José Antônio Amaral

Clinical expression of obsessive-compulsive disorder in women with bipolar disorder.

OBJECTIVE To study clinical and psychopathological features of obsessive-compulsive disorder (OCD) in women with bipolar disorder (BD). METHODS Fifteen outpatients with concurrent bipolar disorder I (80.0%) or II (20.0%) and obsessive-compulsive disorder were studied. Most of them (80.0%) sought treatment for bipolar disorder. They were ascertained by means of the Structured Clinical Interview for DSM-IV (SCID/P), semi-structured interviews to investigate obsessions, compulsions and sensory phenomena that may precede compulsions and an additional module for the diagnosis of chronic motor and vocal tics. Severity of symptoms was assessed by the Yale-Brown Obsessive-Compulsive Rating Scale, Hamilton Depression Rating Scale and Young Mania Rating Scale. RESULTS Obsessive-compulsive disorder presented early onset (before the age of 10) in 9 (60%) cases, preceded bipolar disorder in 10 (66.7%) and displayed chronic waxing and waning course in 13 (86.7%) of them. There was wide overlap between types of obsessive-compulsive symptoms and all patients experienced sensory phenomena preceding the compulsions. There was no clear-cut impact of depressive and manic episodes on the intensity of obsessive-compulsive symptoms, which increased in depression and decreased in mania in 40.0% of the cases, had the opposite pattern in 26.7% of the patients and fluctuated inconsistently in the rest of them. Tics disorders were diagnosed in 5 (33.3%) patients. CONCLUSIONS Our results suggest that in women with comorbid bipolar disorder and obsessive-compulsive disorder the latter presents features that may be typical of the association of the two disorders, such as early onset and sensory phenomena preceding compulsions. A prospective controlled study is necessary to confirm these observations, due to some limitations of our study: small exclusively female sample, heterogeneity concerning the type of bipolar disorder and the disorder that determined sought of treatment and retrospective non-controlled design.

Obesity and metabolic syndrome in Brazilian patients with bipolar disorder.

Objective: We aimed to determine the prevalence of obesity and metabolic syndrome (O/MetS) in a sample of Brazilian outpatients with bipolar disorder. Methods: Eighty-four patients with bipolar disorder were evaluated. We used the definition of MetS established in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, modified by the American Heart Association (AHA). Patients were classified as obese if their body mass index (BMI) was ≥ 30 kg/m2. Results: We found that 28.6% of our sample met the AHA criteria for MetS and 35.7% were obese. The percentage of patients meeting each criterion of the AHA was as follows: 46% for abdominal obesity; 44% for hypertriglyceridemia or cholesterol-lowering medication use; 26% for low high-density lipoprotein cholesterol or being on a lipid-lowering medication; 45% for hypertension; and 20% for high fasting glucose or anti-diabetic medication use. Conclusions: The prevalence of obesity in our sample of outpatients with bipolar disorder was higher than that observed for the general population of Brazil. The rate of MetS was similar to that observed for the general population. Our data indicate the need for prevention, early detection and treatment of O/MetS in patients with bipolar disorder.

Bipolar disorder and comorbid obsessive-compulsive disorder is associated with higher rates of anxiety and impulse control disorders

Issler CK, Monkul ES, Amaral JAMS, Tamada RS, Shavitt RG, Miguel EC, Lafer B. Bipolar disorder and comorbid obsessive-compulsive disorder is associated with higher rates of anxiety and impulse control disorders. Objective: Although bipolar disorder (BD) with comorbid obsessive-compulsive disorder (OCD) is highly prevalent, few controlled studies have assessed this comorbidity. The objective of this study was to investigate the clinical characteristics and expression of comorbid disorders in female BD patients with OCD. Method: We assessed clinically stable female outpatients with BD: 15 with comorbid OCD (BD+OCD group) and 15 without (BD/no-OCD group). All were submitted to the Structured Clinical Interview for DSM-IV, with additional modules for the diagnosis of kleptomania, trichotillomania, pathological gambling, onychophagia and skin picking. Results: The BD+OCD patients presented more chronic episodes, residual symptoms and previous depressive episodes than the BD/no-OCD patients. Of the BD+OCD patients, 86% had a history of treatment-emergent mania, compared with only 40% of the BD/no-OCD patients. The following were more prevalent in the BD+OCD patients than the BD/no-OCD patients: any anxiety disorder other than OCD; impulse control disorders; eating disorders; and tic disorders. Conclusion: Female BD patients with OCD may represent a more severe form of disorder than those without OCD, having more depressive episodes and residual symptoms, and being at a higher risk for treatment-emergent mania, as well as presenting a greater anxiety and impulse control disorder burden.

