Patricia Vega

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.

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

The course of negative symptoms in first-episode schizophrenia and its predictors: A prospective two-year follow-up study

AIMS This study aimed to investigate the course of negative symptoms and its stability over a two-year period following a first-episode schizophrenia (FES) and the possible predictors of higher severity in this symptomatology after this period. METHODS In this longitudinal two-year prospective follow-up study we included 268 patients with a FES, according to DSM-IV. Analysis of variance was conducted in patients who completed the full follow-up to study changes in negative symptoms over three visits. Regression analyses were conducted to show correlates and potential predictors of negative symptoms at two-year follow-up. RESULTS There was a significant effect for time in negative symptomatology, which was less severe at one-year follow-up after a FES and remained stable up to two years (Time 1>Time 2>Time 3); F(2,151)=20.45, p<0.001. Poorer premorbid adjustment (p=0.01) and higher negative symptoms at baseline (p<0.001) made a significant contribution to the changes in the negative symptoms severity at two-years after a FES (R2=0.21, p<0.001). CONCLUSIONS We found a reduction in the negative symptomatology at one-year after a FES. This change remained stable at two-year. Our results suggested that the presence of this symptomatology early in the course of the illness, together with a poorer premorbid adjustment, predict more severe negative symptoms at mid-term outcome.

Manic and depressive symptoms and insight in first episode psychosis

Insight impairment is common early in the course of psychosis. Most studies have focused on the relationship between insight and depression, although manic symptoms are also frequent in psychoses. The main aim of this study was to examine the relationship between insight dimensions and manic and depressive symptoms in first-episode psychosis. A group of inpatients in their first psychotic episodes (n=124) were evaluated using the Scale to Assess Unawareness of Mental Disorder, Young Mania Rating Scale and Hamilton Depression Rating Scale. To study the effect of clinical, manic and depressive symptoms on insight, awareness of mental disorder, awareness of the achieved effects of medication, and awareness of the social consequences of having a mental disorder were modelled using ordinal logistic regression techniques. Results showed that greater awareness of mental disorder was significantly related to higher age at first episode together with higher scores for negative and depressive symptoms. The opposite was found to be true in presentations with a higher severity of disease and manic symptoms. The model fitting unawareness of the achieved effects of medication identified the same significant variables, except in the case of negative symptoms. Finally, the model assessing the social consequences of having a mental disorder showed unawareness to be greater when manic symptoms and disease severity were high.

Integrated treatment of first episode psychosis with online training (e-learning): study protocol for a randomised controlled trial

BackgroundThe integrated treatment of first episode psychosis has been shown to improve functionality and negative symptoms in previous studies. In this paper, we describe a study of integrated treatment (individual psychoeducation complementary to pharmacotherapy) versus treatment as usual, comparing results at baseline with those at 6-month re-assessment (at the end of the study) for these patients, and online training of professionals to provide this complementary treatment, with the following objectives: 1) to compare the efficacy of individual psychoeducation as add-on treatment versus treatment as usual in improving psychotic and mood symptoms; 2) to compare adherence to medication, functioning, insight, social response, quality of life, and brain-derived neurotrophic factor, between both groups; and 3) to analyse the efficacy of online training of psychotherapists.Methods/designThis is a single-blind randomised clinical trial including patients with first episode psychosis from hospitals across Spain, randomly assigned to either a control group with pharmacotherapy and regular sessions with their psychiatrist (treatment as usual) or an intervention group with integrated care including treatment as usual plus a psychoeducational intervention (14 sessions). Training for professionals involved at each participating centre was provided by the coordinating centre (University Hospital of Álava) through video conferences. Patients are evaluated with an extensive battery of tests assessing clinical and sociodemographic characteristics (Positive and Negative Syndrome Scale, State-Trait Anxiety Inventory, Liebowitz Social Anxiety Scale, Hamilton Rating Scale for Depression, Scale to Assess Unawareness of Mental Disorders, Strauss and Carpenter Prognostic Scale, Global Assessment of Functioning Scale, Morisky Green Adherence Scale, Functioning Assessment Short Test, World Health Organization Quality of Life instrument WHOQOL-BREF (an abbreviated version of the WHOQOL-100), and EuroQoL questionnaire), and brain-derived neurotrophic factor levels are measured in peripheral blood at baseline and at 6 months. The statistical analysis, including bivariate analysis, linear and logistic regression models, will be performed using SPSS.DiscussionThis is an innovative study that includes the assessment of an integrated intervention for patients with first episode psychosis provided by professionals who are trained online, potentially making it possible to offer the intervention to more patients.Trial registrationNCT01783457 clinical trials.gov. Date of registration in primary registry 23 January 2013.

Implicaciones clínicas de la edad de inicio del trastorno bipolar I: dos subgrupos con diferente pronóstico

INTRODUCTION AND OBJECTIVE Age at onset in bipolar disorder is related to prognosis and to treatment response. However, it is not clear if there are three or two subgroups in relation to age at onset. The objective of this study is to analyze the number of subgroups in relation to age at the beginning of the disease in a representative sample of bipolar I patients and to compare the subgroups in relation to clinical variables. METHOD We included 169 patients diagnosed with bipolar I disorder. Normal mixture analysis was performed. The subgroups of patients formed above were compared regarding clinical characteristics. Patients were followed-up during six years. RESULTS We found three ages at onset subgroups. The early onset group (18.2±2 years) included 34% of the patients. The second group (26.1±5.5 years) included 44% of the patients. The third group (50.9±9.1 years) included 22% of the patients. Early and intermediate onset groups were not significantly different, and had more family history of affective disorders, more psychotic symptoms, more history of suicide attempts and more history of drug abuse history than the late onset group. CONCLUSIONS Our results suggest that there are three groups of age at onset but early and intermediate groups are similar in relation to clinical variables. The late onset group includes almost a quartile of patients and has different clinical profile.