Leonardo Evangelista da Silveira

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.

Cognitive change in the year after a first manic episode: association between clinical outcome and cognitive performance early in the course of bipolar I disorder.

OBJECTIVE Cognitive impairments are present immediately following recovery from a first episode of mania, although at a lesser severity than those seen in more chronic patients with bipolar I disorder. Little is known about how deficits evolve over the course of illness, however, and whether these changes are associated with disease progression. METHOD Patients with bipolar I disorder (DSM-IV-TR) receiving naturalistic clinical follow-up from the Systematic Treatment Optimization Program for Early Mania (STOP-EM) from July 2004 to May 2013 completed a comprehensive cognitive battery following recovery from their first manic episode and again 1 year later. Performance was compared between patients who experienced a recurrence of a mood episode (BDrecur) (n = 26) versus those that maintained remission (BDwell) (n = 27) over follow-up, as well as healthy comparison subjects (HS) (n = 31). RESULTS While both BDrecur and BDwell had impairments in overall cognitive performance relative to HS at baseline (mean difference = -0.59, P < .001; mean difference = -0.43, P < .05, respectively), at follow-up BDrecur showed deficits compared to both HS (mean difference = -0.62, P = .001) and BDwell (mean difference = -0.41, P = .05), with BDwell cognition similar to that in HS (mean difference = -0.21, P > .4). BDwell showed larger improvements over follow-up relative to both other groups (P < .05). While changes in BDrecur did not differ from HS, in this group more days in a manic or hypomanic episode was associated with performance declines (r = -0.40, P < .05). CONCLUSIONS While cognitive function improves in patients who sustain remission in the year following a first manic episode, those who experience a recurrence remain impaired, with performance declines being most apparent in those who experienced longer manic or hypomanic episodes.

Effects of a single bout of maximal aerobic exercise on BDNF in bipolar disorder: A gender-based response

Acute exercise increases brain-derived neurotrophic factor (BDNF) serum levels in majorly depressed and anxious patients. However, to the best of our knowledge, no study has evaluated the acute effects of exercise on BDNF serum levels in Bipolar Disorder (BD). The objective of the present study was to evaluate the peripheral BDNF serum response to a single maximum session of exercise in BD participants and age- and gender-matched healthy participants. BD participants (n=18) and age- and gender-matched healthy participants (n=18) were recruited to perform a single bout of maximal exercise on a cycle ergometer. Blood samples were collected prior to and immediately after the exercise protocol. There was a significant group effect and a significant group x time x gender interaction. BD participants presented significantly higher BDNF serum levels when compared to their healthy control counterparts. Exercise increases the BDNF levels of BD women, but not men.

Are cognitive deficits similar in remitted early bipolar I disorder patients treated with lithium or valproate? Data from the STOP-EM study

In bipolar disorder (BD), lithium and valproate are both reportedly associated with mild cognitive deficits with impaired psychomotor speed and verbal memory ascribed to both while impairments in learning and attention are mainly attributed to valproate. However, there are few direct comparisons of the impact of lithium and valproate on cognitive function in early BD. Using data from the STOP-EM study, we compared neurocognitive functioning in BD patients, who had recently recovered from a first episode of mania, and were on treatment with lithium (n = 34) or valproate (n = 38), to a comparable sample of healthy controls (HC; n = 40), on the domains of processing speed, attention, verbal memory, nonverbal memory, working memory and executive functions. The three groups were comparable on socio-demographic (all p > 0.12) and clinical variables (all p > 0.08). MANOVA revealed a significant difference between the three groups on overall cognitive functioning (Wilks lambda = 0.644; F = 3.775; p < 0.001). On post-hoc Tukey test, the valproate group performed poorer on working memory compared to the lithium (p = 0.001) and HC groups (p < 0.001). There was no significant difference between the lithium and valproate groups on other cognitive domains (all p > 0.13). Treatment with valproate and not lithium may be associated with working memory deficits early in the course of BD.

The impact of childhood trauma on cognitive functioning in patients recently recovered from a first manic episode: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

BACKGROUND Both bipolar disorder (BD) and childhood trauma are associated with cognitive impairment. People with BD have high rates of childhood trauma, which confer greater overall disease severity, but, it is unknown if childhood trauma is associated with greater neurocognitive impairment in BD patients early in the course of their illnesses. In this study, we investigated the impact of childhood trauma on specific cognitive dysfunction in patients who recently recovered from their first episode of mania. METHODS Data were available for 64 patients and 28 healthy subjects matched by age, gender and pre-morbid IQ, recruited from a large university medical center. History of childhood trauma was measured using the Childhood Trauma Questionnaire. Cognitive function was assessed through a comprehensive neuropsychological test battery. RESULTS Trauma was associated with poorer cognitive performance in patients on cognitive measures of IQ, auditory attention and verbal and working memory, and a different pattern was observed in healthy subjects. LIMITATIONS We had a modest sample size, particularly in the group of healthy subjects with trauma. CONCLUSIONS Childhood trauma was associated with poorer cognition in BD patients who recently recovered from a first episode of mania compared to healthy subjects. The results require replication, but suggest that the co-occurrence of trauma and bipolar disorder can affect those cognitive areas that are already more susceptible in patients with BD.

Neurocognitive functioning in overweight and obese patients with bipolar disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

Objective: Obesity is frequent in people with bipolar I disorder (BD I) and has a major impact on the course of the illness. Although obesity negatively influences cognitive function in patients with BD, its impact in the early phase of the disorder is unknown. We investigated the impact of overweight and obesity on cognitive functioning in clinically stable patients with BD recently recovered from their first manic episode. Method: Sixty-five patients with BD (25 overweight or obese and 40 normal weight) recently remitted from a first episode of mania and 37 age- and sex-matched healthy control subjects (9 overweight or obese and 28 normal weight) were included in this analysis from the Systematic Treatment Optimization Program for Early Mania (commonly referred to as STOP-EM). All subjects had their cognitive function assessed using a standard neurocognitive battery. We compared cognitive function between normal weight patients, overweight-obese patients, and normal weight healthy control subjects. Results: There was a negative affect of BD diagnosis on the domains of attention, verbal memory, nonverbal memory, working memory, and executive function, but we were unable to find an additional effect of weight on cognitive functioning in patients. There was a trend for a negative correlation between body mass index and nonverbal memory in the patient group. Conclusions: These data suggest that overweight-obesity does not negatively influence cognitive function early in the course of BD. Given that there is evidence for a negative impact of obesity later in the course of illness, there may be an opportunity to address obesity early in the course of BD.

Childhood maltreatment and corpus callosum volume in recently diagnosed patients with bipolar I disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

Childhood trauma (CT) has been associated with abnormalities in the corpus callosum (CC). Decreased CC volumes have been reported in children and adolescents with trauma as well as adults with CT compared to healthy controls. CC morphology is potentially susceptible to the effects of Bipolar Disorder (BD) itself. Therefore, we evaluated the relationship between CT and CC morphology in BD. We using magnetic resonance imaging in 53 adults with BD recently recovered from their first manic episode, with (n = 23) and without (n = 30) CT, defined using the Childhood Trauma Questionnaire (CTQ) and 16 healthy controls without trauma. ANCOVA was performed with age, gender and intracranial volume as covariates in order to evaluate group differences in CC volume. The total CC volume was found to be smaller in BD patients with trauma compared to BD patients without trauma (p < .05). The differences were more pronounced in the anterior region of the CC. There was a significant negative correlation between CTQ scores and total CC volume in BD patients with trauma (p = .01). We did not find significant differences in the CC volume of patients with/without trauma compared to the healthy subjects. Our sample consists of patients recovered from a first episode of mania and are early in the course of illness and reductions in CC volume may occur late in the course of BD. It might mean there may be two sources of CC volume reduction in these patients: the reduction due to trauma, and the further reduction due to the illness.