Facial emotion recognition in euthymic patients with bipolar disorder and their unaffected first-degree relatives

BACKGROUND Facial emotion recognition (FER) is an important task associated with social cognition because facial expression is a significant source of non-verbal information that guides interpersonal relationships. Increasing evidence suggests that bipolar disorder (BD) patients present deficits in FER and these deficits may be present in individuals at high genetic risk for BD. The aim of this study was to evaluate the occurrence of FER deficits in euthymic BD patients, their first-degree relatives, and healthy controls (HC) and to consider if these deficits might be regarded as an endophenotype candidate for BD. METHODS We studied 23 patients with DSM-IV BD type I, 22 first-degree relatives of these patients, and 27 HC. We used the Penn Emotion Recognition Tests to evaluate tasks of FER, emotion discrimination, and emotional acuity. Patients were recruited from outpatient facilities at the Institute of Psychiatry of the University of Sao Paulo Medical School, or from the community through media advertisements, had to be euthymic, with age above 18years old and a diagnosis of DSM-IV BD type I. RESULTS Euthymic BD patients presented significantly fewer correct responses for fear, and significantly increased time to response to recognize happy faces when compared with HC, but not when compared with first-degree relatives. First-degree relatives did not significantly differ from HC on any of the emotion recognition tasks. CONCLUSION Our results suggest that deficits in FER are present in euthymic patients, but not in subjects at high genetic risk for BD. Thus, we have not found evidence to consider FER as an endophenotype candidate for BD.

Gray matter volumes in patients with bipolar disorder and their first-degree relatives

Bipolar disorder (BD) is highly heritable. First-degree relatives of BD patient have an increased risk to develop the disease. We investigated abnormalities in gray matter (GM) volumes in healthy first-degree relatives of BD patients to identify possible brain structural endophenotypes for the disorder. 3D T1-weighted magnetic resonance images were obtained from 25 DSM-IV BD type I patients, 23 unaffected relatives, and 27 healthy controls (HC). A voxel-based morphometry protocol was used to compare differences in GM volumes between groups. BD patients presented reduced GM volumes bilaterally in the thalamus compared with HC. Relatives presented no global or regional GM differences compared with HC. Our negative results do not support the role of GM volume abnormalities as endophenotypes for BD. Thalamic volume abnormalities may be associated the pathophysiology of the disease.

A clinical study comparing manic and mixed episodes in patients with bipolar disorder

OBJECTIVE Mixed episodes have been described as more severe than manic episodes, especially due to their longer duration and their association with higher rates of suicide attempts, hospitalization and psychotic symptoms. The purpose of this study was to compare the severity between mixed and pure manic episodes according to DSM-IV criteria, through the evaluation of sociodemographic data and clinical characteristics. METHOD Twenty-nine bipolar I patients presenting acute mixed episodes were compared to 20 bipolar I patients with acute manic episodes according to DSM-IV criteria. We analyzed (cross-sectionally) episode length, presence of psychotic symptoms, frequency of suicide attempts and hospitalization, Young Mania Rating Scale scores, Hamilton Depression Rating Scale scores and the Clinical Global Assessment Scale scores. RESULTS Young Mania Rating Scale scores were higher in manic episodes than in mixed episodes. There were no differences in gender frequency, CGI scores and rates of hospitalization, suicide attempts and psychotic symptoms, when mixed and manic episodes where compared. Patients with mixed episodes were younger. CONCLUSION In our sample, mixed states occurred at an earlier age than manic episodes. Contrary to previous reports, we did not find significant differences between manic and mixed episodes regarding severity of symptomatology, except for manic symptoms ratings, which were higher in acute manic patients. In part, this may be explained by the different criteria adopted on previous studies.

Serum BDNF levels in unaffected first-degree relatives of patients with bipolar disorder

Objective: Unaffected relatives of bipolar disorder (BD) patients have been investigated for the identification of endophenotypes in an attempt to further elucidate the pathophysiology of the disease. Brain-derived neurotrophic factor (BDNF) is considered to be implicated in the pathophysiology of BD, but its role as an endophenotype has been poorly studied. We investigated abnormal serum BDNF levels in BD patients, in their unaffected relatives, and in healthy controls. Methods: BDNF levels were obtained from 25 DSM-IV bipolar I disorder patients, 23 unaffected relatives, and 27 healthy controls. All BD patients were in remission. The unaffected subjects were first-degree relatives of the proband who had no lifetime DSM-IV diagnosis of axis I disorder. BDNF serum levels were determined by sandwich ELISA using monoclonal BDNF-specific antibodies. Results: There were no statistical differences in BDNF levels among BD patients, relatives, and healthy controls. Conclusion: Serum BDNF levels may not indicate high genetic risk for BD, possibly acting as state markers rather than trait markers of the disease.

Antidepressant treatment-emergent affective switch in bipolar disorder: a prospective case-control study of outcome

OBJECTIVE: Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse. METHOD: Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up. RESULTS: Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode). Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016). CONCLUSIONS: In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania.

Reply to Dr. Kauer-Sant'Anna and Dr. Yatham's letter "comment on 'Antidepressant treatment-emergent affective switch in bipolar disorder: a prospective case-control study of outcome'"

OBJECTIVE Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse. METHOD Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up. RESULTS Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode). Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016). CONCLUSIONS In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania.