Fabiano Alves Gomes

Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia

UNLABELLED There is an increasing body of evidence suggesting that oxidative stress may play a role in the pathophysiology of both schizophrenia (SZ) and bipolar disorder (BD). METHODS We compared the antioxidant enzyme, serum superoxide dismutase (SOD) and the lipid peroxidation product, thiobarbituric acid reactive substances (TBARS) as assessed in depressed (N=21), manic (N=32) and euthymic (N=31) bipolar patients, and in chronically medicated patients with schizophrenia (N=97), all fulfilling DSM-IV diagnostic criteria, and a group of healthy controls (N=32). RESULTS Serum SOD (U/mg protein) activity was significantly increased (p<0.001) in manic (7.44+/-3.88) and depressed (6.12+/-4.64) BD patients and SZ (9.48+/-4.51) when compared to either controls (1.81+/-0.63) or euthymic (2.75+/-1.09) BD patients. TBARS (mol/L) levels were significantly higher in the SZ group (4.95+/-1.56, p=0.016), bipolar euthymic (6.36+/-1.46, p<0.001), bipolar manic (7.54+/-1.74, p<0.001), and bipolar depressed patients (5.28+/-1.54, p=0.028) compared to controls (3.96+/-1.51). DISCUSSION Our findings show increased SOD activity in SZ, as well as in depressed and manic bipolar patients, but not in euthymic BD subjects. This suggests a dysregulation in oxidative defenses in both disorders. It is likely that such changes reflect state changes in bipolar disorder. It is possible that this is a compensatory response to the oxidative stress that occurs in the acute phase of bipolar episodes. TBARS results show increases in lipid peroxidation in mania. TBARS levels in SZ and in euthymic as well as depressed individuals with BD were higher than in controls. This suggests persistent increases in SZ, which may reflect ongoing symptomatology or treatment, and a state dependent gradient in BD, with greatest oxidative stress in mania. These data support oxidative biology as both a key component of the pathophysiology of both BD and SZ, and the use of agents that modulate oxidative biology as a promising avenue for intervention in both disorders.

Increased oxidative stress and DNA damage in bipolar disorder: A twin-case report

OBJECTIVE There is an emerging body of data suggesting that oxidative stress may be associated with the pathophysiology of bipolar disorder (BD). In the present study we investigated the oxidative stress profile in two monozygotic twins during a manic episode. METHODS Two monozygotic twins diagnosed as currently manic by the Structured Clinical Interview for DSM-IV were studied. Serum thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and catalase (CAT) were measured as parameters of oxidative stress. DNA damage was assessed using the single cell gel electrophoresis technique (Comet Assay). All biochemical measures were conducted at baseline and after a 6-week treatment. RESULTS Bipolar twins had higher TBARS, SOD and DNA damage, and lower CAT than the healthy control. TBARS and SOD were normalized after mood stabilization, whereas CAT and DNA damage remained altered at week 6. CONCLUSIONS These findings support that oxidative stress may play a role in the pathophysiology of BD and that pharmacological treatment may exert antioxidant effects. Studies with larger samples are warranted to further clarify this issue.

Investigation of serum high-sensitive C-reactive protein levels across all mood states in bipolar disorder

There has been an increasing interest in the role of the immune and inflammatory systems in mood disorders. Mood episodes are associated with changes in acute phase proteins such as high-sensitivity C-reactive protein (hsCRP). The present study investigated serum hsCRP in manic, depressed, and euthymic BD patients as compared to matched healthy controls. Serum hsCRP was assessed using an ultrasensitive assay of particle-enhanced immunoturbidimetric latex agglutination. Serum hsCRP levels were increased in manic BD patients, as compared to euthymic, depressed patients and healthy controls (P < 0.001). These findings add to the notion that changes in the inflammatory system take place during acute episodes of mania.

Improvement of Negative and Positive Symptoms in Treatment-Refractory Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Trial With Memantine as Add-On Therapy to Clozapine

BACKGROUND Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate (NMDA) receptor dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimers disease, acts as a weak nonselective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia. METHOD In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according to DSM-IV clinical criteria were randomly assigned, from March 2005 to February 2008, to receive either 20 mg/d memantine (n = 10) or placebo (n = 11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale (BPRS) and BPRS subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale (CGI), cognition as assessed by the Mini-Mental State Examination (MMSE), and extrapyramidal symptoms as assessed by the Simpson-Angus Scale (SAS). RESULTS Twenty-one participants completed the study and were used in the analysis. Significant improvement (P < .01) on the total BPRS score, its subscales of positive (effect size [ES] = -1.38) and negative (ES = -3.33) symptoms, the CGI score (ES = 1.56), and the MMSE score was observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed. CONCLUSIONS Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00757978.

Obesity is associated with previous suicide attempts in bipolar disorder

Gomes FA, Kauer-Sant’Anna M, Magalhães PV, Jacka FN, Dodd S, Gama CS, Cunha Â, Berk M, Kapczinski F. Obesity is associated with previous suicide attempts in bipolar disorder. Objective: There is a paucity of data about risk factors for suicide attempts in bipolar disorder. The aim of this study is to examine the association between suicide attempts and obesity in people with bipolar disorder. Methods: Two hundred fifty-five DSM-IV out-patients with bipolar disorder were consecutively recruited from the Bipolar Disorder Program at Hospital das Clínicas de Porto Alegre and the University Hospital at the Universidade Federal de Santa Maria, Brazil. Diagnosis and clinical variables were assessed with Structured Clinical Interview for DSM-IV-axis I (SCID I) and Program structured protocol. History of suicide attempts was obtained from multiple information sources including patients, relatives and review of medical records. Patients with body mass index (BMI) ≥ 30 were classified as obese. Results: Over 30% of the sample was obese and over 50% had a history of suicide attempt. In the multivariate model, obese patients were nearly twice (OR = 1.97, 95% CI: 1.06–3.69, p = 0.03) as likely to have a history of suicide attempt(s). Conclusion: Our results emphasise the relevance of obesity as an associated factor of suicide attempts in bipolar disorder. Obesity may be seen as correlate of severity and as such, must be considered in the comprehensive management of bipolar patients.