Impact of depressive episodes on cognitive deficits in early bipolar disorder: data from the Systematic Treatment Optimization Programme for Early Mania (STOP-EM)

BACKGROUND Although manic episodes reportedly contribute to cognitive deficits in bipolar I disorder, the contribution of depressive episodes is poorly researched. AIMS We investigated the impact of depressive episodes on cognitive function early in the course of bipolar I disorder. METHOD A total of 68 patients and 38 controls from the Systematic Treatment Optimization Programme for Early Mania (STOP-EM) first-episode mania programme were examined. We conducted (a) a cross-sectional analysis of the impact of prior depressive episodes on baseline cognitive function and (b) a prospective analysis assessing the contribution of depression recurrence within 1 year following a first episode of mania on cognitive functioning. RESULTS The cross-sectional analysis showed no significant differences between patients with past depressive episodes compared with those without, on overall or individual domains of cognitive function (all P>0.09). The prospective analysis failed to reveal a significant group×time interaction for cognitive decline from baseline to 1 year (P = 0.99) in patients with a recurrence of depressive episodes compared with those with no recurrence. However, impaired verbal memory at baseline was associated with a depression recurrence within 1 year. CONCLUSIONS Although deficits in all domains of cognitive function are seen in patients early in the course of bipolar disorder, depressive episodes do not confer additional burden on cognitive function. However, poorer verbal memory may serve as a marker for increased susceptibility to depression recurrence early in the course of illness.

Effectiveness of Pulmonary Rehabilitation in Exercise Capacity and Quality of Life in Chronic Obstructive Pulmonary Disease Patients With and Without Global Fat-Free Mass Depletion

OBJECTIVE To investigate the effectiveness of pulmonary rehabilitation (PR) in exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD) with and without global fat-free mass (FFM) depletion. DESIGN Retrospective case-control. SETTING Outpatient clinic, university center. PARTICIPANTS COPD patients (N=102) that completed PR were initially evaluated. INTERVENTION PR including whole-body and weight training for 12 weeks, 3 times per week. MAIN OUTCOME MEASURES St. George Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), and FFM evaluation applied before and after PR. RESULTS Patients were stratified according to their FFM status measured by bioelectric impedance. They were considered depleted if the FFM index was ≤ 15 kg/m(2) in women and ≤ 16 kg/m(2) in men. From the initial sample, all depleted patients (n=31) composed the FFM depleted group. It was composed predominantly by women (68%) with a mean age ± SD of 64.4 ± 7.3 years and a forced expiratory volume in 1 second of 33.6%=-13.2% predicted. Paired for sex and age, 31 nondepleted patients were selected from the initial sample to compose the nondepleted group. Improvement in the 6MWD was similar in these 2 groups after PR. Both groups improved SGRQ scores, although the observed power was small and did not allow adequate comparison between depleted and nondepleted patients. There was no difference between groups in weight change, whereas FFM tended to be greater in depleted patients. This increase had no correlation with the 6MWD or the SGRQ. CONCLUSIONS Benefits of PR to exercise capacity were similar comparing FFM depleted and nondepleted COPD patients. Although FFM change tended to be greater in depleted patients, this increase had no definite relation with clinical outcomes.

Relationship between body mass index and hippocampal glutamate/glutamine in bipolar disorder

BACKGROUND We previously reported that patients with early-stage bipolar disorder, but not healthy comparison controls, had body mass index (BMI)-related volume reductions in limbic brain areas, suggesting that the structural brain changes characteristic of bipolar disorder were more pronounced with increased weight. AIMS To determine whether the most consistently reported neurochemical abnormality in bipolar disorder, increased glutamate/glutamine (Glx), was also more prominent with higher BMI. METHOD We used single-voxel proton magnetic resonance spectroscopy to measure hippocampal Glx in 51 patients with first-episode mania (mean BMI = 24.1) and 28 healthy controls (mean BMI = 23.3). RESULTS In patients, but not healthy controls, linear regression demonstrated that higher BMI predicted greater Glx. Factorial ANCOVA showed a significant BMI × diagnosis interaction, confirming a distinct effect of weight on Glx in patients. CONCLUSIONS Together with our volumetric studies, these results suggest that higher BMI is associated with more pronounced structural and neurochemical limbic brain changes in bipolar disorder, even in early-stage patients with low obesity rates.