Fabiana Nery-Fernandes

Is cerebellar volume related to bipolar disorder

BACKGROUND Recent data suggest that cerebellum influences emotion modulation in humans. The findings of cerebellar abnormalities in bipolar disorder (BD) are especially intriguing given the link between the cerebellum emotional and behavioral regulation. The purpose of this study was to evaluate cerebellar volume in patients with euthymic BD type I compared to controls. Moreover, we investigated the possible relationship between cerebellar volume and suicidal behavior. METHODS Forty-patients with euthymic BD type I, 20 with and 20 without history of suicide attempt, and 22 healthy controls underwent an MRI scan. The participants were interviewed using the Structured Clinical Interview with the DSM-IV axis I (SCID-I), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS) and the Barratt Impulsiveness Scale (BIS-11). RESULTS Groups were age, gender and years of schooling-matched. The left cerebellum (p=0.02), right cerebellum (p=0.02) and vermis (p<0.01) were significantly smaller in the BD group; however, there were no volumetric differences between the BD subjects with and without suicidal attempt. There was no correlation between cerebellar measurements and clinical variables. LIMITATIONS The main strength is that our sample consisted of patients with euthymic BD type I without any comorbidities, however, these results cannot establish causality as the cross-sectional nature of the study. CONCLUSIONS Our findings suggest that the reduction in cerebellar volumes observed in BD type I might be a trait-related characteristic of this disorder. Additional studies with larger samples and subtypes of this heterogeneous disorder are warranted to determine the possible specificity of this cerebellar finding.

The impact of comorbid posttraumatic stress disorder on bipolar disorder patients

BACKGROUND Available data regarding posttraumatic stress disorder (PTSD) in bipolar disorder (BD) are scarce and usually from a limited sample size. The present report was carried out using the Brazilian Research Consortium for Bipolar Disorders and aimed to examine whether patients with BD and comorbid PTSD are at an increased risk for worse clinical outcomes. METHODS A consecutive sample of bipolar I outpatients from two teaching hospitals in Brazil was recruited. Patients were assessed using the Structured Clinical Interview for DSM-IV, Young Mania Rating Scale, 17-item Hamilton Rating Scale for Depression, and quality of life instrument WHOQOL-BREF. Participants were divided into three groups: a. bipolar patients with PTSD, b. bipolar patients exposed to trauma without PTSD, and c. bipolar patients with no trauma exposure. RESULTS Of the 405 patients who consented to participate, 87.7% completed the survey. All three groups were similar in terms of demographic parameters. The group with comorbid PTSD reported worse quality of life, more rapid cycling, higher rates of suicide attempts, and a lower likelihood of staying recovered. LIMITATIONS The cross-sectional design excludes the opportunity to examine causal relationships among trauma, PTSD, and BD. CONCLUSIONS The findings indicate that PTSD causes bipolar patients to have a worse outcome, as assessed by their lower likelihood to recover, elevated proportion of rapid cycling periods, increased risk of suicide attempts, and worse quality of life.

Reduced posterior corpus callosum area in suicidal and non-suicidal patients with bipolar disorder

BACKGROUND Impulsivity is a characteristic of bipolar disorder (BD) that can contribute to the risk for suicidal behavior. Evidence suggests that gray and white matter abnormalities are linked with impulsivity, but little is known about the association between corpus callosum (CC) and impulsivity in BD. We examined the CC area and impulsivity in euthymic bipolar I patients, with and without lifetime history of suicide attempts, and in healthy controls. METHODS Nineteen bipolar patients with a suicide attempt history (BP-S), 21 bipolar patients without suicide attempt history (BP-NS), and 22 healthy controls (HC) underwent clinical assessment by the Structured Clinical Interview with the DSM-IV axis I (SCID-I), the Barratt Impulsiveness Scale (BIS-11), and MRI scan. RESULTS No differences were observed for any CC subregion between BP-S and BP-NS groups. There was a significant reduction in the genu (p=0.04) and isthmus areas (p=0.01), in bipolar patients compared with HC. In the BP-S group, the BIS-11 total (p=0.01), attention (p=0.001) and non-planning (p=0.02) impulsivity scores were significantly higher than in the BP-NS and HC groups. LIMITATIONS These results cannot establish causality because of the cross-sectional nature of the study. CONCLUSION This report potentially provides evidence that a reduction in the CC area is present even in non-symptomatic bipolar patients, which may be evidence of a biological trait marker for BD. Furthermore, the study demonstrated that BP-S group had higher impulsivity even during euthymia, which points to a sustained association between lifetime history of suicide attempts and impulsivity in BD.

Is there an association between suicide attempt and delay of initiation of mood stabilizers in bipolar I disorder

BACKGROUND Little is known about the extent to which delay of initiation of mood-stabilizing treatment may influence outcomes in bipolar patients (BP). In this study, our aim was to investigate the association between delay of mood stabilizer treatment in bipolar patients and lifetime history of suicide attempts. METHOD A consecutive sample of 268 bipolar I outpatients from two teaching hospitals in Brazil was recruited. The assessment included a socio-demographic history form, a clinical interview regarding clinical variables and the Structured Clinical Interview for DSM-IV. Participants were divided into three groups: BP that initiated the first mood stabilizer in the same year of the first episode of the disease (FMS≤1), between 1 and 5 years after the first episode of the disease (15). RESULTS The mean time from the first episode until the first mood stabilizer medication was 8.6 years (SD 9.8 years). The FMS>5 group, showed a higher lifetime prevalence of suicide attempts than the other two groups (PR=1.75, 95% CI: 1.24-2.47), p=0.001. These results remained significant after adjusting for potential confounders, (PR=1.82, 95% CI: 1.29-2.60), p=0.001. LIMITATIONS This study evaluated patients retrospectively and does not permit a cause-effect relationship. CONCLUSION The present study supports the importance of early diagnosis and early intervention for BP in order to limit the potentially lethal impact of the disease.

Prevalence and clinical correlates of alcohol use disorders among bipolar disorder patients: results from the Brazilian Bipolar Research Network.

OBJECTIVES To investigate prevalence rates and clinical correlates of alcohol use disorders (AUD) among bipolar disorder (BD) patients in a large sample from the Brazilian Bipolar Research Network. METHODS Four hundred and eighty-three DSM-IV BD patients, divided according to the presence or absence of a lifetime AUD diagnosis (BD-AUD vs. BD-nonAUD), were included. Demographic and clinical characteristics of these two groups were compared. Logistic regression was performed to identify which characteristics were most strongly associated with a lifetime AUD diagnosis. RESULTS Nearly 23% presented a lifetime AUD diagnosis. BD-AUD patients were more likely to be male, to present rapid cycling, post-traumatic stress disorder (PTSD), anorexia, other substance use disorders (SUD), family history of SUD, any substance misuse during the first mood episode, history of psychosis, suicide attempts, and younger age at onset of illness than BD-nonAUD patients. Logistic regression showed that the variables most strongly associated with a lifetime AUD diagnosis were SUD (non-alcohol), any substance misuse during the first mood episode, PTSD, male gender, suicide attempt, family history of SUD, and younger age at onset of BD. CONCLUSIONS BD-AUD patients begin their mood disorder earlier and present more suicidal behaviors than BD-nonAUD patients. Personal and family history of SUD may be good predictors of comorbid AUD among BD patients. These variables are easily assessed in the clinical setting and may help to identify a particularly severe subgroup of BD patients.

Lower rates of comorbidities in euthymic bipolar patients.

Objective. This study assessed the frequency of axis I psychiatric comorbidities in euthymic bipolar patients and the clinical differences between patients with and without comorbidities. Method. In this study, 62 euthymic bipolar outpatients assessed using a clinical questionnaire underwent a structured diagnostic interview (SCID/CV – DSM-IV) as well as a symptoms evaluation (YMRS and HAM-D-17). Results. The lifetime frequency of patients with comorbidities was 27.4%. The most frequent comorbidities were anxiety disorders (33.7%), and the positive associated variables were more advanced age, the presence of a steady partner, a first episode of the depressive type and lifetime attempted suicide. Conclusions. The lower frequency of comorbidities found in our study in comparison with those described in the literature may be due to the evaluation restricted only to euthymic patients. This suggests the importance of assessing psychiatric comorbidity in bipolar individuals while not in acute phases of the disorder.

Prevalence and clinical impact of eating disorders in bipolar patients

OBJECTIVES To study the impact of eating disorders (EDs) on the severity of bipolar disorder (BD). METHODS The Structured Clinical Interview for DSM-IV Axis I (SCID-I), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D-17), Hamilton Anxiety Rating Scale (HAM-A), Global Assessment of Functioning (GAF), Clinical Global Impression (CGI), and the World Health Organization Quality of Life Assessment (WHOQOL-BREF) were used. Clinical and sociodemographic data were also collected. RESULTS Among the 356 bipolar patients included in this study, 19 (5.3%) were also diagnosed with ED. Of these, 57.9% had bulimia nervosa (BN) and 42.1% had anorexia nervosa (AN). Among ED patients, 94.7% were female. Bipolar patients with EDs presented with lower scores in the mental health domain of the WHOQOL-BREF, higher scores of depressive symptoms, and more psychiatric comorbidities. CONCLUSIONS ED comorbidities imposed important negative outcomes in bipolar patients. This finding suggests that attention should be given to the presence of EDs in BD patients and that better treatments focused on this population should be developed.

The identification of unipolar mania subtype based on anxiety comorbidity

BACKGROUND Unipolar mania is a controversial topic. Clinical research has focused on establishing specific characteristics that allow it to be distinguished from bipolar disorder (BD). METHODS Experienced and carefully trained clinicians evaluated a clinical sample of 298 patients with bipolar disorder using structured instruments to analyze the clinical and socio-demographics differences between people with manic episodes over the course of a 15-year illness compared with participants with histories of manic and depressive episodes. RESULTS According to adopted criteria, 16 (5.6%) participants presented unipolar mania (UM) and 282 participants presented manic and depressive (MD) phases. UM patients reported significantly more hospitalizations and medications, as well as more frequent psychosis at the first episode in the UM group than compared to the MD group. The UM group showed worse overall functioning, although differences in mood status between groups were not identified. Comorbid anxiety disorders and anxiety symptoms occurred significantly less frequently in the UM group. LIMITATIONS Because of the cross-sectional design, determining causal relationships was not possible. Furthermore, the retrospective nature of the UM diagnosis could not exclude a future depressive episode. CONCLUSIONS The presence of anxiety disorders can differentiate patients with unipolar mania from those with bipolar mania.

The impacts of cognitive-behavioral therapy on the treatment of phobic disorders measured by functional neuroimaging techniques: a systematic review

OBJECTIVE Functional neuroimaging techniques represent fundamental tools in the context of translational research integrating neurobiology, psychopathology, neuropsychology, and therapeutics. In addition, cognitive-behavioral therapy (CBT) has proven its efficacy in the treatment of anxiety disorders and may be useful in phobias. The literature has shown that feelings and behaviors are mediated by specific brain circuits, and changes in patterns of interaction should be associated with cerebral alterations. Based on these concepts, a systematic review was conducted aiming to evaluate the impact of CBT on phobic disorders measured by functional neuroimaging techniques. METHODS A systematic review of the literature was conducted including studies published between January 1980 and April 2012. Studies written in English, Spanish or Portuguese evaluating changes in the pattern of functional neuroimaging before and after CBT in patients with phobic disorders were included. RESULTS The initial search strategy retrieved 45 studies. Six of these studies met all inclusion criteria. Significant deactivations in the amygdala, insula, thalamus and hippocampus, as well as activation of the medial orbitofrontal cortex, were observed after CBT in phobic patients when compared with controls. CONCLUSION In spite of their technical limitations, neuroimaging techniques provide neurobiological support for the efficacy of CBT in the treatment of phobic disorders. Further studies are needed to confirm this conclusion.

Normal Metabolic Levels in Prefrontal Cortex in Euthymic Bipolar I Patients with and without Suicide Attempts

Introduction/Objective. Evidence suggests that the prefrontal cortex has been implicated in the pathophysiology of bipolar disorder (BD), but few neurochemical studies have evaluated this region in bipolar patients and there is no information from BD suicide attempters using Proton Magnetic Resonance Spectroscopy (H+MRS). The objective was to evaluate the metabolic function of the medial orbital frontal cortex in euthymic BD type I suicide and nonsuicide attempters compared to healthy subjects by H+MRS. Methods. 40 euthymic bipolar I outpatients, 19 without and 21 with history of suicide attempt, and 22 healthy subjects were interviewed using the Structured Clinical Interview with the DSM-IV axis I, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Barratt Impulsiveness Scale-11 and underwent H+MRS. Results. We did not find any metabolic abnormality in medial orbital frontal regions of suicide and nonsuicide BD patients and BD patients as a group compared to healthy subjects. Conclusions. The combined chronic use of psychotropic drugs with neuroprotective or neurotrophic effects leading to a euthymic state for longer periods of time may improve neurometabolic function, at least measured by H+MRS, even in suicide attempters. Besides, these results may implicate mood dependent alterations in brain metabolic activity. However, more studies with larger sample sizes of this heterogeneous disorder are warranted to clarify these data.