Cardiovascular risk factors in outpatients with bipolar disorder: a report from the Brazilian Research Network in Bipolar Disorder

OBJECTIVE Bipolar disorder (BD) is associated with significant morbidity and mortality due to comorbid general medical conditions, particularly cardiovascular disease. This study is the first report of the Brazilian Research Network in Bipolar Disorder (BRN-BD) that aims to evaluate the prevalence and clinical correlates of cardiovascular risk factors among Brazilian patients with BD. METHODS A cross-sectional study of 159 patients with DSM-IV BD, 18 years or older, consecutively recruited from the Bipolar Research Program (PROMAN) in São Paulo and the Bipolar Disorder Program (PROTAHBI) in Porto Alegre. Clinical, demographic, anthropometric, and metabolic variables were systematically assessed. RESULTS High rates of smoking (27%), physical inactivity (64.9%), alcohol use disorders (20.8%), elevated fasting glucose (26.4%), diabetes (13.2%), hypertension (38.4%), hypertriglyceridemia (25.8%), low HDL-cholesterol (27.7%), general (38.4%) and abdominal obesity (59.1%) were found in the sample. Male patients were more likely to have alcohol use disorders, diabetes, and hypertriglyceridemia, whereas female patients showed higher prevalence of abdominal obesity. Variables such as medication use pattern, alcohol use disorder, and physical activity were associated with selected cardiovascular risk factors in the multivariable analysis. CONCLUSION This report of the BRN-BD provides new data regarding prevalence rates and associated cardiovascular risk factors in Brazilian outpatients with BD. There is a need for increasing both awareness and recognition about metabolic and cardiovascular diseases in this patient population.

Birth-cohort and dual diagnosis effects on age-at-onset in Brazilian patients with bipolar I disorder.

Objective:  Substance use disorders and birth‐cohort have been associated with an earlier onset in bipolar disorder (BD). This study aimed at evaluating the inter‐relations of these factors in age‐at‐onset in bipolar illness.

Serum levels of brain-derived neurotrophic factor in acute and posttraumatic stress disorder: a case report study

OBJECTIVE The aim of this study was to evaluate brain-derived neurotrophic factor levels in two patients, one with posttraumatic stress disorder and one with acute stress disorder, before and after treatment, and to compare those levels to those of healthy controls. METHOD Brain-derived neurotrophic factor level, Davidson Trauma Scale, Beck Depression Inventory, Global Assessment of Functioning, and Clinical Global Impression were assessed before and after 6 weeks of treatment. RESULTS Brain-derived neurotrophic factor levels were higher in patients than in matched controls before treatment. After 6 weeks, there was a reduction in symptoms and an improvement in functioning in both cases. At the same time, brain-derived neurotrophic factor levels decreased after treatment, even in case 2, treated with psychotherapy only. CONCLUSIONS These results suggest that serum levels of brain-derived neurotrophic factor, as opposed to what has been described in mood disorders, are increased in posttraumatic stress disorder as well as in acute stress disorder.

Resistência à insulina e síndrome metabólica em pacientes ambulatoriais com transtorno do humor bipolar

Background: Bipolar disorder (BD) is associated with significant morbidity and mortality from metabolic diseases. There is a paucity of data regarding insulin resistance (IR) and its relationship with the metabolic syndrome (MS) in bipolar patients. Objective: To evaluate the prevalence of both IR and MS in BD outpatients and to assess clinical criteria associated with IR. Method: Cross-sectional study in 65 DSM-IV-TR BD patients consecutively assessed at the Bipolar Disorder Program at Hospital de Clinicas de Porto Alegre, Brazil. IR was diagnosed by the homeostatic model assessment – insulin resistance (HOMA-IR) and MS was diagnosed using three different definitions: National Cholesterol Educational Program – Adult Treatment Panel III (NCEP-ATP III); NCEP-ATP III modified criteria and International Diabetes Federation. Results: IR was present in 43.1% of the sample (women 40%, men 44.4%). The prevalence of MS defined by the NCEP-ATP III criteria was 32.3%, NCEP-ATP III modified was 40% and IDF was 41.5%. NCEP-ATP III modified criteria showed the best tradeoff between sensitivity (78.6%) and specificity (89.2%) to detect insulin resistance. Waist circumference was the clinical parameter most associated with IR. Discussion: Current MS criteria may provide reasonable sensitivity and specificity for the detection of IR in BD patients. Abdominal obesity is closely related to IR in this patient population.

Validity of the Portuguese version of the Bipolar Depression Rating Scale

Depressive episodes may have clinical features in people with bipolar disorder (BD) that are distinct from unipolar depression (1,2). Concomitant (hypo) manic symptoms are frequently unnoticed, especially when they do not reach the threshold of Diagnostic Statistical Manual -IV (DSM-IV) mixed episodes (3,4). Generic depression scales fail to capture unique phenomenological aspects of bipolar depression, particularly atypical symptoms and mixed states, making their use problematic (5). Combining measures of depression and mania is one alternative that may mitigate