000 (Spain) and euro 226,500 (France). Mixed episodes had the longest LOS followed by depressive episodes, while manic episodes had the shortest ones. Mania was the most costly disorder representing 53.7% of annual BPD in-patient care costs. CONCLUSIONS BPD I care requires large resources and frequent hospitalizations, especially during manic episodes. Depressive and mixed episodes require longer hospital stays than manic episodes. Out-patient costs should now be evaluated.

Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses

BACKGROUND The longitudinal neuropsychological study of first-episode early-onset psychosis (EOP) patients, whose brain maturation is still in progress at the time of illness onset, provides a unique opportunity to compare their cognitive development with that of healthy subjects, in search of specific patterns resulting from the interaction between neurodevelopmental processes and the presence of psychotic disorders. Method Seventy-five first-episode EOP patients (schizophrenia n = 35; bipolar disorder n = 17; other forms of psychosis n = 23) with a mean age of 15.53 years were assessed with a neuropsychological battery that included measures of attention, working memory, memory and executive functions within 6 months following the onset of the first psychotic symptom (baseline) and 2 years later. Psychotic symptoms were assessed at both times with the Positive and Negative Symptom Scale (PANSS). Seventy-nine healthy subjects matched for age and education served as controls. RESULTS EOP patients showed significant cognitive impairment at both baseline and the 2-year follow-up, with no significant differences between diagnostic groups at either time. Both healthy controls and EOP patients improved in all cognitive measures, except for patient working memory. Improvement in patient attention lost significance after controlling for psychotic symptom reduction. No significant time/diagnosis interaction was found among patients (p > 0.405). CONCLUSIONS Cognitive impairment in EOP is already present at the first episode, and cognitive development seems to be arrested early in EOP patients compared to their healthy peers, at least for some cognitive functions. These and previous similar results support the neurodevelopmental hypothesis of psychosis.

Plasma brain-derived neurotrophic factor levels, learning capacity and cognition in patients with first episode psychosis

BackgroundCognitive impairments are seen in first psychotic episode (FEP) patients. The neurobiological underpinnings that might underlie these changes remain unknown. The aim of this study is to investigate whether Brain Derived Neurotrophic Factor (BDNF) levels are associated with cognitive impairment in FEP patients compared with healthy controls.Methods45 FEP patients and 45 healthy controls matched by age, gender and educational level were selected from the Basque Country area of Spain. Plasma BDNF levels were assessed in healthy controls and in patients. A battery of cognitive tests was applied to both groups, with the patients being assessed at 6 months after the acute episode and only in those with a clinical response to treatment.ResultsPlasma BDNF levels were altered in patients compared with the control group. In FEP patients, we observed a positive association between BDNF levels at six months and five cognitive domains (learning ability, immediate and delayed memory, abstract thinking and processing speed) which persisted after controlling for medications prescribed, drug use, intelligence quotient (IQ) and negative symptoms. In the healthy control group, BDNF levels were not associated with cognitive test scores.ConclusionOur results suggest that BDNF is associated with the cognitive impairment seen after a FEP. Further investigations of the role of this neurotrophin in the symptoms associated with psychosis onset are warranted.

Validity and reliability of the Hamilton depression rating scale (5 items) for manic and mixed bipolar disorders.

Depressive symptoms during mania have prognostic value in bipolar disorder. For depressive symptoms, it has been proposed that shorter scales should be cost-effective and practical. To determine the usefulness of 5-item Hamilton Depression Rating Scale (HAMD-5) in manic and mixed bipolar disorder, we used a four-week follow-up prospective, observational study. Convergent and discriminant validity, internal consistency, and reliability were analyzed and compared with HAMD-21, HAMD-5, and HAMD-21 cut-off points were calculated versus CGI-BP. A total of 173 manic and mixed patients were evaluated. HAMD-5 showed appropriate convergent validity, discriminant validity, internal consistency, and test-retest reliability. Discriminant validity was higher for HAMD-5 than HAMD-21. Best cut-off point of remission was: HAMD-21 ≤5 and HAMD-5 ≤1. HAMD-5 presents appropriate validity and reliability estimates. It is comparable to HAMD-21 and focuses more specifically on depressive symptoms.

Validation and use of the functioning assessment short test in first psychotic episodes.

Numerous studies have documented high rates of functional impairment in patients with schizophrenia and bipolar disorder. However, this impairment appears early in the course of the illness. The purpose of the present study was to validate the Functioning Assessment Short Test (FAST) by comparing it with the Strauss-Carpenter Scale for use as an instrument to assess functional impairment in subjects with first psychotic episodes. The study was conducted on 53 patients admitted to Santiago Apostol Hospital because of a first psychotic episode. The FAST showed high internal consistency both at baseline and at 6 months as well as at 1 year. Concurrent validity showed a highly significant negative correlation at each time point. The FAST also showed good reliability and discriminant validity. The FAST showed strong psychometric properties and is a valid instrument for use in clinical practice, clinical trials, and research settings in subjects with first psychotic episodes.

Expression of oligodendrocyte and myelin genes is not altered in peripheral blood cells of patients with first-episode schizophrenia and bipolar disorder

Recent studies have reported oligodendrocyte and myelin abnormalities, as well as the dysregulation of their related genes, in the brains of patients with schizophrenia (SCZ) and bipolar disorder (BD) (1, 2), which suggest that white matter alterations contribute to the pathophysiology of these disorders. SCZ and BD are diseases for which no reliable biological test exists. Thus, it is necessary to find specific biomarkers. There is evidence pointing to a close integration between central nervous system and immunological functions, with lymphocytes playing a central role (3). Comparison of the peripheral blood transcriptome with genes expressed in the brain has revealed that more than 82% of the expressed genes were shared (4). Thus, peripheral blood may be an ideal surrogate tissue as it is readily obtainable and provides a large biosensor pool in the form of gene transcripts. Proof of the principle of this idea has been provided in a recent pioneer study combining whole-genome gene expression differences in blood samples from subjects with BD and changes in gene expression in brain and blood of a mouse pharmacogenomic model (5). Importantly, this study demonstrates that myelin ⁄oligodendrocyte genes are top blood candidate biomarkers of bipolar disease states in chronic patients (5). We have investigated here whether oligodendrocyte and myelin expression alterations in brain are detectable in peripheral blood cells (PBCs) from SCZ and BD patients. To achieve this objective, we examined messenger RNA (mRNA) levels of two major components of oligodendrocytes and myelin, 2¢,3¢-cyclic nucleotide 3¢-phosphodiesterase (CNPase) and myelin basic protein (MBP), in PBCs at the first psychotic episode in drug-naı̈ve patients and after one year of treatment. We recruited 59 patients (mean age ± SEM: 26.5 ± 1 year) from Vitoria (Spain) who experienced a first psychotic episode. Subjects with mental retardation, organic brain disorders, or drug abuse as a primary diagnosis were excluded. Total Positive and Negative Syndrome Scale (PANSS) (6) scores (mean ± SD) were 75.7 ± 23.0 at baseline and 53.5 ± 21.3 at 12 months. The Global Assessment of Functioning (GAF) score was 33.2 ± 10.7 at baseline and 56.8 ± 15.6 at 12 months. A total of 57.2% were smokers, 60.7% consumed alcohol, 12.5% abused alcohol, and 25% abused cannabis. Patients were diagnosed with SCZ (n = 39) or BD (n = 20) using the Structured Clinical Interview for DSM-IV (SCID-I). They were treated after the first episode with atypical antipsychotics (71.9%); lithium or other mood stabilizers together with atypical antipsychotics (22.3%); or typical antipsychotics (5.3%); or they received no treatment (3.5%). A total of 45 healthy volunteers were selected for this study from the same community and matched pairwise for sex and age (mean age ± SEM: 26.9 ± 1 year). The inclusion criteria for controls required the absence of any Axis I disorder, as well as the similar criteria that was applied to the patient group. Peripheral whole-blood samples were collected from patients upon arrival at the emergency room and again 12 months later, and from nonpsychiatric control subjects. Total RNA from PBCs was isolated and processed for real-time polymerase chain reaction (PCR) using primer pairs specific for MBP and CNPase and endogenous housekeeping genes as previously reported (7). Data are illustrated as the relative expression of each target gene normalized to housekeeping genes (7). Comparisons of normalized values between each patient group and controls were made between pairs matched for age and sex using two-tailed, unpaired Student s t-test. We did not find significant differences (all p > 0.5) in the relative expression of CNPase and MBP mRNAs in SCZ or in BD in the PBCs at Bipolar Disorders 2010: 12: 107–111 a 2010 The Authors Journal compilation a 2010 Blackwell Munksgaard